Ignite Creation Date:
2024-05-06 @ 6:10 PM
Last Modification Date:
2024-10-26 @ 2:43 PM
Study NCT ID:
NCT05579418
Status:
NOT_YET_RECRUITING
Last Update Posted:
2022-10-13
First Post:
2022-10-10
Brief Title:
The Safety and Long-Term Clinical Benefit of PCSK9i in STEMI Patients
Sponsor:
Hamad Medical Corporation
Organization:
Hamad Medical Corporation
Study Overview
Official Title:
The Safety and Long-Term Clinical Benefit of PCSK9i in Addition to Statin Therapy in Patients With ST-Segment Elevation Myocardial Infarction A Randomized Open Label Study
Status:
NOT_YET_RECRUITING
Status Verified Date:
2022-10
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:
Patients with acute coronary syndromes ACS have an increased risk of recurrent ischemic events particularly during the first year following the index event which is mainly due to unattended risk factors and or poor compliance with medications Lowering low-density lipoprotein cholesterol LDL-C reduces cardiovascular morbidity and mortality in patients with atherosclerotic cardiovascular disease ASCVD with a magnitude of clinical benefit that is proportional to the reduction in LDL-C levels Proprotein convertase subtilisin kexin type 9 PCSK9 antibodies have emerged as a new class of drugs that rapidly and effectively lower LDL-C levels up to 77 of the original value in combination with statins
The primary objective of this study is to confirm the safety and the long-term clinical benefit associated with the use of PCSK9i when combined with statin in patients with ACS-STEMI
The study is an investigator-initiated prospective randomized open label study that will be the first study looking for the safety and the clinical benefit and outcome associated with the use of PCSK9i in ACS-STEMI patients specifically Internationally this will be the first trial studying the effect of PCSK9i on patients with acute myocardial infarction STEMI in terms of reduction in cholesterol level and reduction in cardiac events rate re-infarction and cardiac death after myocardial infarction This trial will have a significant impact in the management of patients with STEMI locally and internationally and it will be conducted purely in Qatar This trial will help to improve the clinical outcome of patients in Qatar in terms of reduction of myocardial reinfarction rate and mortality
The primary objective of this study is to confirm the safety and the long-term clinical benefit associated with the use of PCSK9i when combined with statin in patients with ACS-STEMI
The study is an investigator-initiated prospective randomized open label study that will be the first study looking for the safety and the clinical benefit and outcome associated with the use of PCSK9i in ACS-STEMI patients specifically Internationally this will be the first trial studying the effect of PCSK9i on patients with acute myocardial infarction STEMI in terms of reduction in cholesterol level and reduction in cardiac events rate re-infarction and cardiac death after myocardial infarction This trial will have a significant impact in the management of patients with STEMI locally and internationally and it will be conducted purely in Qatar This trial will help to improve the clinical outcome of patients in Qatar in terms of reduction of myocardial reinfarction rate and mortality
Detailed Description:
The study is an investigator-initiated prospective randomized open-label study Patients will be eligible for participation in the trial if they are between 18-70 years of age All patients presenting with STEMI will be screened for the trial those patients with LDL-C levels higher than guideline-recommended targets despite prior high-intensity statin therapy on statin therapy prior to hospital admission or when the LDL-C not projected to decrease below the recommended targets if they are newly initiated on high intensity statin therapy will be considered for the study
Procedures and study interventions
1 Patients hospitalized for ST-segment elevation myocardial infarction STEMI with symptom onset 12 h prior to hospitalization will be potentially eligible
2 Patient will receive the standard care as per the HH guidelines in terms of coronary angiogram standard therapy of statin dual antiplatelet B -Blockers and ACE
3 These patients will be screened for suitability to participate in the study
4 The patients will be considered for enrolment if heshe is hemodynamically stable and had a successful PPCI to De-novo lesion in an infarct related artery NOT stent thrombosis- those will be excluded from the study also acute occlusion of cardiac grafts will be excluded from the study as well
5 LDL- C will be assessed immediately post angiography The patient will be eligible for the trial if the LDL-C levels at the screening blood test is one of the following
18 mmoll if patients are on stable unchanged for 4 weeks before screening treatment with high-intensity statin
23 mmoll in patients previously taking low- or moderate-intensity statin 32 mmoll in patients not on statin treatment
6 Eligible patients will be randomly assigned in a 11 ratio to one of the two groups The control group or the intervention group
7 The control group will receive the standard guidelines directed optimal medical therapy
8 The interventional group will receive Evolocumab 140 mg every 2 weeks in addition to the standard guideline directed optimal medical therapy
9 The optimal medical therapy will include high intensity statin either atorvastatin 40-80 mgday or rosuvastatin 20-40 mg day throughout the study or maximal tolerated statin in both groups the statin dose can be titrated up or down as per the standard clinical practice
10 The study drug will be administered at baseline as early as possible but within 24 hr following hospitalization In our institute patients admitted with STEMI will receive primary percutaneous intervention by default The average time for door to balloon time is around 50 minutes department data Randomization and drug administration is not possible within such a short time in addition consider randomization and drug administration before angiography may results in delay of delivering standard therapy which is of not in the best interest of the patient
11 The randomization will be done immediately after angiography and aim for drug administration within 24 hr of admission
12 Blood samples will be obtained at baseline for assessment of fasting lipids and inflammatory markers
13 All patients recruited for the trial will receive medical treatment for ACS as per the Heart hospital and international guidelines Patients that will be considered for the trial should have received coronary angiography and revascularization percutaneous coronary intervention as per the hospital guidelines
14 Patients not fit or rejected re-vascularization with PCI or patient that will need coronary artery bypass grafting CABG surgery will be excluded from this study
15 Written informed consent will be obtained from all the patients
16 The research team may ask for supervised injection when suspect non-compliance
Information and investigation that will be collected from patient
1 Patient will have blood test Lipid panel Liver function and CRP will be done at 01 2 6 and 12 18 and 24 months
2 Carotid intimal thickening measurement at 0 6 12 24 months
3 Echocardiogram 161224 months
4 OPD Review for clinical evaluation medication side effect Chest pain hospitalization or unplanned PCI at 1236121824 months
Randomization
Participants will be randomly assigned using permuted block design with a computer random number generator the block size is fixed 8 per block with random allocation within the block to either the control group or the interventional group of the patients 4 for each group patient allocation within the block is randomly assigned Once the patient has given consent to be included in the trial heshe is then irreversibly randomized by opening the next sealed envelope within the current block containing hisher assignment
The production of computer-generated sets of random allocations will be done by a research support unit who will not be performing data collection in advance of the start of the study
Sample size calculation
Our study is designed as a superiority trial powered for the primary endpoint The average LDL-D cholesterol of patients admitted with ACS-STEMI to the Heart Hospital was 34 mmol based on calculating the average LDL-C of 150 patients with ACS-STEMI in the past 6 months department Data
Bases on the EVOPACS study above statin alone therapy will reduce the LDL-C by 35 119 mmol while Evolocumab statin combination therapy will reduce LDL-C by 77 261 mmol Expectations for cholesterol-lowering trials were set by the Cholesterol Treatment Trialists Collaborators who reported in 2005 that for each 1 mmolL 386 mgdL reduction in LDL-C cardiovascular events were reduced by a mean of 22 Based on this the expected reduction in cardiovascular event is 26 with statin therapy alone and 57 with Evolocumab statin Assuming 1000 cases of ACS-STEMI present to our emergency department every year and event rate of 17-33 post STEMI patient for those on moderate to high intensity statins at one year 90 power and 5 significance level the sample size was 144 for each arm Accounting for the nature of the country of high travel and dropout nature 20 drop rate was added to the sample size the final sample size for this trial was up rounded to 350 patients originally was 346
Procedures and study interventions
1 Patients hospitalized for ST-segment elevation myocardial infarction STEMI with symptom onset 12 h prior to hospitalization will be potentially eligible
2 Patient will receive the standard care as per the HH guidelines in terms of coronary angiogram standard therapy of statin dual antiplatelet B -Blockers and ACE
3 These patients will be screened for suitability to participate in the study
4 The patients will be considered for enrolment if heshe is hemodynamically stable and had a successful PPCI to De-novo lesion in an infarct related artery NOT stent thrombosis- those will be excluded from the study also acute occlusion of cardiac grafts will be excluded from the study as well
5 LDL- C will be assessed immediately post angiography The patient will be eligible for the trial if the LDL-C levels at the screening blood test is one of the following
18 mmoll if patients are on stable unchanged for 4 weeks before screening treatment with high-intensity statin
23 mmoll in patients previously taking low- or moderate-intensity statin 32 mmoll in patients not on statin treatment
6 Eligible patients will be randomly assigned in a 11 ratio to one of the two groups The control group or the intervention group
7 The control group will receive the standard guidelines directed optimal medical therapy
8 The interventional group will receive Evolocumab 140 mg every 2 weeks in addition to the standard guideline directed optimal medical therapy
9 The optimal medical therapy will include high intensity statin either atorvastatin 40-80 mgday or rosuvastatin 20-40 mg day throughout the study or maximal tolerated statin in both groups the statin dose can be titrated up or down as per the standard clinical practice
10 The study drug will be administered at baseline as early as possible but within 24 hr following hospitalization In our institute patients admitted with STEMI will receive primary percutaneous intervention by default The average time for door to balloon time is around 50 minutes department data Randomization and drug administration is not possible within such a short time in addition consider randomization and drug administration before angiography may results in delay of delivering standard therapy which is of not in the best interest of the patient
11 The randomization will be done immediately after angiography and aim for drug administration within 24 hr of admission
12 Blood samples will be obtained at baseline for assessment of fasting lipids and inflammatory markers
13 All patients recruited for the trial will receive medical treatment for ACS as per the Heart hospital and international guidelines Patients that will be considered for the trial should have received coronary angiography and revascularization percutaneous coronary intervention as per the hospital guidelines
14 Patients not fit or rejected re-vascularization with PCI or patient that will need coronary artery bypass grafting CABG surgery will be excluded from this study
15 Written informed consent will be obtained from all the patients
16 The research team may ask for supervised injection when suspect non-compliance
Information and investigation that will be collected from patient
1 Patient will have blood test Lipid panel Liver function and CRP will be done at 01 2 6 and 12 18 and 24 months
2 Carotid intimal thickening measurement at 0 6 12 24 months
3 Echocardiogram 161224 months
4 OPD Review for clinical evaluation medication side effect Chest pain hospitalization or unplanned PCI at 1236121824 months
Randomization
Participants will be randomly assigned using permuted block design with a computer random number generator the block size is fixed 8 per block with random allocation within the block to either the control group or the interventional group of the patients 4 for each group patient allocation within the block is randomly assigned Once the patient has given consent to be included in the trial heshe is then irreversibly randomized by opening the next sealed envelope within the current block containing hisher assignment
The production of computer-generated sets of random allocations will be done by a research support unit who will not be performing data collection in advance of the start of the study
Sample size calculation
Our study is designed as a superiority trial powered for the primary endpoint The average LDL-D cholesterol of patients admitted with ACS-STEMI to the Heart Hospital was 34 mmol based on calculating the average LDL-C of 150 patients with ACS-STEMI in the past 6 months department Data
Bases on the EVOPACS study above statin alone therapy will reduce the LDL-C by 35 119 mmol while Evolocumab statin combination therapy will reduce LDL-C by 77 261 mmol Expectations for cholesterol-lowering trials were set by the Cholesterol Treatment Trialists Collaborators who reported in 2005 that for each 1 mmolL 386 mgdL reduction in LDL-C cardiovascular events were reduced by a mean of 22 Based on this the expected reduction in cardiovascular event is 26 with statin therapy alone and 57 with Evolocumab statin Assuming 1000 cases of ACS-STEMI present to our emergency department every year and event rate of 17-33 post STEMI patient for those on moderate to high intensity statins at one year 90 power and 5 significance level the sample size was 144 for each arm Accounting for the nature of the country of high travel and dropout nature 20 drop rate was added to the sample size the final sample size for this trial was up rounded to 350 patients originally was 346
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