This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record.
1. Trial at a Glance
CLARITY-TIMI 28 was a randomized, parallel, quadruple-masked phase 3 trial evaluating clopidogrel (SR25990) versus placebo as adjunctive reperfusion therapy in acute coronary syndromes.
| Feature | CLARITY-TIMI 28 |
|---|---|
| ClinicalTrials.gov identifier | NCT00714961 |
| Status | COMPLETED |
| Primary completion date | 2005-01 |
| Lead sponsor | Sanofi |
| Sponsor type | INDUSTRY |
| Allocation | RANDOMIZED |
| Design model | PARALLEL |
| Masking | QUADRUPLE |
2. Clinical Question
Population
Patients with acute coronary syndromes.
Intervention
Clopidogrel (SR25990).
Comparator
Placebo.
Primary question
Does adjunctive clopidogrel improve the prespecified efficacy endpoint while maintaining acceptable safety compared with placebo?
3. Trial Design
Randomization
3491 participants
Treatment
Clopidogrel vs placebo
Assessment
Efficacy and safety endpoints
4. Endpoints
| Endpoint | Registry definition |
|---|---|
| Efficacy primary endpoint | Composite of an included infarct-related artery on the pre-discharge angiogram, or death or recurrent MI by the time of the start of coronary angiography. |
| Safety primary endpoint | TIMI major bleeding. |
5. Planned Analysis
The ClinicalTrials.gov record identifies the primary efficacy and safety endpoints but does not report posted statistical analyses or results.
For a composite efficacy endpoint involving clinical events and angiographic assessment, analyses would typically compare event occurrence between randomized groups using methods appropriate for binary outcomes and the prespecified analysis population. Safety endpoints such as TIMI major bleeding are typically summarized by treatment group and compared using prespecified safety analysis methods.
No formal statistical analyses were posted to ClinicalTrials.gov.
6. Statistical Methodology
Randomization
Randomization is the foundation of the treatment comparison. By assigning participants to treatment groups, randomized trials aim to balance measured and unmeasured baseline factors between groups.
Composite endpoints
The efficacy endpoint combines multiple clinical outcomes into one measure. Composite endpoints can increase statistical efficiency by accumulating events, but interpretation depends on the contribution and clinical importance of each component.
Safety endpoints
Safety outcomes are interpreted separately from efficacy. A treatment effect on the primary efficacy endpoint does not automatically describe the balance of risks and benefits.
7. Statistical Methods Explained
Why use a composite endpoint?
A composite endpoint can capture several clinically relevant outcomes together. The interpretation depends on which components occur and whether treatment effects are consistent across components.
Why is randomization important?
Randomization reduces systematic differences between treatment groups, allowing differences in outcomes to be attributed more reliably to the assigned intervention.
Why analyze safety separately?
Efficacy and safety answer different statistical questions. A safety endpoint evaluates adverse outcomes rather than treatment benefit.
What is a clinically meaningful endpoint?
Clinical trial endpoints should represent outcomes relevant to patients and investigators. Statistical significance alone does not determine clinical importance.
8. Limitations
- The registry does not report posted statistical analyses or numerical trial results.
- The composite efficacy endpoint contains multiple outcome types that may have different clinical interpretations.
- Without posted analyses, the statistical estimates, uncertainty measures, and treatment comparisons cannot be summarized from the registry record.
9. Why This Trial Matters Statistically
| Concept | How it appears in CLARITY-TIMI 28 |
|---|---|
| Randomized design | Two-arm randomized comparison. |
| Blinding | Quadruple masking. |
| Composite endpoint | Primary efficacy endpoint combines angiographic and clinical outcomes. |
| Safety analysis | TIMI major bleeding assessed as a primary safety endpoint. |
10. Sources
- ClinicalTrials.gov record: NCT00714961