Ignite Creation Date:
2024-05-06 @ 11:54 AM
Last Modification Date:
2024-10-26 @ 12:51 PM
Study NCT ID:
NCT03621501
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2022-11-08
First Post:
2018-02-08
Brief Title:
Direct Complete Versus Staged Complete Revascularization in Patients Presenting With Acute Coronary Syndromes and Multivessel Disease
Sponsor:
Erasmus Medical Center
Organization:
Erasmus Medical Center
Study Overview
Official Title:
Percutaneous Complete Revascularization Strategies Using Sirolimus Eluting Biodegradable Polymer Coated Stents in Patients Presenting With Acute Coronary Syndrome and Multivessel Disease
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2022-11
Last Known Status:
None
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:
BioVasc
Brief Summary:
To test whether immediate complete revascularization is non-inferior to staged but within six weeks after index procedure complete revascularization in Patients presenting with ACS including Non-ST-elevation ACS NSTEACS and ST-elevation myocardial infarction STEMI with multivessel disease accepted for PCI
Detailed Description:
Invasive coronary angiography followed by percutaneous coronary intervention is the treatment of choice in patient presenting with STEMI-ACS1 and NSTE-ACS2 Up to 60 percent of these patients have multivessel disease on angiography3-5 Patients with multivessel disease have a worse prognosis compared with patients having culprit vessel disease only5 It has been debated whether a complete or culprit artery only revascularization strategy is better
Retrospective data in STEMI patients suggested a lower mortality in patients that were treated with culprit artery only compared with multivessel PCI during index procedure6 Since then four randomized controlled trials have addressed this question in STEMI population The Randomized Trial of Preventive Angioplasty in Acute Myocardial Infarction PRAMI trial n 465 23 months follow-up7 the Randomized trial of complete versus lesion-only revascularization in patients undergoing primary percutaneous coronary intervention for STEMI and multivessel disease CvLPRIT n 296 12months follow-up8 the Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease DANAMI-3-PRIMULTI trial n 627 27months follow-up9 and the Fractional Flow Reserve-Guided Multivessel Angioplasty in Myocardial Infarction Compare-Acute trial n 885 12 months follow-up10 PCI of the non-infarct related artery was performed at the index procedure PRAMI and Compare-Acute staged before discharge DANAMI-3-PRIMULTI or at any time during hospitalization CvLPRIT Indication for PCI was significant stenosis as assessed by angiography PRAMI and CvLPRIT or FFR DANAMI-3-PRIMULTI and COMPARE-ACUTE There was a significant reduction in primary outcome in all four trials in favor of complete revascularization However there was no significant reduction in total mortality or myocardial infarction Based on the results for these four trials the 2017 ESC STEMI-ACS guidelines gave a class II level of evidence LOE A indication for routine complete revascularization in STEMI patients with multivessel disease including those presenting with cardiogenic shock1 However an important shortcoming of the abovementioned studies is the absence of a staged complete revascularization arm As there is no data that compare immediate and staged complete revascularization the guidelines dont advise on when to perform non-infarct related artery revascularization
Data regarding optimal treatment in NSTEMI-ACS are more scarce In an observational study by Shishesbor and coworkers they showed that nonculprit multivessel stenting reduced future revascularization rate but this was not associated with lower rate of death or myocardial infarction11 Recently a substudy from the Bleeding complications in a Multicenter registry of patients discharged with diagnosis of acute coronary syndrome BleeMACS registry N4520 patients 1459 NSTEMI was published12 They showed that in NSTEMI patients complete revascularization was associated with a significant lower rate of death 45 vs 85 p0002 re-AMI 37 vs 66 p0016 and MACE 81 vs 139 p0001 at one year follow up The 2015 ESC NSTEMI-ACS guidelines not specifically advise a culprit only or multivessel PCI strategy Moreover they advise to base revascularization strategy on patients clinical status and co-morbidities as well as disease severity Class II LEO B Interestingly in contrast with the STEMI population in NSTEMI population there is a small RCT investigating staged versus direct complete revascularization the Single-Staged Compared With Multi-Staged PCI in Multivessel NSTEMI Patients The SMILE Trial N584 patients13 There was a significant reduction in primary endpoint 1S-PCI n 36 1363 vs MS-PCI n 61 2319 hazard ratio HR 0549 95 confidence interval CI 0363 to 0828 p 0004 at one year follow up This was mainly driven by a reduction in target vessel revascularization There was no significant difference in cardiac death or myocardial infarction between the both groups This finding deserves further investigation because the TVR rate 154 at 1 year in the multistage group was unprecedentedly high in the era of current-generation drug-eluting stents
There is no publication specifically addressing the patients with unstable angina regarding the subject of complete or incomplete revascularization or timing of revascularization
Considering such data complete revascularization in ACS patients seems advisable but timing of revascularization is unknown
Given this background no investigation so far provided a comprehensive evaluation of the complete revascularization strategies for patients with any type of acute coronary syndrome and multivessel disease Therefore the investigators aim to investigate in a randomized controlled trial the commonly used complete revascularization strategies for patients presenting with ACS 1 Immediate complete revascularization 2 Culprit only plus staged complete revascularization within six weeks after index procedure in terms of the primary endpoint the composite of death from any cause nonfatal type 1 myocardial infarction revascularization and cerebrovascular events at 1-year post intervention
Patients will be treated with one commercially available second-generation drug-eluting stent stent to ensure homogeneity of treatment among patients abolishing the occurrence of bias due to different stent usage The stents used will be the Biotronik Orsiro DES Sirolimus-Eluting stent The Orsiro DES is a second generation DES with a bioabsorbable polymer coating releasing sirolimus and was CE marketed in 2011 The bioabsorbable nature of the polymer could be associated with a reduction of the inflammatory response reducing neo-intima growth compared to a durable polymer14 15 The active drug sirolimus is a lipophilic molecule that inhibits mammalian target of rapamycine mTOR on smooth muscle cells also preventing neo-intima hyperplasia16 The Orsiro stent has ultrathin cobalt chromium struts of 60-80micron depending on stent size enhancing deliverability and crossability without loss of radial strength or fatigue resistance The Orsiro stent has been extensively studied in different study populations with more than 32500 patients studied globally
Retrospective data in STEMI patients suggested a lower mortality in patients that were treated with culprit artery only compared with multivessel PCI during index procedure6 Since then four randomized controlled trials have addressed this question in STEMI population The Randomized Trial of Preventive Angioplasty in Acute Myocardial Infarction PRAMI trial n 465 23 months follow-up7 the Randomized trial of complete versus lesion-only revascularization in patients undergoing primary percutaneous coronary intervention for STEMI and multivessel disease CvLPRIT n 296 12months follow-up8 the Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease DANAMI-3-PRIMULTI trial n 627 27months follow-up9 and the Fractional Flow Reserve-Guided Multivessel Angioplasty in Myocardial Infarction Compare-Acute trial n 885 12 months follow-up10 PCI of the non-infarct related artery was performed at the index procedure PRAMI and Compare-Acute staged before discharge DANAMI-3-PRIMULTI or at any time during hospitalization CvLPRIT Indication for PCI was significant stenosis as assessed by angiography PRAMI and CvLPRIT or FFR DANAMI-3-PRIMULTI and COMPARE-ACUTE There was a significant reduction in primary outcome in all four trials in favor of complete revascularization However there was no significant reduction in total mortality or myocardial infarction Based on the results for these four trials the 2017 ESC STEMI-ACS guidelines gave a class II level of evidence LOE A indication for routine complete revascularization in STEMI patients with multivessel disease including those presenting with cardiogenic shock1 However an important shortcoming of the abovementioned studies is the absence of a staged complete revascularization arm As there is no data that compare immediate and staged complete revascularization the guidelines dont advise on when to perform non-infarct related artery revascularization
Data regarding optimal treatment in NSTEMI-ACS are more scarce In an observational study by Shishesbor and coworkers they showed that nonculprit multivessel stenting reduced future revascularization rate but this was not associated with lower rate of death or myocardial infarction11 Recently a substudy from the Bleeding complications in a Multicenter registry of patients discharged with diagnosis of acute coronary syndrome BleeMACS registry N4520 patients 1459 NSTEMI was published12 They showed that in NSTEMI patients complete revascularization was associated with a significant lower rate of death 45 vs 85 p0002 re-AMI 37 vs 66 p0016 and MACE 81 vs 139 p0001 at one year follow up The 2015 ESC NSTEMI-ACS guidelines not specifically advise a culprit only or multivessel PCI strategy Moreover they advise to base revascularization strategy on patients clinical status and co-morbidities as well as disease severity Class II LEO B Interestingly in contrast with the STEMI population in NSTEMI population there is a small RCT investigating staged versus direct complete revascularization the Single-Staged Compared With Multi-Staged PCI in Multivessel NSTEMI Patients The SMILE Trial N584 patients13 There was a significant reduction in primary endpoint 1S-PCI n 36 1363 vs MS-PCI n 61 2319 hazard ratio HR 0549 95 confidence interval CI 0363 to 0828 p 0004 at one year follow up This was mainly driven by a reduction in target vessel revascularization There was no significant difference in cardiac death or myocardial infarction between the both groups This finding deserves further investigation because the TVR rate 154 at 1 year in the multistage group was unprecedentedly high in the era of current-generation drug-eluting stents
There is no publication specifically addressing the patients with unstable angina regarding the subject of complete or incomplete revascularization or timing of revascularization
Considering such data complete revascularization in ACS patients seems advisable but timing of revascularization is unknown
Given this background no investigation so far provided a comprehensive evaluation of the complete revascularization strategies for patients with any type of acute coronary syndrome and multivessel disease Therefore the investigators aim to investigate in a randomized controlled trial the commonly used complete revascularization strategies for patients presenting with ACS 1 Immediate complete revascularization 2 Culprit only plus staged complete revascularization within six weeks after index procedure in terms of the primary endpoint the composite of death from any cause nonfatal type 1 myocardial infarction revascularization and cerebrovascular events at 1-year post intervention
Patients will be treated with one commercially available second-generation drug-eluting stent stent to ensure homogeneity of treatment among patients abolishing the occurrence of bias due to different stent usage The stents used will be the Biotronik Orsiro DES Sirolimus-Eluting stent The Orsiro DES is a second generation DES with a bioabsorbable polymer coating releasing sirolimus and was CE marketed in 2011 The bioabsorbable nature of the polymer could be associated with a reduction of the inflammatory response reducing neo-intima growth compared to a durable polymer14 15 The active drug sirolimus is a lipophilic molecule that inhibits mammalian target of rapamycine mTOR on smooth muscle cells also preventing neo-intima hyperplasia16 The Orsiro stent has ultrathin cobalt chromium struts of 60-80micron depending on stent size enhancing deliverability and crossability without loss of radial strength or fatigue resistance The Orsiro stent has been extensively studied in different study populations with more than 32500 patients studied globally
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