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

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ClinicalTrials.gov Identifier: NCT01663402
Recruitment Status : Completed
First Posted : August 13, 2012
Results First Posted : March 18, 2019
Last Update Posted : March 18, 2019
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Study Description
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Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Atherosclerotic Cardiovascular Disease Drug: Alirocumab Drug: Placebo Drug: LMT Phase 3

Detailed Description:
18924 number of participants aged >= 40 years old were randomized in the study.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18924 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: 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
Actual Study Start Date : October 2012
Actual Primary Completion Date : January 23, 2018
Actual Study Completion Date : January 23, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Alirocumab

Arms and Interventions
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Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo (for alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable Lipid-Modifying Therapy (LMT) for up to 64 months.
 Drug: Placebo
Placebo matched to alirocumab administered as a SC injection of 1 mL in the abdomen or thigh with a disposable auto-injector.

Drug: LMT
Statins (atorvastatin or rosuvastatin) at stable maximal tolerated dose of statin with or without other LMT as clinically indicated.
Experimental: Alirocumab 75 mg Q2W/Up to 150 mg Q2W
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
Alirocumab administered as SC injection of 1 mL in the abdomen or thigh with a disposable auto-injector.
Other Names:
  • SAR236553
  • REGN727
  • Praluent®

Drug: LMT
Statins (atorvastatin or rosuvastatin) at stable maximal tolerated dose of statin with or without other LMT as clinically indicated.


Outcome Measures
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Primary Outcome Measures :
  1. Time to First Occurrence of Major Adverse Cardiovascular Event (MACE); Percentage of Observed Participants With Outcome Measure Events During the Study [ Time Frame: From randomization up to 64 months ]
    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.


Secondary Outcome Measures :
  1. Time to First Occurrence of Any Coronary Heart Disease Event; Percentage of Observed Participants With Outcome Measure Events During the Study [ Time Frame: From randomization up to 64 months ]
    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.

  2. Time to First Occurrence of Any Major Coronary Heart Disease Event; Percentage of Observed Participants With Outcome Measure Events During the Study [ Time Frame: From randomization up to 64 months ]
    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.

  3. Time to First Occurrence of Any Cardiovascular Event; Percentage of Observed Participants With Outcome Measure Events During the Study [ Time Frame: From randomization up to 64 months ]
    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.

  4. 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 [ Time Frame: From randomization up to 64 months ]
    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.

  5. Time to Coronary Heart Disease Death; Percentage of Observed Participants With Outcome Measure Events During the Study [ Time Frame: From randomization up to 64 months ]
    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.

  6. Time to Cardiovascular Death; Percentage of Observed Participants With Outcome Measure Events During the Study [ Time Frame: From randomization up to 64 months ]
    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.

  7. Time to All-Cause Death; Percentage of Observed Participants With Outcome Measure Events During the Study [ Time Frame: From randomization up to 64 months ]
    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.

  8. Time to First Occurrence of Any Non-Fatal Myocardial Infarction; Percentage of Observed Participants With Outcome Measure Events During the Study [ Time Frame: From randomization up to 64 months ]
    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.

  9. Time to First Occurrence of Fatal or Any Non-Fatal Ischemic Stroke; Percentage of Observed Participants With Outcome Measure Events During the Study [ Time Frame: From randomization up to 64 months ]
    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.

  10. Time to First Occurrence of Any Unstable Angina Requiring Hospitalization; Percentage of Observed Participants With Outcome Measure Events During the Study [ Time Frame: From randomization up to 64 months ]
    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.

  11. Time to First Occurrence of Any Ischemia-Driven Coronary Revascularization Procedure; Percentage of Observed Participants With Outcome Measure Events During the Study [ Time Frame: From randomization up to 64 months ]
    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.

  12. Time to First Occurrence of Any Congestive Heart Failure (CHF) Requiring Hospitalization; Percentage of Observed Participants With Outcome Measure Events During the Study [ Time Frame: From randomization up to 64 months ]
    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.


Other Outcome Measures:
  1. Percent Change From Baseline in Calculated LDL-C at Months 4, 12, and 48: ITT Analysis [ Time Frame: Baseline, Months 4, 12 and 48 ]
    Adjusted means and standard errors at Month 4, 12 and 48 from multiple imputation approach (to account for missing data) followed by analyses of covariance (ANCOVA) model with the fixed categorical effect of treatment group and the continuous fixed covariate of baseline LDL-C value, including all available post-baseline data from Month 1 up to Month 48 regardless of status on- or off-treatment.

  2. Percent Change From Baseline in Calculated LDL-C at Months 4, 12, and 48: On-Treatment Analysis [ Time Frame: Baseline, Months 4, 12 and 48 ]
    Adjusted Least-squares (LS) means and standard errors at Month 4, 12 and 48 were obtained from a mixed-effect model with repeated measures (MMRM) including available post-baseline on-treatment data from Month 1 up to Month 48 (i.e. up to 21 days after last injection).


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01663402


Locations
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Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
  Study Documents (Full-Text)

Documents provided by Sanofi:
Study Protocol  [PDF] February 25, 2016
Statistical Analysis Plan  [PDF] October 11, 2017

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01663402    
Other Study ID Numbers: EFC11570
2011-005698-21 ( EudraCT Number )
U1111-1127-4323 ( Other Identifier: UTN )
First Posted: August 13, 2012    Key Record Dates
Results First Posted: March 18, 2019
Last Update Posted: March 18, 2019
Last Verified: March 2019
Additional relevant MeSH terms:
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Cardiovascular Diseases
Acute Coronary Syndrome
Atherosclerosis
Myocardial Ischemia
Heart Diseases
Vascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Alirocumab
 PCSK9 Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Lipid Regulating Agents