Phase 3
N=18,144
IMPROVE-IT: Examining Outcomes in Subjects With Acute Coronary Syndrome: Vytorin (Ezetimibe/Simvastatin) vs Simvastatin (P04103)
Hypercholesterolemia · Myocardial Infarction
Bottom Line
View on ClinicalTrials.gov: NCT00202878 ↗Enrolled (actual)
18,144
Serious AEs
40.2%
Results posted
Sep 2015
Primary outcome: Primary: Time to First Occurrence of Cardiovascular Death, Major Coronary Event, or Non-fatal Stroke (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event) — 32.72; 34.67 Percentage of Participants — p=0.016
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- ezetimibe/simvastatin (Drug); simvastatin (Drug); Placebo for simvastatin 40 mg (Drug); Placebo for ezetimibe 10 mg/simvastatin 40 mg combination (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Organon and Co
- Primary completion
- Sep 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time to First Occurrence of Cardiovascular Death, Major Coronary Event, or Non-fatal Stroke (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event) |
32.72; 34.67 | 0.016 sig |
| SECONDARY Time to First Occurrence of Death From Any Cause, Major Coronary Event, or Non-fatal Stroke (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event) |
38.65; 40.25 | 0.035 sig |
| SECONDARY Time to First Occurrence of Coronary Heart Disease (CHD) Death, Non-fatal MI, or Urgent Coronary Revascularization With PCI or CABG ≥ 30 Days After Randomization (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event) |
17.52; 18.88 | 0.016 sig |
| SECONDARY Time to First Occurrence of CV Death, Nonfatal MI, UA With Hospitalization, All Revascularization Occurring ≥30 Days After Randomization, and Non-fatal Stroke (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event) |
34.49; 36.20 | 0.035 sig |
Summary
This is a randomized, active-control, double-blind study of subjects with stabilized high-risk acute coronary syndrome (ACS). The primary objective is to evaluate the clinical benefit of Ezetimibe/Simvastatin Combination 10/40 (single tablet, under the brand VYTORIN in the United States) compared with Simvastatin 40 mg. As per the original protocol, if low-density lipoprotein cholesterol (LDL-C) response was inadequate, the dose of simvastatin in the VYTORIN arm or simvastatin arm, could be increased to 80 mg (Note: per June 2011 protocol amendment, criteria for continued use of 80 mg simvastatin were modified and new increases of simvastatin dose to 80 mg were stopped). Clinical benefit will be defined as the reduction in the risk of the occurrence of the composite endpoint of cardiovascular (CV) death, major coronary events, and stroke.
Eligibility Criteria
Inclusion Criteria
- Clinically stable participants may be eligible to enroll within 10 days following hospital admission with high-risk acute coronary syndrome (either ST-elevation myocardial infarction [STEMI] or Non-STEMI or unstable angina)
- Participants not taking a statin must have an LDL-C of 125 mg/dl or less. Participants taking a statin must have an LDL-C of 100 mg/dl or less.
Exclusion Criteria
- Pregnant or lactating woman, or intending to become pregnant
- Participant with active liver disease or persistent unexplained serum transaminase elevation
- History of alcohol or drug abuse
- History of sensitivity to statin or ezetimibe
- A participant for whom discontinuation of existing lipid lowering regimen poses an unacceptable risk.
Data sourced from ClinicalTrials.gov (NCT00202878). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.