Ignite Creation Date:
2024-05-06 @ 11:22 AM
Last Modification Date:
2024-10-26 @ 12:44 PM
Study NCT ID:
NCT03509532
Status:
UNKNOWN
Last Update Posted:
2018-04-26
First Post:
2018-04-17
Brief Title:
DRUG ELUTING STENT FOR DIABETIC PATIENTS IN CORONARY ARTERY DISEASE TREATMENT
Sponsor:
IRCCS Ospedale Galeazzi-SantAmbrogio
Organization:
IRCCS Ospedale Galeazzi-SantAmbrogio
Study Overview
Official Title:
A POST MARKET REGISTRY OF ABLUMINUS SIROLIMUS ELUTING CORONARY STENT SYSTEM FOR PERCUTANEOUS INTERVENTION IN PATIENTS WITH DIABETES MELLITUS
Status:
UNKNOWN
Status Verified Date:
2018-04
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DEDICATE
Brief Summary:
Study Title A post market registry of Abluminus sirolimus eluting coronary stent system for percutaneous intervention in patients with diabetes mellitus Purpose The purpose of this registry is to prospectively capture clinical data of ABLUMINUS sirolimus eluting stent in patients with Diabetes Mellitus
Investigational Device ABLUMINUS sirolimus eluting stent consists of four components a bare metal stent BMS a delivery system the bio absorbable polymer delivery matrix and Abluminal surface coating on stent and parts of balloon in Pre-crimped condition the anti-proliferative drug Sirolimus
Study Design Prospective Observational Multi-center registry Estimated Enrolment 1000 patients
End points Primary Endpoints
Target Lesion Failure that is composite of cardiac death target-vessel myocardial infarction and clinically indicated target lesion revascularisation within 12 months
Components of the primary end point are defined as follows
Cardiac Death any death due to immediate cardiac cause deaths related to the procedure unwitnessed death and death of unknown cause
Target Vessel Myocardial infarction categorised according to the Minnesota electrocardiographic criteria Q-wave and non-Q-wave Spontaneous myocardial infarction was defined as a typical rise and fall of creatinine kinase-MB fraction or troponin in the presence of at least one of several conditions ischaemic symptoms new pathological Q waves ischaemic electrocardiographic changes or pathological evidence of acute myocardial infarction Peri-procedural myocardial infarction was defined as an increase in creatinine kinase to more than twice the normal value with increased values of confirmatory biomarkers creatinine kinase-MB fraction or troponin higher than usual Target-vessel-related myocardial infarction was one related to the target vessel or that could not be clearly related to another vessel
Target Lesion Revascularisation any repeat percutaneous or surgical intervention due to a stenosis or occlusion within the device of the index procedure
Secondary Endpoints
Stent thrombosis Time Frame 1 month 12 months yearly Definite and probable stent thrombosis according to ARC definitions
Cardiac death Time Frame 1 month 12 months yearly
Target Vessel Myocardial infarction Time Frame 1 month 12 months yearly
Target Lesion Revascularisation Time Frame 1 month 12 months yearly
Device Success at 24 hours
Lesion Success at 24 hours
Procedural Success at 24 hours Eligibility Eligible Age 18 Years and older Eligible Genders Both Inclusion Criteria
The patient must be at least 18 years of age
Diabetic patient having clinical evidence of myocardial ischemia eg stable or unstable angina silent ischemia or positive functional study acute coronary syndromes will be considered
The patient is an acceptable candidate for percutaneous trans-luminal coronary angioplasty PTCA stenting and emergent coronary artery bypass graft CABG surgery
Culprit de novo lesion in a native coronary artery with significant stenosis 50 by visual estimate eligible for stent implantation no limitation on the number of treated lesions vessel and lesion length
Patients included are those for whom the physician has already considered worthwhile the use of Abluminus Stent according to the indications provided by the IFU
Patient provides written informed consent
Patient agrees to all required follow-up procedures and visits Exclusion Criteria The patient has a known hypersensitivity or contraindication to any of the following medicationsHeparin Aspirin Both Clopidogrel and TIclopidine Sirolimus paclitaxel ABT 578Stainless steel Cobalt biodegradable PLLA polymer
Patients with hypersensitivity to contrast media who cannot be treated with adequate prophylaxis
Female of childbearing potential unless a recent pregnancy test is negative who possibly plan to become pregnant any time after enrolment into this study
Patients who are actively participating in another drug or device investigational study which have not completed the primary endpoint follow-up period
History of bleeding diathesis or known coagulopathy including heparin-induced thrombocytopenia or will refuse blood transfusions
Previous coronary intervention on target vessel
Non-cardiac co-morbid conditions with life expectancy 1 year or that may result in protocol non-compliance per site investigators medical judgment
Lesions not allowing a complete balloon inflation or stent deployment Clinical Follow up At Discharge 1 month 6 months 12 months yearly
Investigational Device ABLUMINUS sirolimus eluting stent consists of four components a bare metal stent BMS a delivery system the bio absorbable polymer delivery matrix and Abluminal surface coating on stent and parts of balloon in Pre-crimped condition the anti-proliferative drug Sirolimus
Study Design Prospective Observational Multi-center registry Estimated Enrolment 1000 patients
End points Primary Endpoints
Target Lesion Failure that is composite of cardiac death target-vessel myocardial infarction and clinically indicated target lesion revascularisation within 12 months
Components of the primary end point are defined as follows
Cardiac Death any death due to immediate cardiac cause deaths related to the procedure unwitnessed death and death of unknown cause
Target Vessel Myocardial infarction categorised according to the Minnesota electrocardiographic criteria Q-wave and non-Q-wave Spontaneous myocardial infarction was defined as a typical rise and fall of creatinine kinase-MB fraction or troponin in the presence of at least one of several conditions ischaemic symptoms new pathological Q waves ischaemic electrocardiographic changes or pathological evidence of acute myocardial infarction Peri-procedural myocardial infarction was defined as an increase in creatinine kinase to more than twice the normal value with increased values of confirmatory biomarkers creatinine kinase-MB fraction or troponin higher than usual Target-vessel-related myocardial infarction was one related to the target vessel or that could not be clearly related to another vessel
Target Lesion Revascularisation any repeat percutaneous or surgical intervention due to a stenosis or occlusion within the device of the index procedure
Secondary Endpoints
Stent thrombosis Time Frame 1 month 12 months yearly Definite and probable stent thrombosis according to ARC definitions
Cardiac death Time Frame 1 month 12 months yearly
Target Vessel Myocardial infarction Time Frame 1 month 12 months yearly
Target Lesion Revascularisation Time Frame 1 month 12 months yearly
Device Success at 24 hours
Lesion Success at 24 hours
Procedural Success at 24 hours Eligibility Eligible Age 18 Years and older Eligible Genders Both Inclusion Criteria
The patient must be at least 18 years of age
Diabetic patient having clinical evidence of myocardial ischemia eg stable or unstable angina silent ischemia or positive functional study acute coronary syndromes will be considered
The patient is an acceptable candidate for percutaneous trans-luminal coronary angioplasty PTCA stenting and emergent coronary artery bypass graft CABG surgery
Culprit de novo lesion in a native coronary artery with significant stenosis 50 by visual estimate eligible for stent implantation no limitation on the number of treated lesions vessel and lesion length
Patients included are those for whom the physician has already considered worthwhile the use of Abluminus Stent according to the indications provided by the IFU
Patient provides written informed consent
Patient agrees to all required follow-up procedures and visits Exclusion Criteria The patient has a known hypersensitivity or contraindication to any of the following medicationsHeparin Aspirin Both Clopidogrel and TIclopidine Sirolimus paclitaxel ABT 578Stainless steel Cobalt biodegradable PLLA polymer
Patients with hypersensitivity to contrast media who cannot be treated with adequate prophylaxis
Female of childbearing potential unless a recent pregnancy test is negative who possibly plan to become pregnant any time after enrolment into this study
Patients who are actively participating in another drug or device investigational study which have not completed the primary endpoint follow-up period
History of bleeding diathesis or known coagulopathy including heparin-induced thrombocytopenia or will refuse blood transfusions
Previous coronary intervention on target vessel
Non-cardiac co-morbid conditions with life expectancy 1 year or that may result in protocol non-compliance per site investigators medical judgment
Lesions not allowing a complete balloon inflation or stent deployment Clinical Follow up At Discharge 1 month 6 months 12 months yearly
Detailed Description:
DEDICATE Registry
DRUG ELUTING STENT FOR DIABETIC PATIENTS IN CORONARY ARTERY DISEASE TREATMENT
A POST MARKET REGISTRY OF ABLUMINUS SIROLIMUS ELUTING CORONARY STENT SYSTEM FOR PERCUTANEOUS INTERVENTION IN PATIENTS WITH DIABETES MELLITUS
Version 10
Principal Investigator Dr Luca Testa MD PhD Head of Coronary Revascularization Unit Head of Clinical Research Unit Department of Cardiology IRCCS Policlinico S Donato San Donato Mne Milan Italy Email luctesgmailcom
Chairperson Dr Francesco Bedogni MD Head of Cardiology IRCCS Policlinico S Donato San Donato Mne Milan Italy
Protocol Signature Page
Principal Investigator Coordinator Center
Investigate site IRCCS Policlinico San Donato
Name Dr Luca Testa
Signature ______________________
Date _____________________
Chairperson Coordinator Center
Investigate site IRCCS Policlinico San Donato
Name Dr Francesco Bedogni
Signature ______________________
Date _____________________
Principal Investigator
Investigate site ___________________
Name __________________
Signature ______________________
Date _____________________
Protocol summary
Study Title A post market registry of Abluminus sirolimus eluting coronary stent system for percutaneous intervention in patients with diabetes mellitus Purpose The purpose of this registry is to prospectively capture clinical data of ABLUMINUS sirolimus eluting stent in patients with Diabetes Mellitus
Investigational Device ABLUMINUS sirolimus eluting stent consists of four components a bare metal stent BMS a delivery system the bio absorbable polymer delivery matrix and Abluminal surface coating on stent and parts of balloon in Pre-crimped condition the anti-proliferative drug Sirolimus
Study Design Prospective Observational Multi-center registry Estimated Enrolment 1000 patients
End points Primary Endpoints
Target Lesion Failure that is composite of cardiac death target-vessel myocardial infarction and clinically indicated target lesion revascularisation within 12 months
Components of the primary end point are defined as follows
Cardiac Death any death due to immediate cardiac cause deaths related to the procedure unwitnessed death and death of unknown cause
Target Vessel Myocardial infarction categorised according to the Minnesota electrocardiographic criteria Q-wave and non-Q-wave Spontaneous myocardial infarction was defined as a typical rise and fall of creatinine kinase-MB fraction or troponin in the presence of at least one of several conditions ischaemic symptoms new pathological Q waves ischaemic electrocardiographic changes or pathological evidence of acute myocardial infarction Peri-procedural myocardial infarction was defined as an increase in creatinine kinase to more than twice the normal value with increased values of confirmatory biomarkers creatinine kinase-MB fraction or troponin higher than usual Target-vessel-related myocardial infarction was one related to the target vessel or that could not be clearly related to another vessel
Target Lesion Revascularisation any repeat percutaneous or surgical intervention due to a stenosis or occlusion within the device of the index procedure
Secondary Endpoints
Stent thrombosis Time Frame 1 month 12 months yearly Definite and probable stent thrombosis according to ARC definitions
Cardiac death Time Frame 1 month 12 months yearly
Target Vessel Myocardial infarction Time Frame 1 month 12 months yearly
Target Lesion Revascularisation Time Frame 1 month 12 months yearly
Device Success at 24 hours
Lesion Success at 24 hours
Procedural Success at 24 hours Eligibility Eligible Age 18 Years and older Eligible Genders Both Inclusion Criteria
The patient must be at least 18 years of age
Diabetic patient having clinical evidence of myocardial ischemia eg stable or unstable angina silent ischemia or positive functional study acute coronary syndromes will be considered
The patient is an acceptable candidate for percutaneous trans-luminal coronary angioplasty PTCA stenting and emergent coronary artery bypass graft CABG surgery
Culprit de novo lesion in a native coronary artery with significant stenosis 50 by visual estimate eligible for stent implantation no limitation on the number of treated lesions vessel and lesion length
Patients included are those for whom the physician has already considered worthwhile the use of Abluminus Stent according to the indications provided by the IFU
Patient provides written informed consent
Patient agrees to all required follow-up procedures and visits Exclusion Criteria The patient has a known hypersensitivity or contraindication to any of the following medicationsHeparin Aspirin Both Clopidogrel and TIclopidine Sirolimus paclitaxel ABT 578Stainless steel Cobalt biodegradable PLLA polymer
Patients with hypersensitivity to contrast media who cannot be treated with adequate prophylaxis
Female of childbearing potential unless a recent pregnancy test is negative who possibly plan to become pregnant any time after enrolment into this study
Patients who are actively participating in another drug or device investigational study which have not completed the primary endpoint follow-up period
History of bleeding diathesis or known coagulopathy including heparin-induced thrombocytopenia or will refuse blood transfusions
Previous coronary intervention on target vessel
Non-cardiac co-morbid conditions with life expectancy 1 year or that may result in protocol non-compliance per site investigators medical judgment
Lesions not allowing a complete balloon inflation or stent deployment Clinical Follow up At Discharge 1 month 6 months 12 months yearly
CONTENTS
1 BACKGROUND AND INTRODUCTION 7
2 RISK ANALYSIS 9
3 AIM OF THE REGISTRY 11
4 REGISTRY DESIGN 11
5 ENDPOINT 11
6 REGISTRY POPULATION 12
7 REGISTRY PROCEDURES 13
8 ANTITHROMBOTIC TREATMENT 14
9 FOLLOW-UP PERIOD 15
10 SERIOUS ADVERSE EVENT REPORTING 15
11 MACE ADJUDICATION 16
12 STATISTICAL ANALYSIS 16
13 QUALITY CONTROL AND ASSURANCE 16
14 ETHICAL CONSIDERATION 17
-- --
1 BACKGROUND AND INTRODUCTION
Era of Percutaneous Coronary Intervention PCI started with plain old balloon angioplasty POBA and progressed to bare metal stent BMS and then to drug-eluting stent DES In DES polymer was used in addition to the drug so that it could hold the drug on the stent platform and could facilitate controlled drug release Thus drug and polymer became hallmark of DES 1
Current DES consist of a metal stent platform and a therapeutic agent which is either directly immobilized on the stent surface or released from a polymer matrix While drug-eluting stents without surface polymer are available the reduction in angiographic and clinical restenosis is less potent and appears therefore less promising for clinical utilization In contrast polymer-based drug-eluting stents allow for controlled release of therapeutic agents at the site of injury 2
The most effective drugs utilized with drug-eluting stents for prevention of restenosis up to this point in time have been Sirolimus and Paclitaxel Both drugs are highly lipophilic and show rapid and strong uptake in arterial wall tissue In addition Sirolimus and paclitaxel have been shown to reduce smooth muscle cell proliferation and neo-intimal hyperplasia the principal cause of restenosis after coronary stenting in experimental models Sirolimus and Paclitaxel have the same effect on cells proliferation but with a different mode of actionA recent meta-analysis of drug-eluting stent trials confirmed the reduction in restenosis and repeat revascularization procedures for polymer-based drug-eluting stents Moreover the rates of death and myocardial infarction were comparable to those with bare-metal stents attesting to the safety of these devices which have been approved by the US Food and Drug Administration
Patients with diabetes mellitus referred for percutaneous coronary intervention PCI represent one of the greatest challenges for the interventional cardiologist Restenosis continues to be the major limitation of PCI particularly in patients with diabetes 2 Restenosis rates after balloon angioplasty in diabetic patients can be very high up to 63 and although stenting has been shown to decrease these rates diabetic patients continue to have significantly higher restenosis rates and clinical events following PCI Slight elevations in fasting blood glucose levels the need for insulin and suboptimal blood glucose control may have a significant impact on the prognosis Drug-eluting stents DES have been shown to have a considerably lower risk of restenosis and as a result there is growing interest in using such stents to treat coronary lesions in complex scenarios Sub studies carried out in diabetic patients from large clinical trials conducted with DES have found considerable decreases in the risk of restenosis and new revascularizations 34 Nevertheless despite the availability use of DES diabetic patients show a higher risk than non-diabeticsHyperinsulinemia and insulin resistance are implicated in a variety of molecular mechanisms that could predispose diabetics to a higher incidence of restenosis
The purpose of this registry is to capture clinical data of ABLUMINUS sirolimus eluting stent in in real world all come patients with Diabetes Mellitus
11 Device Description
The device ABLUMINUS Sirolimus eluting coronary stent integrates well known and accepted Sirolimus drug on the proven CYGNUS Cobalt chromium platform with biodegradable polymer matrix
The device ABLUMINUS sirolimus eluting stent system has a combination of inactive and active component The active component is Sirolimus drug The inactive component is PLLA polymer biodegradable polymer The polymer-drug combination is applied solely to a unique abluminal coating technology known as ënvisõlution Technology which is a highly effective drug delivery technology with target specific coating in abluminal configuration on stent and parts of balloon It also uses biodegradable polymer to achieve longer drug release
The stent platform is a thin strut 73 microns of L605cobalt chromium stent with open and closed cell hybrid design which provides good radial strength and side branch accessibility The thin struts enhance the trackability and gives lower crossing profile to the device for navigating through difficult and tortuous lesions The delivery system is a Rapid exchange Rx System
It is expected that ABLUMINUS sirolimus eluting stent system will significantly reduce delay in healing and thrombosis events while providing comparable results regarding restenosis to other DES systems on the market
12 Therapeutic Agent-Sirolimus Drug
Sirolimus is a cytostatic drug used for treatment of various disease in Humans The drug works on FKBP-12 protein and inhibits growth factor-simulated cell proliferation Sirolimus forms a complex with FKBP Protein that inhibits the cell cycle between G0 and G1 phase This results in interruption of the cascade governing cell growth metabolism and proliferation
13 STENT PLATFORM ABLUMINUS sirolimus eluting stent system is a combination product comprised of two key components the Stent which includes the active pharmaceutical ingredient API Sirolimus drug incorporated into a bio-degradable polymer coating and delivery catheter A balloon expandable L605 chromium cobalt stent with bio-degradable polymer coating containing Sirolimus drug is pre-mounted onto a highly deliverable semi-compliant rapid exchange delivery system The delivery catheter has two radiopaque markers which mark the ends of the stent to facilitate proper positioning and placement The catheter has hydrophilic coating facilitating easy delivery of the system
The Stent has a biodegradable polymer matrix consisting of Poly L Lactic acid PLLA which has been wide spread application in medical devices The Poly lactic acid its co-polymers and mixtures have been evaluated in pre-clinical studies and clinical studies around the world revealing favourable bio-compatibility profile The bio-degradable polymer has been demonstrated to be safe when used as an implant or drug release-control polymer for both animal and humans
2 RISK ANALYSIS
As with any patient undergoing percutaneous coronary intervention subject in this registry may experience adverse events andor outcomes that may include but are not necessarily limited to the following
Abrupt stent closure or failure to expand the stent
Abrupt vessel closure or spasm
Acute myocardial infarction
Allergic reaction to anti-coagulation andor anti thrombotic therapy contrast material or stent andor delivery system materials
Aneurysm pseudo aneurysm or arteriovenous fistula
Arrhythmias including ventricular fibrillation and ventricular tachycardia
Cardiac tamponade
Cardiogenic shock
Death
Dissection perforation or rupture of the coronary artery
Emboli distal air tissue or thrombic emboli
Emergency coronary artery bypass graft CABG as a result of damage to the stent injury to the vessel
Fever
Hematoma at insertion site
Haemorrhage requiring transfusion
Hypotensionhypertension
Infection andor pain at site of insertion
Late stent thrombosis stent thrombosis occlusion
Perforation or rupture of artery
Peripheral ischemia or peripheral nerve injury
Stroke or transient ischemia attack
Renal failure
Restenosis of stented segment
Stent migration or stent embolization
Total occlusion of coronary artery
Unstable angina
Adverse events that may be associated with Sirolimus drug coating
Allergicimmunologic reaction to drug or stent coating
Alopecia
Anaemia
Blood product transfusion
Gastrointestinal symptoms
Haematologicaldyscrasia including leukopenia neutropenia thrombocytopenia
Hepatic enzyme changes
Histological changes in vessel wall including inflammation cellular damage or necrosis
MyalgiaArthralgia
Peripheral neuropathy
Appropriate contraindications and warnings are also included in the instructions for use provided with the device Interventional cardiologists are invited to participate as investigators in this registry All clinicians will have experience with the treatment and control procedures and have been trained on the use implantation of a Drug Eluting stent system
3 AIM OF THE REGISTRY
The purpose of this registry is to capture clinical data of ABLUMINUS sirolimus eluting stent in real world all comer patients with Diabetes Mellitus
4 REGISTRY DESIGN
Prospective Observational Multi-center clinical registry to be conducted in Italy at 15 Interventional cardiology centers 1000 patients will be enrolled and evaluated All the patients will be followed up for up to 5 years
41 Treatment Strategy
The investigator will determine the treatment strategy It is recommended that each enrolling investigator review the most recent IFU to assess contraindications warnings and precautions for treating potential patients
5 ENDPOINT
51 Primary endpoints
Target Lesion Failure which is composite of cardiac death target-vessel myocardial infarction and clinically indicated target lesion revascularisation within 12 months
Components of the primary end point are defined as follows
Cardiac Death any death due to immediate cardiac cause deaths related to the procedure unwitnessed death and death of unknown cause
Target Vessel Myocardial infarction categorized according to the Minnesota electrocardiographic criteria Q-wave and non-Q-wave Spontaneous myocardial infarction was defined as a typical rise and fall of creatinine kinase-MB fraction or troponin in the presence of at least one of several conditions ischemic symptoms new pathological Q waves ischemic electrocardiographic changes or pathological evidence of acute myocardial infarction Peri-procedural myocardial infarction was defined as an increase in creatinine kinase to more than twice the normal value with increased values of confirmatory biomarkers creatinine kinase-MB fraction or troponin higher than usual Target-vessel-related myocardial infarction was one related to the target vessel or that could not be clearly related to another vessel
Clinically indicated target lesion revascularisation any repeat percutaneous or surgical intervention due to a stenosis or occlusion within the device of the index procedure 52 Secondary endpoints
Stent thrombosis Time Frame 1 month 12 months yearly Definite and probable stent thrombosis according to ARC definitions
Cardiac death Time Frame 1 month 12 months yearly
Target Vessel Myocardial infarction Time Frame 1 month 12 months yearly
Target Lesion Revascularisation Time Frame 1 month 12 months yearly
Device Success at 24 hours
Lesion Success at 24 hours
Procedural Success at 24 hours
6 REGISTRY POPULATION
61 Number of patients 1000 patients will be enrolled at 15 interventional cardiology sites in Italy Duration of enrollment will be 12 months
62 Type of Patient Patients eligible for PCI Percutaneous Coronary Intervention with lesions suitable for stent implantation and having diabetes Mellitus will be included according to the inclusion and exclusion criteria specified below The inclusion criteria will be kept comprehensive to reflect routine clinical practice of treatment Real world Scenario-All comer patients
1 Inclusion Criteria
1 The patient must be at least 18 years of age 2 Diabetic patient having clinical evidence of myocardial ischemia eg stable or unstable angina silent ischemia or positive functional study acute coronary syndromes will be considered
3 The patient is an acceptable candidate for percutaneous trans luminal coronary angioplasty PTCAstenting and emergent coronary artery bypass graft CABG surgery
4 Culprit de novo lesion in a native coronary artery with significant stenosis 50 by visual estimate eligible for stent implantation no limitation on the number of treated lesions vessel and lesion length 5 Patients included are those for whom the physician has already considered worthwhile the use of Abluminus Stent according to the indications provided by the IFU 6 Patient provides written informed consent 7 Patient agrees to all required follow-up procedures and visits
2 Exclusion Criteria
1 The patient has a known hypersensitivity or contraindication to any of the following medications Heparin Aspirin Both Clopidogrel and Ticlopidine Sirolimus Paclitaxel ABT 578 Stainless steel Chromium Cobalt biodegradable PLLA polymer
2 Patients with hypersensitivity to contrast media who cannot be treated with adequate prophylaxis
3 Female of childbearing potential unless a recent pregnancy test is negative who possibly plan to become pregnant any time after enrollment into this study
4 History of bleeding diathesis or known coagulopathy including heparin-induced thrombocytopenia or will refuse blood transfusions
5 Patients who are actively participating in another drug or device investigational study which have not completed the primary endpoint follow-up period
6 Previous coronary intervention on target vessel
7 Non-cardiac co-morbid conditions are present with life expectancy 1 year or that may result in protocol non-compliance per site investigators medical judgment
8 Lesions not allowing a complete balloon inflation or stent deployment
7 REGISTRY PROCEDURES
71 Patient Information
Eligible patients will be informed about the registry and have to sign informed consent before or after the procedure see Appendix I informed consent form
72 Baseline Evaluation
At inclusion into registry the following routine examination if performed will be captured
1 Physical examination and relevant medical history 2 Angina status 3 Routine laboratory tests including complete blood count CBC blood chemistry blood sugar and lipids CK andor CK-MB prior to the procedure In case of acute myocardial infarction or infarct extension we suggest CK andor CK-MB immediately prior to the procedure and serial measurements every 8 hours after the procedure until the peak CK level has been defined 4 12-lead electrocardiogram before the procedure
73 Stent Implantation
During the index procedure only ABLUMINUS sirolimus eluting stent system will be implanted Using the instruction for use IFU provided with the device the investigator will choose the appropriate length and diameter of the stents to be implanted by visual estimation
The choice of the length of the stent should ensure complete coverage of the lesion If more than one stent is implanted at least 2 mm overlap should be achieved In case of insufficient stent expansion the stent will be post-dilated with an appropriately sized balloon
Treatment of multiple target vessels within the same procedure and staged procedures which occur within 90 days of the initial implant procedure are allowed ABLUMINUS sirolimus eluting stent system implanted in non-target vessels after 90 days after the initial implant procedure will not be followed under the ABLUMINUS sirolimus eluting stent system registry protocol
As such any subsequent treatment of the lesion already present at the time of baseline procedure will be considered as a staged procedure instead of a repeat PCI In the CRF Case Report Form the investigator will complete a staged procedure module indicating that this lesion was present at the time of first procedure The lesions diagnosed and treated at the later stages will not be considered as repeat revascularization
For each individual lesion treated a separate lesion form in the CRF needs to be completed Every vessel in which anABLUMINUS sirolimus eluting stent system is implanted or in which an attempt to implant anABLUMINUS sirolimus eluting stent system is made within 90 days of the initial implant procedure is considered a target vessel
For patient undergoing a staged procedure the follow up schedule will be calculated from the date of initial ABLUMINUS sirolimus eluting stent system implant procedure
8 ANTITHROMBOTIC TREATMENT
Pre- procedure Aspirin 75mg minimum
Patients without any therapy clopidogrel bisulphate loading dose of 300-600mg per os before or during the procedure
Patient on clopidogrel therapy within 7 days prior no loading dose required
Ticagrelor or Prasugrel in the case of Acute Coronary Syndromes
During Procedure At least 5000IE or 70-100IEKg unfractioned heparin to maintain an ACT 250 seconds during the procedure
Post-procedure DAPT Therapy for at least 6 months IFU or longer according to current Guidelines Aspirin 75mg per os life long
Or according to standard clinical practice The use of GP IIB IIIA inhibitors is left to the discretion of the operator
9 FOLLOW-UP PERIOD
Patients will be followed after hospital discharge up to 5 years after the index procedure This includes telephone contacts to obtain information regarding medical history cardiovascular drug use hospitalizations and adverse events at 1 month 6 months 12 months and then yearly post procedure Apart from clinical follow -ups there is angiographic follow-up which is clinically driven symptom driven
10 SERIOUS ADVERSE EVENT REPORTING
101 Serious Adverse Events SAEs
An adverse event AE is report as serious which lead to
Death
Life-threatening illness or injury or
Permanent impairment of a body structure or a body function or
In-patient or prolonged hospitalization see note below or
Medical or surgical intervention to prevent life-threatening illness or injury or permanent impairment to a body structure or a body function
Note For the purposes of this study in-patient hospitalization is defined as the subject being admitted to the hospital with the exception of any planned hospitalization for a pre-existing condition or a procedure required by the local standard of care which do not have to be reported as an SAE
All serious adverse events must be reported to the Principal Investigator within 24 hours of discovery or notification of the event and to the local EC as per local requirements
The Principal Investigator is responsible for reporting adequate information on SAEs that may be related to the study device to the regulatory authorities per countrys applicable reporting requirements
102 Unanticipated Serious Adverse Device Effect USADE
Any serious adverse effect on the health or safety or any life-threatening problem or death caused by or associated with a device if that effect problem or death was not previously identified in nature severity or degree of incidence in the investigational plan or application including a supplementary plan or application or any other unanticipated serious problem associated with a device that relates to the rights safety or welfare of subjects
Unanticipated Adverse Device Effects must be reported to the manufacturer as soon as possible following the standard vigilance route Reporting the event ONLY in the CRF is not an option
11 MACE ADJUDICATION
All registry devices related Major Adverse Cardiac Events MACE will be reviewed classified by the treating physician In case of a stent thrombosis or severe stent restenosis these events will verify the stent thrombosis determine the Diameter Stenosis DS by QCA
12 STATISTICAL ANALYSIS
121 Analysis Population All patients who are successfully registered will be included in the analysis
122 Sample Size Calculations and Assumptions Being this an observational registry aiming at quantifying effect estimates without direct comparisons to literature benchmarks we proceeded without a formal power analysis As the main analysis is a pooled analysis of all included patients an overall and comprehensive analysis is planned as the primary analytical approach to reflect real-world patients and practice
123 Statistical Analyses Continuous endpoints will be summarized by presenting the total number of patients mean standard deviation median minimum and maximum Tabulation of categorical parameters will include counts and percentages Survival analysis will be performed with the Kaplan-Meier method Statistical inference will be based on the computation of 95 confidence intervals using the adjusted Wald method Additional analyses will involve key subgroups defined according to baseline and procedural features with statistical significance set at the 5 2-tailed level Specifically Student t Fisher exact and log-rank tests will be used for such bivariate analyses whereas multivariable linear regression logistic regression and Cox proportional hazard analyses will be used to adjust for confounders
13 QUALITY CONTROL AND ASSURANCE
131 Quality Assurance The Principal Investigator of the Centre is responsible for the overall clinical management of patients admitted to his center and assumes global responsibilities for him and his staff and the data obtained from study participants he ensures compliance with the protocol laws and regulations ensures informed consent to be signed and that the CRF is accurate and complete
In accordance with Italian law and the ICHGCP guidelines the investigators and the institution will allow representatives of regulatory agencies and Ethics Committee direct access for review of the original documentation of patients to verify compliance with the procedures and the veracity of the data
132 Source Data The investigator assures that medical files are appropriately stored and completed Each follow up contact will be reported in the source data should at least contain the information collected by the registry The investigator assures that medical files and case record forms are accessible for inspection by Competent Authorities
133 Monitoring The study will be performed according to good clinical practice The collection of personal procedural and clinical data of patients must take place into the electronic CRF to which will only have access the individual investigators and the study principal investigator Dr Luca Testa as administrator
134 Publication policy All study investigators are committed to publishing the results at both conferences and international journals The PI of the study will have the right to present the main results before other investigators and will be the owner of the data After obtaining the consent of the PI the other experimenters will publish and present the full or partial results of the study
All investigators undertake to publish the study results whether they are positive negative or unexpected
14 ETHICAL CONSIDERATION
141 General Guidelines This registry will be conducted in accordance with ICH- GCP Good Clinical Practices The registry will be performed in accordance with the Declaration of Helsinki and ISO 141552011 and MED DEV 271 rev 3
142 Ethics Committee The protocol informed consent form and other registry-related documents will be submitted to the Institutional or Local Ethics Committee if applicable or are required for approval to initiate
143 Informed Consent A signed Informed Consent sample attached must be obtained before enrolment Importantly patients participation in the study is voluntary thus they may decide to terminate their involvement at any time by withdrawing consent
Bibliography
1 Stefanini GG Holmes DR Jr Drug-eluting coronary-artery stents N Engl J Med 2013368254-65
2 Serruys PW HE Luijten KJ Beatt et al Incidence of restenosis after successful coronary angioplasty a time-related phenomenon A quantitative angiographic study in 342 consecutive patients at 1 2 3 and 4 months Circulation 1988772361-371
3 Fihn SD Blankenship JC Alexander KP et al 2014 ACCAHAAATSPCNASCAISTS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease a report of the American College of CardiologyAmerican Heart Association Task Force on Practice Guidelines and the American Association for Thoracic Surgery Preventive Cardiovascular Nurses Association Society for Cardiovascular Angiography and Interventions and Society of Thoracic Surgeons J Am Coll Cardiol 2014 641929-49
4 Windecker S Kolh P Alfonso F et al 2014 ESCEACTS Guidelines on myocardial revascularization The Task Force on Myocardial Revascularization of the European Society of Cardiology ESC and the European Association for Cardio-Thoracic Surgery EACTS developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions EAPCI Eur Heart J 2014 352541-619
DRUG ELUTING STENT FOR DIABETIC PATIENTS IN CORONARY ARTERY DISEASE TREATMENT
A POST MARKET REGISTRY OF ABLUMINUS SIROLIMUS ELUTING CORONARY STENT SYSTEM FOR PERCUTANEOUS INTERVENTION IN PATIENTS WITH DIABETES MELLITUS
Version 10
Principal Investigator Dr Luca Testa MD PhD Head of Coronary Revascularization Unit Head of Clinical Research Unit Department of Cardiology IRCCS Policlinico S Donato San Donato Mne Milan Italy Email luctesgmailcom
Chairperson Dr Francesco Bedogni MD Head of Cardiology IRCCS Policlinico S Donato San Donato Mne Milan Italy
Protocol Signature Page
Principal Investigator Coordinator Center
Investigate site IRCCS Policlinico San Donato
Name Dr Luca Testa
Signature ______________________
Date _____________________
Chairperson Coordinator Center
Investigate site IRCCS Policlinico San Donato
Name Dr Francesco Bedogni
Signature ______________________
Date _____________________
Principal Investigator
Investigate site ___________________
Name __________________
Signature ______________________
Date _____________________
Protocol summary
Study Title A post market registry of Abluminus sirolimus eluting coronary stent system for percutaneous intervention in patients with diabetes mellitus Purpose The purpose of this registry is to prospectively capture clinical data of ABLUMINUS sirolimus eluting stent in patients with Diabetes Mellitus
Investigational Device ABLUMINUS sirolimus eluting stent consists of four components a bare metal stent BMS a delivery system the bio absorbable polymer delivery matrix and Abluminal surface coating on stent and parts of balloon in Pre-crimped condition the anti-proliferative drug Sirolimus
Study Design Prospective Observational Multi-center registry Estimated Enrolment 1000 patients
End points Primary Endpoints
Target Lesion Failure that is composite of cardiac death target-vessel myocardial infarction and clinically indicated target lesion revascularisation within 12 months
Components of the primary end point are defined as follows
Cardiac Death any death due to immediate cardiac cause deaths related to the procedure unwitnessed death and death of unknown cause
Target Vessel Myocardial infarction categorised according to the Minnesota electrocardiographic criteria Q-wave and non-Q-wave Spontaneous myocardial infarction was defined as a typical rise and fall of creatinine kinase-MB fraction or troponin in the presence of at least one of several conditions ischaemic symptoms new pathological Q waves ischaemic electrocardiographic changes or pathological evidence of acute myocardial infarction Peri-procedural myocardial infarction was defined as an increase in creatinine kinase to more than twice the normal value with increased values of confirmatory biomarkers creatinine kinase-MB fraction or troponin higher than usual Target-vessel-related myocardial infarction was one related to the target vessel or that could not be clearly related to another vessel
Target Lesion Revascularisation any repeat percutaneous or surgical intervention due to a stenosis or occlusion within the device of the index procedure
Secondary Endpoints
Stent thrombosis Time Frame 1 month 12 months yearly Definite and probable stent thrombosis according to ARC definitions
Cardiac death Time Frame 1 month 12 months yearly
Target Vessel Myocardial infarction Time Frame 1 month 12 months yearly
Target Lesion Revascularisation Time Frame 1 month 12 months yearly
Device Success at 24 hours
Lesion Success at 24 hours
Procedural Success at 24 hours Eligibility Eligible Age 18 Years and older Eligible Genders Both Inclusion Criteria
The patient must be at least 18 years of age
Diabetic patient having clinical evidence of myocardial ischemia eg stable or unstable angina silent ischemia or positive functional study acute coronary syndromes will be considered
The patient is an acceptable candidate for percutaneous trans-luminal coronary angioplasty PTCA stenting and emergent coronary artery bypass graft CABG surgery
Culprit de novo lesion in a native coronary artery with significant stenosis 50 by visual estimate eligible for stent implantation no limitation on the number of treated lesions vessel and lesion length
Patients included are those for whom the physician has already considered worthwhile the use of Abluminus Stent according to the indications provided by the IFU
Patient provides written informed consent
Patient agrees to all required follow-up procedures and visits Exclusion Criteria The patient has a known hypersensitivity or contraindication to any of the following medicationsHeparin Aspirin Both Clopidogrel and TIclopidine Sirolimus paclitaxel ABT 578Stainless steel Cobalt biodegradable PLLA polymer
Patients with hypersensitivity to contrast media who cannot be treated with adequate prophylaxis
Female of childbearing potential unless a recent pregnancy test is negative who possibly plan to become pregnant any time after enrolment into this study
Patients who are actively participating in another drug or device investigational study which have not completed the primary endpoint follow-up period
History of bleeding diathesis or known coagulopathy including heparin-induced thrombocytopenia or will refuse blood transfusions
Previous coronary intervention on target vessel
Non-cardiac co-morbid conditions with life expectancy 1 year or that may result in protocol non-compliance per site investigators medical judgment
Lesions not allowing a complete balloon inflation or stent deployment Clinical Follow up At Discharge 1 month 6 months 12 months yearly
CONTENTS
1 BACKGROUND AND INTRODUCTION 7
2 RISK ANALYSIS 9
3 AIM OF THE REGISTRY 11
4 REGISTRY DESIGN 11
5 ENDPOINT 11
6 REGISTRY POPULATION 12
7 REGISTRY PROCEDURES 13
8 ANTITHROMBOTIC TREATMENT 14
9 FOLLOW-UP PERIOD 15
10 SERIOUS ADVERSE EVENT REPORTING 15
11 MACE ADJUDICATION 16
12 STATISTICAL ANALYSIS 16
13 QUALITY CONTROL AND ASSURANCE 16
14 ETHICAL CONSIDERATION 17
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1 BACKGROUND AND INTRODUCTION
Era of Percutaneous Coronary Intervention PCI started with plain old balloon angioplasty POBA and progressed to bare metal stent BMS and then to drug-eluting stent DES In DES polymer was used in addition to the drug so that it could hold the drug on the stent platform and could facilitate controlled drug release Thus drug and polymer became hallmark of DES 1
Current DES consist of a metal stent platform and a therapeutic agent which is either directly immobilized on the stent surface or released from a polymer matrix While drug-eluting stents without surface polymer are available the reduction in angiographic and clinical restenosis is less potent and appears therefore less promising for clinical utilization In contrast polymer-based drug-eluting stents allow for controlled release of therapeutic agents at the site of injury 2
The most effective drugs utilized with drug-eluting stents for prevention of restenosis up to this point in time have been Sirolimus and Paclitaxel Both drugs are highly lipophilic and show rapid and strong uptake in arterial wall tissue In addition Sirolimus and paclitaxel have been shown to reduce smooth muscle cell proliferation and neo-intimal hyperplasia the principal cause of restenosis after coronary stenting in experimental models Sirolimus and Paclitaxel have the same effect on cells proliferation but with a different mode of actionA recent meta-analysis of drug-eluting stent trials confirmed the reduction in restenosis and repeat revascularization procedures for polymer-based drug-eluting stents Moreover the rates of death and myocardial infarction were comparable to those with bare-metal stents attesting to the safety of these devices which have been approved by the US Food and Drug Administration
Patients with diabetes mellitus referred for percutaneous coronary intervention PCI represent one of the greatest challenges for the interventional cardiologist Restenosis continues to be the major limitation of PCI particularly in patients with diabetes 2 Restenosis rates after balloon angioplasty in diabetic patients can be very high up to 63 and although stenting has been shown to decrease these rates diabetic patients continue to have significantly higher restenosis rates and clinical events following PCI Slight elevations in fasting blood glucose levels the need for insulin and suboptimal blood glucose control may have a significant impact on the prognosis Drug-eluting stents DES have been shown to have a considerably lower risk of restenosis and as a result there is growing interest in using such stents to treat coronary lesions in complex scenarios Sub studies carried out in diabetic patients from large clinical trials conducted with DES have found considerable decreases in the risk of restenosis and new revascularizations 34 Nevertheless despite the availability use of DES diabetic patients show a higher risk than non-diabeticsHyperinsulinemia and insulin resistance are implicated in a variety of molecular mechanisms that could predispose diabetics to a higher incidence of restenosis
The purpose of this registry is to capture clinical data of ABLUMINUS sirolimus eluting stent in in real world all come patients with Diabetes Mellitus
11 Device Description
The device ABLUMINUS Sirolimus eluting coronary stent integrates well known and accepted Sirolimus drug on the proven CYGNUS Cobalt chromium platform with biodegradable polymer matrix
The device ABLUMINUS sirolimus eluting stent system has a combination of inactive and active component The active component is Sirolimus drug The inactive component is PLLA polymer biodegradable polymer The polymer-drug combination is applied solely to a unique abluminal coating technology known as ënvisõlution Technology which is a highly effective drug delivery technology with target specific coating in abluminal configuration on stent and parts of balloon It also uses biodegradable polymer to achieve longer drug release
The stent platform is a thin strut 73 microns of L605cobalt chromium stent with open and closed cell hybrid design which provides good radial strength and side branch accessibility The thin struts enhance the trackability and gives lower crossing profile to the device for navigating through difficult and tortuous lesions The delivery system is a Rapid exchange Rx System
It is expected that ABLUMINUS sirolimus eluting stent system will significantly reduce delay in healing and thrombosis events while providing comparable results regarding restenosis to other DES systems on the market
12 Therapeutic Agent-Sirolimus Drug
Sirolimus is a cytostatic drug used for treatment of various disease in Humans The drug works on FKBP-12 protein and inhibits growth factor-simulated cell proliferation Sirolimus forms a complex with FKBP Protein that inhibits the cell cycle between G0 and G1 phase This results in interruption of the cascade governing cell growth metabolism and proliferation
13 STENT PLATFORM ABLUMINUS sirolimus eluting stent system is a combination product comprised of two key components the Stent which includes the active pharmaceutical ingredient API Sirolimus drug incorporated into a bio-degradable polymer coating and delivery catheter A balloon expandable L605 chromium cobalt stent with bio-degradable polymer coating containing Sirolimus drug is pre-mounted onto a highly deliverable semi-compliant rapid exchange delivery system The delivery catheter has two radiopaque markers which mark the ends of the stent to facilitate proper positioning and placement The catheter has hydrophilic coating facilitating easy delivery of the system
The Stent has a biodegradable polymer matrix consisting of Poly L Lactic acid PLLA which has been wide spread application in medical devices The Poly lactic acid its co-polymers and mixtures have been evaluated in pre-clinical studies and clinical studies around the world revealing favourable bio-compatibility profile The bio-degradable polymer has been demonstrated to be safe when used as an implant or drug release-control polymer for both animal and humans
2 RISK ANALYSIS
As with any patient undergoing percutaneous coronary intervention subject in this registry may experience adverse events andor outcomes that may include but are not necessarily limited to the following
Abrupt stent closure or failure to expand the stent
Abrupt vessel closure or spasm
Acute myocardial infarction
Allergic reaction to anti-coagulation andor anti thrombotic therapy contrast material or stent andor delivery system materials
Aneurysm pseudo aneurysm or arteriovenous fistula
Arrhythmias including ventricular fibrillation and ventricular tachycardia
Cardiac tamponade
Cardiogenic shock
Death
Dissection perforation or rupture of the coronary artery
Emboli distal air tissue or thrombic emboli
Emergency coronary artery bypass graft CABG as a result of damage to the stent injury to the vessel
Fever
Hematoma at insertion site
Haemorrhage requiring transfusion
Hypotensionhypertension
Infection andor pain at site of insertion
Late stent thrombosis stent thrombosis occlusion
Perforation or rupture of artery
Peripheral ischemia or peripheral nerve injury
Stroke or transient ischemia attack
Renal failure
Restenosis of stented segment
Stent migration or stent embolization
Total occlusion of coronary artery
Unstable angina
Adverse events that may be associated with Sirolimus drug coating
Allergicimmunologic reaction to drug or stent coating
Alopecia
Anaemia
Blood product transfusion
Gastrointestinal symptoms
Haematologicaldyscrasia including leukopenia neutropenia thrombocytopenia
Hepatic enzyme changes
Histological changes in vessel wall including inflammation cellular damage or necrosis
MyalgiaArthralgia
Peripheral neuropathy
Appropriate contraindications and warnings are also included in the instructions for use provided with the device Interventional cardiologists are invited to participate as investigators in this registry All clinicians will have experience with the treatment and control procedures and have been trained on the use implantation of a Drug Eluting stent system
3 AIM OF THE REGISTRY
The purpose of this registry is to capture clinical data of ABLUMINUS sirolimus eluting stent in real world all comer patients with Diabetes Mellitus
4 REGISTRY DESIGN
Prospective Observational Multi-center clinical registry to be conducted in Italy at 15 Interventional cardiology centers 1000 patients will be enrolled and evaluated All the patients will be followed up for up to 5 years
41 Treatment Strategy
The investigator will determine the treatment strategy It is recommended that each enrolling investigator review the most recent IFU to assess contraindications warnings and precautions for treating potential patients
5 ENDPOINT
51 Primary endpoints
Target Lesion Failure which is composite of cardiac death target-vessel myocardial infarction and clinically indicated target lesion revascularisation within 12 months
Components of the primary end point are defined as follows
Cardiac Death any death due to immediate cardiac cause deaths related to the procedure unwitnessed death and death of unknown cause
Target Vessel Myocardial infarction categorized according to the Minnesota electrocardiographic criteria Q-wave and non-Q-wave Spontaneous myocardial infarction was defined as a typical rise and fall of creatinine kinase-MB fraction or troponin in the presence of at least one of several conditions ischemic symptoms new pathological Q waves ischemic electrocardiographic changes or pathological evidence of acute myocardial infarction Peri-procedural myocardial infarction was defined as an increase in creatinine kinase to more than twice the normal value with increased values of confirmatory biomarkers creatinine kinase-MB fraction or troponin higher than usual Target-vessel-related myocardial infarction was one related to the target vessel or that could not be clearly related to another vessel
Clinically indicated target lesion revascularisation any repeat percutaneous or surgical intervention due to a stenosis or occlusion within the device of the index procedure 52 Secondary endpoints
Stent thrombosis Time Frame 1 month 12 months yearly Definite and probable stent thrombosis according to ARC definitions
Cardiac death Time Frame 1 month 12 months yearly
Target Vessel Myocardial infarction Time Frame 1 month 12 months yearly
Target Lesion Revascularisation Time Frame 1 month 12 months yearly
Device Success at 24 hours
Lesion Success at 24 hours
Procedural Success at 24 hours
6 REGISTRY POPULATION
61 Number of patients 1000 patients will be enrolled at 15 interventional cardiology sites in Italy Duration of enrollment will be 12 months
62 Type of Patient Patients eligible for PCI Percutaneous Coronary Intervention with lesions suitable for stent implantation and having diabetes Mellitus will be included according to the inclusion and exclusion criteria specified below The inclusion criteria will be kept comprehensive to reflect routine clinical practice of treatment Real world Scenario-All comer patients
1 Inclusion Criteria
1 The patient must be at least 18 years of age 2 Diabetic patient having clinical evidence of myocardial ischemia eg stable or unstable angina silent ischemia or positive functional study acute coronary syndromes will be considered
3 The patient is an acceptable candidate for percutaneous trans luminal coronary angioplasty PTCAstenting and emergent coronary artery bypass graft CABG surgery
4 Culprit de novo lesion in a native coronary artery with significant stenosis 50 by visual estimate eligible for stent implantation no limitation on the number of treated lesions vessel and lesion length 5 Patients included are those for whom the physician has already considered worthwhile the use of Abluminus Stent according to the indications provided by the IFU 6 Patient provides written informed consent 7 Patient agrees to all required follow-up procedures and visits
2 Exclusion Criteria
1 The patient has a known hypersensitivity or contraindication to any of the following medications Heparin Aspirin Both Clopidogrel and Ticlopidine Sirolimus Paclitaxel ABT 578 Stainless steel Chromium Cobalt biodegradable PLLA polymer
2 Patients with hypersensitivity to contrast media who cannot be treated with adequate prophylaxis
3 Female of childbearing potential unless a recent pregnancy test is negative who possibly plan to become pregnant any time after enrollment into this study
4 History of bleeding diathesis or known coagulopathy including heparin-induced thrombocytopenia or will refuse blood transfusions
5 Patients who are actively participating in another drug or device investigational study which have not completed the primary endpoint follow-up period
6 Previous coronary intervention on target vessel
7 Non-cardiac co-morbid conditions are present with life expectancy 1 year or that may result in protocol non-compliance per site investigators medical judgment
8 Lesions not allowing a complete balloon inflation or stent deployment
7 REGISTRY PROCEDURES
71 Patient Information
Eligible patients will be informed about the registry and have to sign informed consent before or after the procedure see Appendix I informed consent form
72 Baseline Evaluation
At inclusion into registry the following routine examination if performed will be captured
1 Physical examination and relevant medical history 2 Angina status 3 Routine laboratory tests including complete blood count CBC blood chemistry blood sugar and lipids CK andor CK-MB prior to the procedure In case of acute myocardial infarction or infarct extension we suggest CK andor CK-MB immediately prior to the procedure and serial measurements every 8 hours after the procedure until the peak CK level has been defined 4 12-lead electrocardiogram before the procedure
73 Stent Implantation
During the index procedure only ABLUMINUS sirolimus eluting stent system will be implanted Using the instruction for use IFU provided with the device the investigator will choose the appropriate length and diameter of the stents to be implanted by visual estimation
The choice of the length of the stent should ensure complete coverage of the lesion If more than one stent is implanted at least 2 mm overlap should be achieved In case of insufficient stent expansion the stent will be post-dilated with an appropriately sized balloon
Treatment of multiple target vessels within the same procedure and staged procedures which occur within 90 days of the initial implant procedure are allowed ABLUMINUS sirolimus eluting stent system implanted in non-target vessels after 90 days after the initial implant procedure will not be followed under the ABLUMINUS sirolimus eluting stent system registry protocol
As such any subsequent treatment of the lesion already present at the time of baseline procedure will be considered as a staged procedure instead of a repeat PCI In the CRF Case Report Form the investigator will complete a staged procedure module indicating that this lesion was present at the time of first procedure The lesions diagnosed and treated at the later stages will not be considered as repeat revascularization
For each individual lesion treated a separate lesion form in the CRF needs to be completed Every vessel in which anABLUMINUS sirolimus eluting stent system is implanted or in which an attempt to implant anABLUMINUS sirolimus eluting stent system is made within 90 days of the initial implant procedure is considered a target vessel
For patient undergoing a staged procedure the follow up schedule will be calculated from the date of initial ABLUMINUS sirolimus eluting stent system implant procedure
8 ANTITHROMBOTIC TREATMENT
Pre- procedure Aspirin 75mg minimum
Patients without any therapy clopidogrel bisulphate loading dose of 300-600mg per os before or during the procedure
Patient on clopidogrel therapy within 7 days prior no loading dose required
Ticagrelor or Prasugrel in the case of Acute Coronary Syndromes
During Procedure At least 5000IE or 70-100IEKg unfractioned heparin to maintain an ACT 250 seconds during the procedure
Post-procedure DAPT Therapy for at least 6 months IFU or longer according to current Guidelines Aspirin 75mg per os life long
Or according to standard clinical practice The use of GP IIB IIIA inhibitors is left to the discretion of the operator
9 FOLLOW-UP PERIOD
Patients will be followed after hospital discharge up to 5 years after the index procedure This includes telephone contacts to obtain information regarding medical history cardiovascular drug use hospitalizations and adverse events at 1 month 6 months 12 months and then yearly post procedure Apart from clinical follow -ups there is angiographic follow-up which is clinically driven symptom driven
10 SERIOUS ADVERSE EVENT REPORTING
101 Serious Adverse Events SAEs
An adverse event AE is report as serious which lead to
Death
Life-threatening illness or injury or
Permanent impairment of a body structure or a body function or
In-patient or prolonged hospitalization see note below or
Medical or surgical intervention to prevent life-threatening illness or injury or permanent impairment to a body structure or a body function
Note For the purposes of this study in-patient hospitalization is defined as the subject being admitted to the hospital with the exception of any planned hospitalization for a pre-existing condition or a procedure required by the local standard of care which do not have to be reported as an SAE
All serious adverse events must be reported to the Principal Investigator within 24 hours of discovery or notification of the event and to the local EC as per local requirements
The Principal Investigator is responsible for reporting adequate information on SAEs that may be related to the study device to the regulatory authorities per countrys applicable reporting requirements
102 Unanticipated Serious Adverse Device Effect USADE
Any serious adverse effect on the health or safety or any life-threatening problem or death caused by or associated with a device if that effect problem or death was not previously identified in nature severity or degree of incidence in the investigational plan or application including a supplementary plan or application or any other unanticipated serious problem associated with a device that relates to the rights safety or welfare of subjects
Unanticipated Adverse Device Effects must be reported to the manufacturer as soon as possible following the standard vigilance route Reporting the event ONLY in the CRF is not an option
11 MACE ADJUDICATION
All registry devices related Major Adverse Cardiac Events MACE will be reviewed classified by the treating physician In case of a stent thrombosis or severe stent restenosis these events will verify the stent thrombosis determine the Diameter Stenosis DS by QCA
12 STATISTICAL ANALYSIS
121 Analysis Population All patients who are successfully registered will be included in the analysis
122 Sample Size Calculations and Assumptions Being this an observational registry aiming at quantifying effect estimates without direct comparisons to literature benchmarks we proceeded without a formal power analysis As the main analysis is a pooled analysis of all included patients an overall and comprehensive analysis is planned as the primary analytical approach to reflect real-world patients and practice
123 Statistical Analyses Continuous endpoints will be summarized by presenting the total number of patients mean standard deviation median minimum and maximum Tabulation of categorical parameters will include counts and percentages Survival analysis will be performed with the Kaplan-Meier method Statistical inference will be based on the computation of 95 confidence intervals using the adjusted Wald method Additional analyses will involve key subgroups defined according to baseline and procedural features with statistical significance set at the 5 2-tailed level Specifically Student t Fisher exact and log-rank tests will be used for such bivariate analyses whereas multivariable linear regression logistic regression and Cox proportional hazard analyses will be used to adjust for confounders
13 QUALITY CONTROL AND ASSURANCE
131 Quality Assurance The Principal Investigator of the Centre is responsible for the overall clinical management of patients admitted to his center and assumes global responsibilities for him and his staff and the data obtained from study participants he ensures compliance with the protocol laws and regulations ensures informed consent to be signed and that the CRF is accurate and complete
In accordance with Italian law and the ICHGCP guidelines the investigators and the institution will allow representatives of regulatory agencies and Ethics Committee direct access for review of the original documentation of patients to verify compliance with the procedures and the veracity of the data
132 Source Data The investigator assures that medical files are appropriately stored and completed Each follow up contact will be reported in the source data should at least contain the information collected by the registry The investigator assures that medical files and case record forms are accessible for inspection by Competent Authorities
133 Monitoring The study will be performed according to good clinical practice The collection of personal procedural and clinical data of patients must take place into the electronic CRF to which will only have access the individual investigators and the study principal investigator Dr Luca Testa as administrator
134 Publication policy All study investigators are committed to publishing the results at both conferences and international journals The PI of the study will have the right to present the main results before other investigators and will be the owner of the data After obtaining the consent of the PI the other experimenters will publish and present the full or partial results of the study
All investigators undertake to publish the study results whether they are positive negative or unexpected
14 ETHICAL CONSIDERATION
141 General Guidelines This registry will be conducted in accordance with ICH- GCP Good Clinical Practices The registry will be performed in accordance with the Declaration of Helsinki and ISO 141552011 and MED DEV 271 rev 3
142 Ethics Committee The protocol informed consent form and other registry-related documents will be submitted to the Institutional or Local Ethics Committee if applicable or are required for approval to initiate
143 Informed Consent A signed Informed Consent sample attached must be obtained before enrolment Importantly patients participation in the study is voluntary thus they may decide to terminate their involvement at any time by withdrawing consent
Bibliography
1 Stefanini GG Holmes DR Jr Drug-eluting coronary-artery stents N Engl J Med 2013368254-65
2 Serruys PW HE Luijten KJ Beatt et al Incidence of restenosis after successful coronary angioplasty a time-related phenomenon A quantitative angiographic study in 342 consecutive patients at 1 2 3 and 4 months Circulation 1988772361-371
3 Fihn SD Blankenship JC Alexander KP et al 2014 ACCAHAAATSPCNASCAISTS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease a report of the American College of CardiologyAmerican Heart Association Task Force on Practice Guidelines and the American Association for Thoracic Surgery Preventive Cardiovascular Nurses Association Society for Cardiovascular Angiography and Interventions and Society of Thoracic Surgeons J Am Coll Cardiol 2014 641929-49
4 Windecker S Kolh P Alfonso F et al 2014 ESCEACTS Guidelines on myocardial revascularization The Task Force on Myocardial Revascularization of the European Society of Cardiology ESC and the European Association for Cardio-Thoracic Surgery EACTS developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions EAPCI Eur Heart J 2014 352541-619
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None