Cholesterol Lowering Via Bempedoic Acid/Ezetimibe, an ACL-Inhibiting Regimen in Acute Coronary Syndrome Study

Study Overview
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Brief Summary
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The overall objective of the Cholesterol Lowering via Bempedoic Acid/Ezetimibe, an ACL-Inhibiting Regimen in Acute Coronary Syndrome ACS (CLEAR ACS) study is to determine the efficacy, safety, and tolerability of bempedoic acid/ezetimibe (BA/E) in a contemporary and real-world population, enriched for older adults, women, and underrepresented racial/ethnic groups, of adults with a recent acute coronary syndrome (ACS) event independent of use of statin therapy before the ACS event.

Detailed Description
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The CLEAR ACS study is a prospective, virtual, electronic health record (EHR)-based, randomized, double-blind, placebo-controlled, parallel-group, pragmatic clinical trial (PCT) embedded within Kaiser Permanente Northern California's fully integrated and learning health care delivery system. The EHR will be screened in real-time for potentially eligible participants across all Kaiser Permanente Northern California hospitals using validated diagnostic and procedural codes, disease registries, laboratory values, pharmacy dispensing information, and sociodemographic data sources. Eligible patients that provide informed consent will be randomized in a 1:1 allocation ratio to an initial 12 weeks of blinded bempedoic acid/ezetimibe (BA/E) vs. matching placebo followed by a 12-week open-label extension phase where all patients will receive open-label, unblinded bempedoic acid/ezetimibe.

Official Title
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Cholesterol Lowering Via Bempedoic Acid/Ezetimibe, an ACL-Inhibiting Regimen in Acute Coronary Syndrome (CLEAR ACS) Study

Conditions
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Cardiovascular Diseases, NSTEMI, STEMI

Intervention / Treatment
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* Drug: Bempedoic Acid / Ezetimibe Oral Tablet
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women age >18 years Able to provide informed consent A documented recent ACS event (i.e., defined as up to 14 days post-discharge from an index hospitalization for a non-ST-elevation MI [NSTEMI] or ST-elevation MI [STEMI] necessitating urgent and/or emergent percutaneous coronary intervention [PCI] and/or coronary after bypass graft [CABG]) At least 6 months of continuous health plan membership and prescription drug benefit prior to enrollment A registered e-mail address with Kaiser Permanente in order to obtain electronic consent (eConsent) for study participation Exclusion Criteria: Receipt of BA/E on or within 3 months before the day of enrollment A history of hypersensitivity to BA/E Women who are pregnant or planning to become pregnant and/or breastfeeding mothers A diagnosis of gout and/or previously known laboratory-confirmed hyperuricemia (serum uric acid >8.0 mg/dL) A history of tendon disorders or tendon rupture Current and/or planned treatment with simvastatin/pravastatin, cyclosporine, fibrates, and/or bile acid sequestrants (to avoid drug-drug interactions) A known life-limiting diagnosis (e.g., stage D heart failure, severe liver disease, end-stage kidney disease [ESKD] requiring chronic dialysis or an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2, metastatic cancer and/or actively receiving systemic chemotherapy) Institutionalized and/or receiving palliative care Non-English speaking

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Pragmatic randomized clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention<br>Bempedoic acid 180 mg/ezetimibe 10 mg | Drug: Bempedoic Acid / Ezetimibe Oral Tablet<br>* Bempedoic acid 180 mg/ezetimibe 10 mg by mouth once daily for 12 weeks<br>* Other names: Nexlizet;|
| Placebo Comparator: Placebo<br>Matching placebo | Drug: Placebo<br>* Matching placebo by mouth once daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the efficacy of BA/E vs. matching placebo on LDL-C level following a recent ACS event. | Percent (%) change from baseline to week 12 in LDL-C level | 0-12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the efficacy of BA/E vs. matching placebo on the lipid profile following a recent ACS event. | - Percent (%) change from baseline to week 12 in high-density lipoprotein cholesterol (HDL-C) | 0-12 weeks | 
| To determine the efficacy of BA/E vs. matching placebo on the lipid profile following a recent ACS event. | - Percent (%) change from baseline to week 12 in non-HDL-C | 0-12 weeks | 
| To determine the efficacy of BA/E vs. matching placebo on the lipid profile following a recent ACS event. | - Percent (%) change from baseline to week 12 in total cholesterol (TC) | 0-12 weeks | 
| To determine the efficacy of BA/E vs. matching placebo on the lipid profile following a recent ACS event. | - Percent (%) change from baseline to week 12 in triglyceride (TGs) levels | 0-12 weeks |