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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

Tracking Information
First Submitted Date  ICMJE August 8, 2012
First Posted Date  ICMJE August 13, 2012
Results First Submitted Date  ICMJE January 21, 2019
Results First Posted Date  ICMJE March 18, 2019
Last Update Posted Date March 18, 2019
Actual Study Start Date  ICMJE October 2012
Actual Primary Completion Date January 23, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 15, 2019)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 10, 2012)
Time from randomization to first occurrence of one of the following clinical events: CHD death, any non-fatal MI, fatal and non-fatal ischemic stroke, unstable angina requiring hospitalization [ Time Frame: Up to Month 64 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 15, 2019)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 10, 2012)
  • Time to the first occurrence of any CHD event, major CHD event, any CV event, composite of all cause mortality/non-fatal MI/non-fatal ischemic stroke, all cause mortality [ Time Frame: Up to Month 64 ]
  • Change from baseline in blood lipids and lipoprotein levels [ Time Frame: Up to Month 64 ]
  • Number of patients with adverse events [ Time Frame: Up to Month 64 ]
Current Other Pre-specified Outcome Measures
 (submitted: March 15, 2019)
  • 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.
  • 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).
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab
Official Title  ICMJE 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
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.
Detailed Description 18924 number of participants aged >= 40 years old were randomized in the study.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE Atherosclerotic Cardiovascular Disease
Intervention  ICMJE
  • 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: 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.
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Placebo
    • Drug: LMT
  • 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).
    Interventions:
    • Drug: Alirocumab
    • Drug: LMT
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 15, 2019)
18924
Original Estimated Enrollment  ICMJE
 (submitted: August 10, 2012)
18000
Actual Study Completion Date  ICMJE January 23, 2018
Actual Primary Completion Date January 23, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Bosnia and Herzegovina,   Brazil,   Bulgaria,   Canada,   Chile,   China,   Colombia,   Croatia,   Czechia,   Denmark,   Estonia,   Finland,   France,   Georgia,   Germany,   Greece,   Guatemala,   Hong Kong,   Hungary,   India,   Israel,   Italy,   Japan,   Korea, Republic of,   Latvia,   Lithuania,   Macedonia, The Former Yugoslav Republic of,   Malaysia,   Mexico,   Netherlands,   New Zealand,   Norway,   Peru,   Philippines,   Poland,   Portugal,   Romania,   Russian Federation,   Serbia,   Singapore,   Slovakia,   Slovenia,   South Africa,   Spain,   Sri Lanka,   Sweden,   Switzerland,   Taiwan,   Thailand,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01663402
Other Study ID Numbers  ICMJE EFC11570
2011-005698-21 ( EudraCT Number )
U1111-1127-4323 ( Other Identifier: UTN )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Regeneron Pharmaceuticals
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP