Ezetimibe Utilization Early After Acute Myocardial Infarction, "EzAMI Trial"

NCT04701242 | Recruiting

• 1 other identifier: 20200902MYFAHC_EzAMI
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: Patients with acute coronary syndromes are at an increased risk for recurrent adverse coronary events, particularly during the early period following their initial presentation. Early (in-hospital) initiation of high-intensity statins reduces the risk of recurrent events and is therefore recommended by the best current practice guidelines.(1,2) However, the delayed onset of action of statin therapy and given the frequent failure of patients to achieve the recommended LDL-C targets using statins alone (as per the current practice guidelines recommendations), might be placing large number of patients at increased risk during such a vulnerable period early after an ACS.(3) More rapid and effective reduction of LDL-C levels using combination therapy from the outset may therefore be beneficial in these patients. This hypothesis has been tested with combining Evolocumab and a statin in the recent EVOPACS study, in which this combination after ACS has shown to be safe and more effective in achieving LDL-C targets at 6 weeks compared to statin monotherapy.(4) However, Evolocumab (a PCSK9i) is an expensive drug which is not affordable by many healthcare systems in low- and middle-income countries. Ezetemibe, on the other hand, is a safe and a cheap drug that can prove to be extremely cost-effective if a meaningful and timely reduction in LDL-C levels can be achieved when combined with a statin early after an ACS. Study population Patients presenting with acute myocardial infarction, with baseline LDL-C levels not likely to achieve recommended targets on statin monotherapy. This is assumed to be with LDL-C level \> 125 mg/dl for those not on lipid lowering therapy; or with LDL-C \> 100 mg/dl on moderate intensity statin therapy at the time of presentation. Study design Prospective randomized controlled single-blinded trial. A sample size of 500 patients, 250 in each arm, was calculated to provide a power of 0.9 and an adjusted type 1 error as 0.05. Primary outcomes

• Percentage of patients achieving target LDL-C levels (\<70 mg/dl) at 6 weeks interval. (Efficacy endpoint)
• Freedom from alanine transaminase elevation (ALT) more than 3 folds upper reference limit "URL" or statin associated muscle symptoms associated with CK elevation more than 4 folds URL. (Safety endpoint) Secondary outcomes
• Percentage of patients achieving \> 50% reduction of LDL-C and to levels below 70mg/dl at 6 weeks interval.
• Percentage of LDL-C reduction at 6 weeks interval.
• Reduction of high-sensitive C-reactive protein (hs-CRP) from baseline to 6 weeks interval.
• Correlating statins efficacy to reduce LDL-C and likelihood to cause statins related adverse effects to genetic alleles of ABC \[ATP Binding Cassette\] types A1, G5 and G8, and of CYP450 isoenzymes.
• MACE free survival at 1 year, (CV death; non fatal-MI; hospitalization for ACS, urgent unplanned revascularization and stroke).

Conditions

Acute Myocardial Infarction; Dyslipidemias

Keywords

Statin failure, acute myocardial infarction, ezetimibe

Outcome Measures

Primary Outcomes (2)

• Efficacy endpoint

  ● Percent of patients who achieve required LDL-C targets according to the ACC guidelines (\<70 mg/dl) at 6 weeks interval.

  Six weeks

• (Safety endpoint)

  ● Freedom from Alanine Transaminase elevation (ALT) more than 3 folds upper reference limit OR muscle pains associated with CK elevation more than 4 folds upper reference limit.

  Six weeks

Secondary Outcomes (3)

• ● Percent of LDL-C reduction from baseline to 6 weeks interval.

  Six weeks

• ● Reduction of high-sensitive C-reactive protein (hs-CRP) from baseline to 6 weeks interval.

  Six weeks

• ● MACE free survival at 1 year, (cardiovascular death; non fatal-MI; hospitalization for ACS, urgent unplanned revascularization, and cerebrovascular stroke)

  One year

Study Arms (2)

Atorvastatin-Ezetimibe combination

ACTIVE COMPARATOR

Eligible patients randomized to this arm will receive combination of Atorvastatin 80mg plus Ezetimibe 10mg

Drug: Ezetimibe 10mg

Atorvastatin monotherapy

NO INTERVENTION

Eligible patients randomized to this arm will receive Atorvastatin 80mg as monotherapy for LDL-C reduction. They can be upgraded to combination (adding Ezetimibe 10mg) if found in follow-up that they had not achieve recommended LDL-C targets.

Interventions

Ezetimibe 10mg DRUG

comparing upfront use of Ezetimibe (added to high intensity statins) after acute myocardial infarction versus selective Ezetimibe initiation to those failing to achieve LDL-C targets when assessed in follow up visit.

Atorvastatin-Ezetimibe combination

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age more than 18 years. Both genders are eligible.
• Acute myocardial infarction (STEMI or NSTEMI) within 48 hours from the onset of symptoms.
• Baseline LDL-C above 125 mg/dl for those who were not on consistent lipid lowering therapy; or above 100 mg/dl for those who were compliant (≥ 90 days) on moderate intensity statin therapy.

You may not qualify if:

• Refusal to participate in the study.
• Proved intolerance to statins on previous use.
• Having conditions (or taking medications) that would not allow concomitant safe statins use. \[such as patients receiving Cyclosporine - Gemfibrozil -Pazopanib - Tipranavir - Itraconazole - Ketoconazole\]
• Those who are already compliant on high intensity statins.
• Those who are already on statins plus non-statin agent (ezetimibe-PCSK9i-BAS).
• Known familial dyslipidemia or having TG\>500 mg/dl or LDL-C\>190 mg/dl which are highly suggestive of familial or secondary causes.
• Pregnant or contemplating pregnancy in the following 12 months. \[relevant for females in the child-bearing period\]

Sponsors & Collaborators

• Cairo University: lead
• Aswan Heart Centre: collaborator

Study Sites (1)

Aswan Heart Centre

Aswān, 81511, Egypt

RECRUITING

MeSH Terms

Conditions

Dyslipidemias

Interventions

Ezetimibe

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ahmad Samir, MD

  Cairo University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ahmad Samir, MD

CONTACT

00201002647275; ahmad.samir@kasralainy.edu.eg

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Participants will receive blinded drug containers. Care providers and investigators assessing study end-points will be blinded to group allocation of the patients Steering committee will be the only who have the key table for study-ID of the patient and allocation groups.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer of Cardiology

Model Details: Double blinded, randomized controlled trial 1:1 randomization

Study Record Dates

• First Submitted: January 6, 2021
• First Posted: January 8, 2021
• Study Start: March 24, 2021
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: August 21, 2024

Record last verified: 2024-08

Locations

EG (1)