Evaluation of Effect of Alirocumab on Coronary Atheroma Volume in Japanese Patients Hospitalized for Acute Coronary Syndrome With Hypercholesterolemia
- Conditions
- HypercholesterolemiaAcute Coronary Syndrome
- Interventions
- Registration Number
- NCT02984982
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
To compare the efficacy of alirocumab (Praluent®) with standard of care (SoC) on coronary atheroma progression (percent change in normalized total atheroma volume \[TAV\]) after 9 months of treatment in participants who had acute coronary syndrome (ACS) within 4 weeks prior to randomization, with hypercholesterolemia treated with statin.
Secondary Objectives:
* To compare the efficacy of alirocumab (Praluent®) with SoC on secondary endpoints including absolute change in percent atheroma volume and normalized TAV after 9 months of treatment.
* To evaluate the efficacy of alirocumab (Praluent®) on low-density lipoprotein cholesterol (LDL-C), apolipoprotein B, triglycerides, non-high-density lipoprotein cholesterol and lipoprotein (a) after 9 months treatment.
* To evaluate the safety of alirocumab (Praluent®) including the occurrence of cardiovascular events (coronary heart disease death, non-fatal myocardial infarction, fatal and non-fatal ischemic stroke, unstable angina requiring hospitalization) throughout the study.
- Detailed Description
The duration of study per participant was 9 months.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 206
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard of Care Fenofibrate Statin therapy (atorvastatin or rosuvastatin) will be administered with or without non-statin lipid modifying therapies (LMTs). Non-statin LMTs will be adjusted by physicians to achieve the LDL-C target level \<100 milligrams per deciliter (mg/dL). Standard of Care Bezafibrate Statin therapy (atorvastatin or rosuvastatin) will be administered with or without non-statin lipid modifying therapies (LMTs). Non-statin LMTs will be adjusted by physicians to achieve the LDL-C target level \<100 milligrams per deciliter (mg/dL). Standard of Care Ezetimibe Statin therapy (atorvastatin or rosuvastatin) will be administered with or without non-statin lipid modifying therapies (LMTs). Non-statin LMTs will be adjusted by physicians to achieve the LDL-C target level \<100 milligrams per deciliter (mg/dL). Standard of Care Antiplatelets Statin therapy (atorvastatin or rosuvastatin) will be administered with or without non-statin lipid modifying therapies (LMTs). Non-statin LMTs will be adjusted by physicians to achieve the LDL-C target level \<100 milligrams per deciliter (mg/dL). Standard of Care Anticoagulants Statin therapy (atorvastatin or rosuvastatin) will be administered with or without non-statin lipid modifying therapies (LMTs). Non-statin LMTs will be adjusted by physicians to achieve the LDL-C target level \<100 milligrams per deciliter (mg/dL). Alirocumab Alirocumab SAR236553 Alirocumab will be given subcutaneously every 2 weeks on top of stable dose statin therapy (atorvastatin or rosuvastatin) with or without stable dose non-statin LMTs. Alirocumab Atorvastatin Alirocumab will be given subcutaneously every 2 weeks on top of stable dose statin therapy (atorvastatin or rosuvastatin) with or without stable dose non-statin LMTs. Alirocumab Rosuvastatin Alirocumab will be given subcutaneously every 2 weeks on top of stable dose statin therapy (atorvastatin or rosuvastatin) with or without stable dose non-statin LMTs. Alirocumab Fenofibrate Alirocumab will be given subcutaneously every 2 weeks on top of stable dose statin therapy (atorvastatin or rosuvastatin) with or without stable dose non-statin LMTs. Alirocumab Bezafibrate Alirocumab will be given subcutaneously every 2 weeks on top of stable dose statin therapy (atorvastatin or rosuvastatin) with or without stable dose non-statin LMTs. Alirocumab Ezetimibe Alirocumab will be given subcutaneously every 2 weeks on top of stable dose statin therapy (atorvastatin or rosuvastatin) with or without stable dose non-statin LMTs. Alirocumab Antiplatelets Alirocumab will be given subcutaneously every 2 weeks on top of stable dose statin therapy (atorvastatin or rosuvastatin) with or without stable dose non-statin LMTs. Alirocumab Anticoagulants Alirocumab will be given subcutaneously every 2 weeks on top of stable dose statin therapy (atorvastatin or rosuvastatin) with or without stable dose non-statin LMTs. Standard of Care Rosuvastatin Statin therapy (atorvastatin or rosuvastatin) will be administered with or without non-statin lipid modifying therapies (LMTs). Non-statin LMTs will be adjusted by physicians to achieve the LDL-C target level \<100 milligrams per deciliter (mg/dL). Standard of Care Atorvastatin Statin therapy (atorvastatin or rosuvastatin) will be administered with or without non-statin lipid modifying therapies (LMTs). Non-statin LMTs will be adjusted by physicians to achieve the LDL-C target level \<100 milligrams per deciliter (mg/dL).
- Primary Outcome Measures
Name Time Method Percent Change From Baseline in Normalized Total Atheroma Volume (TAV) at Week 36 Baseline, Week 36 Least-squares (LS) means and standard errors (SE) at Week 36 were obtained from analysis of covariance (ANCOVA) model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and the baseline normalized TAV as continuous fixed covariate.
- Secondary Outcome Measures
Name Time Method Absolute Change From Baseline in External Elastic Membrane (EEM) Volume at Week 36 Baseline, Week 36 Adjusted mean and SE at Week 36 were obtained from robust regression model with treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]), as fixed categorical effects, and the baseline EEM volume value as continuous fixed covariate.
Absolute Change From Baseline in Apolipoprotein B (Apo B) at Week 36 Baseline, Week 36 Adjusted LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and baseline Apo B value as continuous fixed covariate.
Percent Change From Baseline in Apolipoprotein B at Week 36 Baseline, Week 36 Adjusted LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and baseline Apo B value as continuous fixed covariate.
Absolute Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 36 Baseline, Week 36 Adjusted LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline calculated non-HDL-C value and baseline calculated non-HDL-C value-by-time point interaction as continuous fixed covariates.
Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol at Week 36 Baseline, Week 36 Adjusted LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline calculated non-HDL-C value and baseline calculated non-HDL-C value-by-time point interaction as continuous fixed covariates.
Absolute Change From Baseline in Total Cholesterol (TC) at Week 36 Baseline, Week 36 LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline calculated TC value and baseline calculated TC value-by-time point interaction as continuous fixed covariates.
Percent Change From Baseline in Total Cholesterol at Week 36 Baseline, Week 36 Adjusted LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline TC value and baseline TC value-by-time point interaction as continuous fixed covariates.
Absolute Change From Baseline in Lipoprotein (a) (Lp[a]) at Week 36 Baseline, Week 36 Adjusted mean and SE at Week 36 were obtained from robust regression model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effect, and baseline Lp(a) value as continuous fixed covariate.
Absolute Change From Baseline in Percent Atheroma Volume (PAV) at Week 36 Baseline, Week 36 LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and the baseline PAV as continuous fixed covariate.
Absolute Change From Baseline in Normalized Total Atheroma Volume at Week 36 Baseline, Week 36 LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and the baseline normalized TAV as continuous fixed covariate.
Absolute Change From Baseline in Lumen Volume at Week 36 Baseline, Week 36 Adjusted mean and SE at Week 36 were obtained from robust regression model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and the baseline lumen volume value as continuous fixed covariate.
Percent Change From Baseline in Calculated Low-density Lipoprotein Cholesterol at Week 12 and Week 36 Baseline, Week 12, Week 36 Adjusted LS mean and SE at Week 12 and Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline calculated LDL-C value and baseline calculated LDL-C value-by-time point interaction as continuous fixed covariates.
Percent Change From Baseline in Fasting Triglycerides at Week 36 Baseline, Week 36 Adjusted mean and SE were obtained by multiple imputation approach followed by robust regression model included fixed categorical effect of treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) and the continuous fixed covariate of baseline fasting TGs value.
Absolute Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 36 Baseline, Week 36 Adjusted LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and baseline Apo A-1 value as continuous fixed covariate.
Percent Change From Baseline in External Elastic Membrane Volume at Week 36 Baseline, Week 36 Adjusted mean and SE at Week 36 were obtained from robust regression model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and the baseline EEM volume value as continuous fixed covariate.
Percent Change From Baseline in Lumen Volume at Week 36 Baseline, Week 36 Adjusted mean and SE at Week 36 were obtained from robust regression model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effect, and the baseline lumen volume value as continuous fixed covariate.
Percent Change From Baseline in Apolipoprotein A-1 at Week 36 Baseline, Week 36 Adjusted LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and baseline Apo A-1 value as continuous fixed covariate.
Absolute Change From Baseline in Calculated Low-density Lipoprotein Cholesterol at Week 12 and Week 36 Baseline, Week 12, Week 36 Adjusted LS mean and SE at Week 12 and Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline calculated LDL-C value and baseline calculated LDL-C value-by-time point interaction as continuous fixed covariates.
Percent Change From Baseline in Lipoprotein (a) at Week 36 Baseline, Week 36 Adjusted mean and SE at Week 36 were obtained from robust regression model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effect, and baseline Lp(a) value as continuous fixed covariate.
Absolute Change From Baseline in High-density Lipoprotein Cholesterol at Week 36 Baseline, Week 36 Adjusted LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline HDL-C value and baseline HDL-C value-by-time point interaction as continuous fixed covariates.
Percent Change From Baseline in High-density Lipoprotein Cholesterol at Week 36 Baseline, Week 36 Adjusted LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline HDL-C value and baseline HDL-C value-by-time point interaction as continuous fixed covariates.
Absolute Change From Baseline in Fasting Triglycerides (TGs) at Week 36 Baseline, Week 36 Adjusted mean and SE were obtained from multiple imputation approach followed by robust regression model including fixed categorical effect of treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) and the continuous fixed covariate of baseline fasting TGs value.
Number of Participants With Cardiovascular (CV) Adverse Events Up to 36 weeks The suspected or confirmed CV events that occurred from randomization until end of the study visit were collected and reported. The various CV events included CV death, myocardial infarction, ischemic stroke, unstable angina requiring hospitalization , congestive heart failure requiring hospitalization, congestive heart failure requiring hospitalization, ischemia-driven coronary revascularization procedure.
Trial Locations
- Locations (39)
Investigational Site Number 392008
🇯🇵Gifu-shi, Japan
Investigational Site Number 392022
🇯🇵Chiyoda-ku, Japan
Investigational Site Number 392039
🇯🇵Hiroshima-shi, Japan
Investigational Site Number 392028
🇯🇵Isehara-shi, Japan
Investigational Site Number 392036
🇯🇵Itabashi-ku, Japan
Investigational Site Number 392037
🇯🇵Itabashi-ku, Japan
Investigational Site Number 392013
🇯🇵Izunokuni-shi, Japan
Investigational Site Number 392009
🇯🇵Kitakyushu-shi, Japan
Investigational Site Number 392034
🇯🇵Kitakyushu-shi, Japan
Investigational Site Number 392044
🇯🇵Kochi-shi, Japan
Investigational Site Number 392003
🇯🇵Kurashiki-shi, Japan
Investigational Site Number 392018
🇯🇵Matsuyama-shi, Japan
Investigational Site Number 392047
🇯🇵Nagaoka-shi, Japan
Investigational Site Number 392033
🇯🇵Okayama-shi, Japan
Investigational Site Number 392006
🇯🇵Osaka-shi, Japan
Investigational Site Number 392035
🇯🇵Sapporo-shi, Japan
Investigational Site Number 392046
🇯🇵Osaka-shi, Japan
Investigational Site Number 392001
🇯🇵Tenri-shi, Japan
Investigational Site Number 392015
🇯🇵Sagamihara-shi, Japan
Investigational Site Number 392019
🇯🇵Sakai-shi, Japan
Investigational Site Number 392040
🇯🇵Tsukuba-shi, Japan
Investigational Site Number 392032
🇯🇵Fujisawa-shi, Japan
Investigational Site Number 392026
🇯🇵Bunkyō-Ku, Japan
Investigational Site Number 392004
🇯🇵Fukui-shi, Japan
Investigational Site Number 392007
🇯🇵Fukuoka-shi, Japan
Investigational Site Number 392024
🇯🇵Izumisano-shi, Japan
Investigational Site Number 392002
🇯🇵Kumamoto-shi, Japan
Investigational Site Number 392011
🇯🇵Kumamoto-shi, Japan
Investigational Site Number 392010
🇯🇵Osaka-shi, Japan
Investigational Site Number 392045
🇯🇵Osaka-shi, Japan
Investigational Site Number 392021
🇯🇵Morioka-shi, Japan
Investigational Site Number 392005
🇯🇵Wakayama-shi, Japan
Investigational Site Number 392017
🇯🇵Nagakute-shi, Japan
Investigational Site Number 392025
🇯🇵Tsukuba-shi, Japan
Investigational Site Number 392043
🇯🇵Yokohama-shi, Japan
Investigational Site Number 392027
🇯🇵Yokohama-shi, Japan
Investigational Site Number 392048
🇯🇵Fukuoka-shi, Japan
Investigational Site Number 392016
🇯🇵Toyoake-shi, Japan
Investigational Site Number 392020
🇯🇵Kawaguchi-shi, Japan