ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab

Study Overview
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Brief Summary
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Primary Objective: To compare the effect of alirocumab with placebo on the occurrence of cardiovascular (CV) events (composite endpoint of coronary heart disease (CHD) death, non-fatal myocardial infarction (MI), fatal and non-fatal ischemic stroke, unstable angina (UA) requiring hospitalization) in participants who experienced an acute coronary syndrome (ACS) event 4 to 52 weeks prior to randomization and were treated with evidence-based medical and dietary management of dyslipidemia. Secondary Objectives: To evaluate the effect of alirocumab on secondary endpoints (any CHD event , major CHD event, any CV event, composite of all cause mortality/non-fatal MI/non-fatal ischemic stroke, CHD deaths, CV deaths, all cause mortality). To evaluate the safety and tolerability of alirocumab. To evaluate the effect of alirocumab on lipid parameters.

Detailed Description
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18924 number of participants aged >= 40 years old were randomized in the study.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Effect of Alirocumab (SAR236553/REGN727) on the Occurrence of Cardiovascular Events in Patients Who Have Recently Experienced an Acute Coronary Syndrome

Conditions
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Atherosclerotic Cardiovascular Disease

Intervention / Treatment
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* Drug: Alirocumab
* Drug: Placebo
* Drug: LMT


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Recently (< 52 weeks) hospitalized for ACS. Exclusion criteria: Age < 40 years. ACS event occurring more than 52 weeks prior to randomization visit. LDL-C likely to be <70 mg/dL (<1.81 mmo/L), and apolipoprotein B (ApoB) <80 mg/dL (<0.8 g/L), and non - high-density lipoprotein cholesterol (HDL-C) <100 mg/dL (<2.59 mmol/L) with evidence-based medical and dietary management of dyslipidemia. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 40 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo (for alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable Lipid-Modifying Therapy (LMT) for up to 64 months. | Drug: Placebo<br>* Placebo matched to alirocumab administered as a SC injection of 1 mL in the abdomen or thigh with a disposable auto-injector.<br>Drug: LMT<br>* Statins (atorvastatin or rosuvastatin) at stable maximal tolerated dose of statin with or without other LMT as clinically indicated.<br>|
| Experimental: Alirocumab 75 mg Q2W/Up to 150 mg Q2W<br>Alirocumab 75 mg SC injection Q2W added to stable LMT for up to 64 months. Alirocumab dose up-titrated to 150 mg Q2W from Month 2 when Low-Density Lipoprotein Cholesterol (LDL-C) levels >=50 mg/dL (1.29 mmol/L) at Month 1; or if up-titration was missed due to unavailability of LDL-C value, it was up-titrated at month 4 based on LDL-C value at Month 2. For participants receiving 150 mg Q2W, alirocumab dose was down-titrated in a blinded manner to 75 mg Q2W if two consecutive values of LDL-C were <25 mg/dL (0.65 mmol/L). For participants receiving 75 mg Q2W, alirocumab dose was switched to placebo in a blinded manner if two consecutive values of LDL-C were <15 mg/dL (0.39 mmol/L). | Drug: Alirocumab<br>* Alirocumab administered as SC injection of 1 mL in the abdomen or thigh with a disposable auto-injector.<br>* Other names: Praluent®;Drug: LMT<br>* Statins (atorvastatin or rosuvastatin) at stable maximal tolerated dose of statin with or without other LMT as clinically indicated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Occurrence of Major Adverse Cardiovascular Event (MACE); Percentage of Observed Participants With Outcome Measure Events During the Study | All MACE positively adjudicated by Clinical Events Committee (CEC) in a blinded fashion, were used in the analysis of the composite cardiovascular (CV) outcome measure comprised of Coronary Heart Disease (CHD) death, non-fatal Myocardial Infarction (MI), fatal and non-fatal ischemic stroke (IS), or unstable angina (UA) requiring hospitalization. Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict the first occurrence of MACE over time. Percentage of observed participants with outcome measure events during the study were reported. | From randomization up to 64 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Occurrence of Any Coronary Heart Disease Event; Percentage of Observed Participants With Outcome Measure Events During the Study | All CHD events positively adjudicated by CEC in a blinded fashion, were used in the analysis of the composite CHD endpoint comprised of any CHD death, non-fatal non-fatal MI, UA requiring hospitalization, or ischemia-driven coronary revascularization procedure. Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict the first occurrence of any CHD event over time. Percentage of observed participants with outcome measure events during the study were reported. | From randomization up to 64 months | 
| Time to First Occurrence of Any Major Coronary Heart Disease Event; Percentage of Observed Participants With Outcome Measure Events During the Study | All Major CHD events positively adjudicated by CEC in a blinded fashion, were used in the analysis of the composite CHD endpoint comprised of any CHD death and non-fatal MI. Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict the first occurrence of any major CHD event over time. Percentage of observed participants with outcome measure events during the study were reported. | From randomization up to 64 months | 
| Time to First Occurrence of Any Cardiovascular Event; Percentage of Observed Participants With Outcome Measure Events During the Study | All CV events positively adjudicated by CEC in a blinded fashion, were used in the analysis of the composite CV endpoint comprised of any non-fatal CHD event, any CV death and non-fatal IS. Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict the first occurrence of any CV event over time. Percentage of observed participants with outcome measure events during the study were reported. | From randomization up to 64 months | 
| Time to First Occurrence of All-Cause Mortality, Non-Fatal Myocardial Infarction, Non-Fatal Ischemic Stroke; Percentage of Observed Participants With Outcome Measure Events During the Study | All-cause mortality, non-fatal MI and non-fatal IS positively adjudicated by CEC in a blinded fashion, were used in the analysis of this endpoint. Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict the first occurrence of all-cause mortality, non-fatal MI and non-fatal IS over time. Percentage of observed participants with outcome measure events during the study were reported. | From randomization up to 64 months | 
| Time to Coronary Heart Disease Death; Percentage of Observed Participants With Outcome Measure Events During the Study | Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict the CHD death over time. Percentage of observed participants with CHD death (positively adjudicated by CEC in a blinded fashion) were reported. | From randomization up to 64 months | 
| Time to Cardiovascular Death; Percentage of Observed Participants With Outcome Measure Events During the Study | Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict the CV death over time. Percentage of observed participants with CV death (positively adjudicated by CEC in a blinded fashion) were reported. | From randomization up to 64 months | 
| Time to All-Cause Death; Percentage of Observed Participants With Outcome Measure Events During the Study | Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict the all-cause death over time. Percentage of observed participants with all-cause death (positively adjudicated by CEC in a blinded fashion) were reported. | From randomization up to 64 months | 
| Time to First Occurrence of Any Non-Fatal Myocardial Infarction; Percentage of Observed Participants With Outcome Measure Events During the Study | Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict the first occurrence of any non-fatal MI over time. Percentage of observed participants with any non-fatal MI (positively adjudicated by CEC in a blinded fashion) were reported. | From randomization up to 64 months | 
| Time to First Occurrence of Fatal or Any Non-Fatal Ischemic Stroke; Percentage of Observed Participants With Outcome Measure Events During the Study | Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict the first occurrence of fatal or any non-fatal IS over time. Percentage of observed participants with fatal or any non-fatal IS (positively adjudicated by CEC in a blinded fashion) were reported. | From randomization up to 64 months | 
| Time to First Occurrence of Any Unstable Angina Requiring Hospitalization; Percentage of Observed Participants With Outcome Measure Events During the Study | Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict the first occurrence of any UA requiring hospitalization over time. Percentage of observed participants with any UA requiring hospitalization (positively adjudicated by CEC in a blinded fashion) were reported. | From randomization up to 64 months | 
| Time to First Occurrence of Any Ischemia-Driven Coronary Revascularization Procedure; Percentage of Observed Participants With Outcome Measure Events During the Study | Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict the first occurrence of any ischemia-driven coronary revascularization procedure over time. Percentage of observed participants with any ischemia-driven coronary revascularization procedure (positively adjudicated by CEC in a blinded fashion) were reported. | From randomization up to 64 months | 
| Time to First Occurrence of Any Congestive Heart Failure (CHF) Requiring Hospitalization; Percentage of Observed Participants With Outcome Measure Events During the Study | Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict the first occurrence of any CHF requiring hospitalization over time. Percentage of observed participants with any CHF requiring hospitalization (positively adjudicated by CEC in a blinded fashion) were reported. | From randomization up to 64 months |