Ignite Creation Date:
2024-05-05 @ 5:20 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00435266
Status:
COMPLETED
Last Update Posted:
2009-02-17
First Post:
2007-02-13
Brief Title:
Remote Ischemic Preconditioning in Primary PCI
Sponsor:
University of Aarhus
Organization:
University of Aarhus
Study Overview
Official Title:
The Effect of Remote Preconditioning in Primary Percutaneous Intervention of Acute ST Elevation Myocardial Infarction
Status:
COMPLETED
Status Verified Date:
2009-02
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:
None
Brief Summary:
Primary percutaneous coronary intervention pPCI is the preferred treatment in ST elevation myocardial infarction STEMI The infarct-related artery IRA can be opened in more than 90 of the patients However STEMI patients still end up with a persistent perfusion defect of highly variable magnitude indicating that adjunctive treatment may add further protection against tissue damage Ischemic preconditioning IPC is an intervention by which myocardium threatened by ischemia is exposed to short and repeated sublethal ischemic episodes prior to sustained ischemia local IPC A systemic response with protection of more remote organs remote IPC rIPC also can be induced We have recently found that the infarct reducing effect can be obtained by obstruction of an extremity even though the remote stimulus is initiated during sustained occlusion of a coronary artery the so-called remote preconditioning rPerC The clinical perspective is now to examine if rPerC can reduce the infarct size in patients with unpredictable ischemia in ST elevation myocardial infarction STEMI We perform a randomized study where patients en route for pPCI are allocated to either rPerC or a standard treatment to evaluate whether the tissue damage can be reduced Effect measure will be infarct size determined by scintigraphy final infarct size and salvage
Detailed Description:
Primary percutaneous coronary intervention pPCI is the preferred treatment in ST elevation myocardial infarction STEMI The infarct-related artery IRA can be opened in more than 90 of the patients However STEMI patients still end up with a persistent perfusion defect of highly variable magnitude indicating that adjunctive treatment may add further protection against tissue damage Ischemic preconditioning IPC is an intervention by which myocardium threatened by ischemia is exposed to short and repeated sublethal ischemic episodes prior to sustained ischemia local IPC A systemic response with protection of more remote organs remote IPC rIPC also can be induced We have recently found that the infarct reducing effect can be obtained by obstruction of an extremity even though the remote stimulus is initiated after sustained occlusion of a coronary artery the so-called remote preconditioning rPerC The clinical perspective is now to examine if rPerC can reduce the infarct size in patients with unpredictable ischemia in ST elevation myocardial infarction STEMI We perform a randomized study where patients en route for pPCI are allocated to either rPerC or a standard treatment to evaluate whether the tissue damage can be reduced Effect measure will be infarct size determined by scintigraphy final infarct size and salvage
Purpose
The purpose of the present study is to examine the utility of rPerC in STEMI patients treated with pPCI The effect will be evaluated by 1 limitation of infarct size salvage and final infarct size determined by myocardial scintigraphy SPECT 2 electrocardiographic and angiographic signs of tissue perfusion 3 release of ischemic markers 5 echocardiographic markers of left ventricular function and 5 clinical end-points Major Adverse Cardiac Events MACE death reinfarction need for revascularisation invalidating stroke at discharge and after 30 days
Description and evaluation of the ethical aspects of the study
Study patients treated with pPCI are randomized to pretreatment with rPerC or no pretreatment control group The randomization will take place in the ambulance or at the local hospital With the aim of not causing unnecessary delays the pretreatment is discontinued if the patient arrives at the cath lab before the pretreatment is completedThe discomfort in connection with the pretreatment has been shown to be minimal
Information regarding study population
The patients are recruited among patients admitted or transferred to Department of Cardiology B Skejby Sygehus for pPCI treatment for STEMI
Review on the methods used
rPerC The pretreatment in the rPerC group comprises 4 x 5 min occlusion of right upper extremity followed by 5 min reperfusion which is performed during the transportation towards Skejby Sygehus The occlusion is obtained by inflation of a blood pressure tourniquet placed on the patients right thigh to 200 mm Hg or 25 mmHg above the patients systolic blood pressure when higher than 200 mm Hg
Angiography The initial angiography is performed in at least two planes after administration of nitroglycerin 02 mg intracoronary and filmed at 25 framessec The lesion should be placed centrally in the picture with the tip of the guiding catheter visual in the picture
The final angiography is performed in the same planes as the initial angiography and after administration of nitroglycerin 02 mg intracoronary The angiography is filmed at 25 framessec and the filming is continued until a clear projection of sinus coronarius The angiogram is filmed with and without magnification with the aim of projecting the periphery of the vessels
The final angiography is performed two minutes after the last dilatation - provided that the patient is hemodynamically stable
Percutaneous intervention and antithrombotic treatment The patients will have PCI performed in accordance with the existing procedures and guidelines at Skejby Hospital
Electrocardiogram ECG and monitoring Continuous 12-lead ST-monitoring is initiated on scene by use of a commercial monitor-defibrillator LIFEPAK 12 Medtronic Emergency Response Systems USA and continued during transport to the local hospital if not bypassed and during transfer to the interventional hospital On arrival at the interventional hospital traditional ECG electrodes are replaced by radiolucent carbon fiber lead wire electrodes Ambu Blue Sensor QR electrodes Ambu AS Denmark enabling ST-monitoring to be continued during and 90 minutes following PCI The analog ECG signals sampled by the system are digitized at a sample rate of 500 Hz for processing by the GEMarquette Medical Systems 12SL ECG interpretive algorithm At 30-second interval the ST-monitoring program generates a median QRST-complex for all 12 leads based on a 10-second epoch of ECG data From each of these median QRST-complexes the program estimates the ST-deviation at the STM point halfway between the J-point of the QRS complex and the start of the T-wave If a 01 mV change in ST-deviation lasts for 25 minutes then the software automatically acquires and stores a 10-second 12-lead ECG waveform All 12-lead ECG waveforms and continuous ST-monitoring data are transferred to a personal computer and stored by a random key for subsequent blinded analysis at the Core Lab at Skejby Sygehus
Biochemical ischemia markers Circulating concentrations of troponin T TnT is measured at arrival 8-12 hours 20-24 hours and finally 90-102 hours after symptom onset
Scintigraphic methods Two scintigraphic examinations are performed to determination of area at risk AAR final infarct size FIS regional wall motion and regional wall thickening respectively
Area at risk AAR That part of left ventricle that is without perfusion prior to PCI Determined by tracer injection during ongoing coronary occlusion which means tracer injection prior to PCI but imaging after pPCI
Final infarct size FIS That part of left ventricle that is without perfusion 1 month after PCI Determined by myocardial scintigraphy at rest 1 month after pPCI
The following parameters are calculated
Salvage AAR minus FIS of left ventricle Salvage index Salvage AAR Left ventricular ejection fraction LVEF EDV - ESVEDV Each myocardial scintigraphy is performed after administration of 700 10 MBq 99mTc-Sestamibi as an intravenous bolus injection Acquisition is performed as gated SPECT within 8 hours after tracer injection The myocardial perfusion is analyzed and quantitized by the use of the interpretation software QPS and QGS At each examination partly myocardial perfusion defect as a percentage of left ventricular myocardium partly left ventricular end-diastolic and end-systolic volume EDV and ESV and partly regional wall motion and wall thickening is determined
Design and data registration The patients are randomized to pPCI treatment with or without prior rIPC All data analyzes from the study will be analyzed blinded regarding to the patients randomization
For each participant included in the study a case record form CRF is filled in
Definition and characteristic of effect parameters and other registered data A consecutive patient registration is performed by a characteristic of the study population and a registration of causes of exclusion Clinical angiographic and procedure related variables as in the West-Danish Heart Database will be used
Data evaluation For each of the primary and secondary clinical effect parameters a comparative examination of the rPerC and not rPerC treated patient groups is performed
Statistics Dimensioning the study Previous investigations have shown that area at risk in connection with STEMI is approximately 30 of left ventricle Experiences from investigations at Department of Cardiology B and Department of Nuclear Medicine Skejby Sygehus have shown that the final infarct size in STEMI patients treated with pPCI is approximately 15
It is estimated that a 20 reduction in infarct size eg from 15 to 12 will be clinically relevant With a spreading of the infarct size of 15 which are in accordance with our previous findings detection of such a reduction with a risk of type 2 errors of 80 2α080 will require 109 patients in each group We plan inclusion of a total of 250 patients to secure complete data
The study will be analyzed after intention-to-treat principles A final specification will be performed with unpaired parametric or non parametric statistics
Purpose
The purpose of the present study is to examine the utility of rPerC in STEMI patients treated with pPCI The effect will be evaluated by 1 limitation of infarct size salvage and final infarct size determined by myocardial scintigraphy SPECT 2 electrocardiographic and angiographic signs of tissue perfusion 3 release of ischemic markers 5 echocardiographic markers of left ventricular function and 5 clinical end-points Major Adverse Cardiac Events MACE death reinfarction need for revascularisation invalidating stroke at discharge and after 30 days
Description and evaluation of the ethical aspects of the study
Study patients treated with pPCI are randomized to pretreatment with rPerC or no pretreatment control group The randomization will take place in the ambulance or at the local hospital With the aim of not causing unnecessary delays the pretreatment is discontinued if the patient arrives at the cath lab before the pretreatment is completedThe discomfort in connection with the pretreatment has been shown to be minimal
Information regarding study population
The patients are recruited among patients admitted or transferred to Department of Cardiology B Skejby Sygehus for pPCI treatment for STEMI
Review on the methods used
rPerC The pretreatment in the rPerC group comprises 4 x 5 min occlusion of right upper extremity followed by 5 min reperfusion which is performed during the transportation towards Skejby Sygehus The occlusion is obtained by inflation of a blood pressure tourniquet placed on the patients right thigh to 200 mm Hg or 25 mmHg above the patients systolic blood pressure when higher than 200 mm Hg
Angiography The initial angiography is performed in at least two planes after administration of nitroglycerin 02 mg intracoronary and filmed at 25 framessec The lesion should be placed centrally in the picture with the tip of the guiding catheter visual in the picture
The final angiography is performed in the same planes as the initial angiography and after administration of nitroglycerin 02 mg intracoronary The angiography is filmed at 25 framessec and the filming is continued until a clear projection of sinus coronarius The angiogram is filmed with and without magnification with the aim of projecting the periphery of the vessels
The final angiography is performed two minutes after the last dilatation - provided that the patient is hemodynamically stable
Percutaneous intervention and antithrombotic treatment The patients will have PCI performed in accordance with the existing procedures and guidelines at Skejby Hospital
Electrocardiogram ECG and monitoring Continuous 12-lead ST-monitoring is initiated on scene by use of a commercial monitor-defibrillator LIFEPAK 12 Medtronic Emergency Response Systems USA and continued during transport to the local hospital if not bypassed and during transfer to the interventional hospital On arrival at the interventional hospital traditional ECG electrodes are replaced by radiolucent carbon fiber lead wire electrodes Ambu Blue Sensor QR electrodes Ambu AS Denmark enabling ST-monitoring to be continued during and 90 minutes following PCI The analog ECG signals sampled by the system are digitized at a sample rate of 500 Hz for processing by the GEMarquette Medical Systems 12SL ECG interpretive algorithm At 30-second interval the ST-monitoring program generates a median QRST-complex for all 12 leads based on a 10-second epoch of ECG data From each of these median QRST-complexes the program estimates the ST-deviation at the STM point halfway between the J-point of the QRS complex and the start of the T-wave If a 01 mV change in ST-deviation lasts for 25 minutes then the software automatically acquires and stores a 10-second 12-lead ECG waveform All 12-lead ECG waveforms and continuous ST-monitoring data are transferred to a personal computer and stored by a random key for subsequent blinded analysis at the Core Lab at Skejby Sygehus
Biochemical ischemia markers Circulating concentrations of troponin T TnT is measured at arrival 8-12 hours 20-24 hours and finally 90-102 hours after symptom onset
Scintigraphic methods Two scintigraphic examinations are performed to determination of area at risk AAR final infarct size FIS regional wall motion and regional wall thickening respectively
Area at risk AAR That part of left ventricle that is without perfusion prior to PCI Determined by tracer injection during ongoing coronary occlusion which means tracer injection prior to PCI but imaging after pPCI
Final infarct size FIS That part of left ventricle that is without perfusion 1 month after PCI Determined by myocardial scintigraphy at rest 1 month after pPCI
The following parameters are calculated
Salvage AAR minus FIS of left ventricle Salvage index Salvage AAR Left ventricular ejection fraction LVEF EDV - ESVEDV Each myocardial scintigraphy is performed after administration of 700 10 MBq 99mTc-Sestamibi as an intravenous bolus injection Acquisition is performed as gated SPECT within 8 hours after tracer injection The myocardial perfusion is analyzed and quantitized by the use of the interpretation software QPS and QGS At each examination partly myocardial perfusion defect as a percentage of left ventricular myocardium partly left ventricular end-diastolic and end-systolic volume EDV and ESV and partly regional wall motion and wall thickening is determined
Design and data registration The patients are randomized to pPCI treatment with or without prior rIPC All data analyzes from the study will be analyzed blinded regarding to the patients randomization
For each participant included in the study a case record form CRF is filled in
Definition and characteristic of effect parameters and other registered data A consecutive patient registration is performed by a characteristic of the study population and a registration of causes of exclusion Clinical angiographic and procedure related variables as in the West-Danish Heart Database will be used
Data evaluation For each of the primary and secondary clinical effect parameters a comparative examination of the rPerC and not rPerC treated patient groups is performed
Statistics Dimensioning the study Previous investigations have shown that area at risk in connection with STEMI is approximately 30 of left ventricle Experiences from investigations at Department of Cardiology B and Department of Nuclear Medicine Skejby Sygehus have shown that the final infarct size in STEMI patients treated with pPCI is approximately 15
It is estimated that a 20 reduction in infarct size eg from 15 to 12 will be clinically relevant With a spreading of the infarct size of 15 which are in accordance with our previous findings detection of such a reduction with a risk of type 2 errors of 80 2α080 will require 109 patients in each group We plan inclusion of a total of 250 patients to secure complete data
The study will be analyzed after intention-to-treat principles A final specification will be performed with unpaired parametric or non parametric statistics
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None