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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiovascular Diseases; STEMI; NSTEMI
• Intervention / Treatment: Drug: Bempedoic Acid / Ezetimibe Oral Tablet; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Andrew P Ambrosy, MD; Phone Number: 415-271-9703; Email: Andrew.P.Ambrosy@kp.org
• Study Contact Backup: Name: Alan S Go, MD; Phone Number: 510-891-3422; Email: Alan.S.Go@kp.org

Study Locations

• United States
  • California
    • Oakland, California, United States, 94612
      • Kaiser Permanente Northern California Division of Research
      • Contact: Rachel C Thomas, RN; Phone Number: 510-891-3858; Email: Rachel.C.Thomas@kp.org
      • Principal Investigator: Andrew P Ambrosy, MD
      • Principal Investigator: Alan S Go, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the safety and tolerability of BA/E vs. matching placebo following a recent ACS event.	- Proportion (%) of adverse events (AEs) leading to permanent study drug discontinuation and unexpected serious AEs (SAEs) at 12 weeks	0-12 weeks
To explore the clinical effectiveness of BA/E vs. usual care on all-cause and cause-specific morbidity and mortality following a recent ACS event.	- Rate (# of events per 100 person-years) of all-cause mortality (ACM)	0-12 weeks
To explore the clinical effectiveness of BA/E vs. usual care on all-cause and cause-specific morbidity and mortality following a recent ACS event.	- Rate (# of events per 100 person-years) of MACE (3-point) = death due to any cause, MI, and/or stroke/TIA	0-12 weeks
To explore the clinical effectiveness of BA/E vs. usual care on all-cause and cause-specific morbidity and mortality following a recent ACS event.	- Rate (# of events per 100 person-years) of MACE (4-point) = MACE (3-point) + hospitalization for unstable angina	0-12 weeks
To explore the clinical effectiveness of BA/E vs. usual care on all-cause and cause-specific morbidity and mortality following a recent ACS event.	- Rate (# of events per 100 person-years) of MACE (5-point) = MACE (4-point) + any coronary revascularization	0-12 weeks
To explore the clinical effectiveness of BA/E vs. usual care on all-cause and cause-specific morbidity and mortality following a recent ACS event.	- Rate (# of events per 100 person-years) of all-cause emergency department (ED) visits + all-cause hospitalizations	0-12 weeks

Collaborators and Investigators

• Sponsor: Kaiser Permanente
• Collaborators: Esperion Therapeutics, Inc.
• Investigators: Principal Investigator: Andrew P Ambrosy, MD, Kaiser Permanente Northern California Division of Research; Principal Investigator: Alan S Go, MD, Kaiser Permanente Northern California Division of Research

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2022
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: February 14, 2022
• First Submitted That Met QC Criteria: March 1, 2022
• First Posted (Actual): March 3, 2022

Study Record Updates

• Last Update Posted (Actual): March 3, 2022
• Last Update Submitted That Met QC Criteria: March 1, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Vascular Diseases; Cardiovascular Diseases; Acute Coronary Syndrome; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Ezetimibe; 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
• Other Study ID Numbers: 1824539

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No