The Safety and Long-Term Clinical Benefit of PCSK9i in STEMI Patients

NCT05579418 | Unknown Phase 4 DMC

• 1 other identifier: MRC-01-22-366
• Study Type: interventional
• Target: 350
• Locations: 0 countries
• Sites: N/A

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.

Conditions

STEMI; Dyslipidemias

Keywords

STEMI; PCSK9i; Evolocumab; Statin

Outcome Measures

Primary Outcomes (2)

• Major cardiovascular events, defined as the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization.

  The primary objective of this study is to confirm the safety and the long-term clinical benefit associated with the use of PCSK9i in combination with statin in patients with ACS-STEMI. The long terms clinical benefit is the reduction in major cardiovascular events, defined as the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization.

  12 months

• The safety of PCSK9i in patients with STEMI

  The safety of PCSK9i use in patients admitted with STEMI in terms of adverse events and complications related to the use of PCSK9i.

  12 months

Secondary Outcomes (6)

• Percentage change in calculated LDL-C from baseline to end of study period.

  12 months

• Changes in carotid intimal thickening from baseline to the end of study period

  12 months

• Adverse events and serious adverse events reported during study period.

  12 months

• Changes in High-sensitivity C-reactive protein from baseline to the end of study period

  12 months

• Changes in left ventricular ejection fraction from baseline to the end of study period .

  12 months

Study Arms (2)

Interventional Arm

ACTIVE COMPARATOR

Patient that qualify for the trial will be randomized for receiving the PCSK9i injection in addition to the standard medical therapy.

Drug: Evolocumab

Control Arm

NO INTERVENTION

Patient will only receive the standard medical therapy, No PCSK9i

Interventions

Evolocumab DRUG

Evolocumab is an injection for management of dyslipidemia

Also known as: Repatha

Interventional Arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Male or female ≥ 18 years of age and less than 80 years
• Hospitalized for a recent ACS-STEMI within 12 hours of onset of symptoms.
• Successful revascularization with PCI.
• LDL-C levels defined as follows:
• LDL-C ≥1.8 mmol/L in patients who have been receiving stable treatment with high-intensity statin within ≥ 4 weeks prior to enrollment (i.e., continuous treatment that has not changed with regard to statin intensity over the past 4 weeks)
• LDL-C ≥2.3 mmol/L in patients who have been receiving stable treatment with low- or moderate-intensity statin within ≥ 4 weeks prior to enrollment (i.e., continuous treatment that has not changed with regard to statin intensity over the past 4 weeks)
• LDL-C ≥3.2 mmol/L in patients who are statin-naïve or have not been on a stable (unchanged) statin regimen for at least 4 weeks prior to enrollment.
• Ability to understand the requirements of the study and to provide informed consent
• Unstable clinical status (hemodynamic or electrical instability)
• Uncontrolled cardiac arrhythmia, defined as recurrent and symptomatic ventricular tachycardia or atrial fibrillation or flutter with rapid ventricular response not controlled by medications in the past 3 months prior to screening
• Severe renal dysfunction, defined by estimated glomerular filtration rate \<30 ml/min/1.73m2
• Active liver disease or hepatic dysfunction, either reported in patient medical record or defined by aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels \> 3x the upper limit of normal.
• Patient need urgent CABG
• patients symptoms onset is more than 12 hours.
• Reported intolerance to atorvastatin (any dose) OR statin intolerance defined by the following criteria:

Sponsors & Collaborators

• Hamad Medical Corporation: lead

MeSH Terms

Conditions

ST Elevation Myocardial Infarction; Dyslipidemias

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Mohammed Ali, MD

  Hamad Medical Corporation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

MOHAMMED ALI, MD

CONTACT

0097433820545; mali80@hamad.qa

Ahmed Rudwan, MD

CONTACT

0097455461103; arudwan@hamad.qa

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Interventional Cardiologist

Model Details: The study is an investigator-initiated, prospective, randomized, open-label study. 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, 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. 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 (4 for each group, patient allocation within the block is randomly assigned). Once the patient has given consent to be included in the trial, he/she is then irreversibly randomized by opening the next sealed envelope, within the current block, containing his/her assignment.

Study Record Dates

• First Submitted: October 10, 2022
• First Posted: October 13, 2022
• Study Start: November 1, 2022
• Primary Completion: October 30, 2024
• Study Completion: October 30, 2024
• Last Updated: October 13, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 10 years
• Access Criteria: Request has to be approved by PI and Heart Hospital Research Advisory Board.