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
WAKE-UP was a phase 3 randomized, double-blind, parallel-design trial evaluating MRI-based thrombolysis in patients with wake-up stroke.
| Feature | WAKE-UP |
|---|---|
| NCT ID | NCT01525290 |
| Title | Efficacy and Safety of MRI-based Thrombolysis in Wake-up Stroke |
| Condition | Stroke |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Primary purpose | Treatment |
| Lead sponsor | Universitätsklinikum Hamburg-Eppendorf |
2. Clinical Question
Population
Patients with stroke enrolled in a randomized clinical trial of MRI-based thrombolysis.
Intervention
Alteplase.
Comparator
Placebo.
Primary question
Does MRI-based thrombolysis with alteplase affect favourable outcome and safety outcomes at 90 days after stroke?
3. Trial Design
Participants were randomly assigned.
The trial used double masking.
A parallel-group design with two arms.
501 participants.
4. Endpoints
| Endpoint | Time frame | Description |
|---|---|---|
| Efficacy | 90 day after stroke | Favourable outcome (Modified Rankin Scale 0-1) |
| Safety | 90 day after stroke | Mortality; Death or dependency (Modified Rankin Scale 4-6) |
5. Planned Analysis
The ClinicalTrials.gov record identifies efficacy and safety endpoints but does not report posted statistical analyses or endpoint results.
The efficacy endpoint is a binary functional outcome based on the Modified Rankin Scale. A typical analysis for this type of endpoint compares the proportion of participants achieving a favourable outcome between randomized groups using an appropriate hypothesis test or regression model, with an effect estimate and confidence interval describing the magnitude and uncertainty of the difference.
The safety endpoint includes mortality and death or dependency outcomes. These outcomes are generally summarized by treatment group and compared using methods appropriate for binary clinical event data.
6. Statistical Methodology
Randomized comparison
Randomization creates the framework for comparing treatment groups because assignment, rather than clinical characteristics, determines the intervention received. Statistical comparisons are interpreted relative to the randomized groups.
Binary endpoint analysis
The primary efficacy endpoint is defined as favourable outcome on the Modified Rankin Scale. For binary outcomes, the analysis focuses on the difference between groups in the probability of achieving the prespecified outcome.
The confidence interval describes uncertainty around the estimated treatment difference.
Safety analysis
Safety outcomes require separate interpretation from efficacy because a treatment effect on functional outcome and a treatment effect on adverse clinical outcomes answer different questions.
7. Statistical Methods Explained
Why is randomization important?
Randomization helps balance known and unknown prognostic factors between treatment groups, supporting an unbiased comparison of outcomes.
Why analyze a Modified Rankin Scale outcome?
The Modified Rankin Scale measures disability and functional outcome after stroke. Defining a favourable outcome as Modified Rankin Scale 0-1 creates a clinically interpretable binary endpoint.
What does a confidence interval show?
A confidence interval describes statistical uncertainty around an estimated treatment effect. It does not describe the outcomes experienced by every individual patient.
Why are efficacy and safety analyzed separately?
Efficacy evaluates whether a treatment affects the intended clinical outcome, while safety evaluates important adverse outcomes. A single summary statistic cannot replace evaluation of both domains.
8. Limitations
- Posted results: The ClinicalTrials.gov record does not report statistical estimates, confidence intervals, or p-values for the listed endpoints.
- Endpoint interpretation: Functional outcomes after stroke depend on the definition and timing of assessment.
- Registry detail: The record does not report additional analysis details such as stratification, missing-data handling, interim analyses, or multiplicity procedures.
- Generalizability: Interpretation depends on the eligibility criteria and trial population represented in the registry.
9. Why This Trial Matters Statistically
WAKE-UP illustrates several important principles in clinical trial statistics:
| Concept | How it appears in WAKE-UP |
|---|---|
| Randomization | Randomized comparison of alteplase and placebo |
| Blinding | Double-masked design |
| Binary efficacy endpoint | Favourable outcome defined by Modified Rankin Scale 0-1 |
| Safety evaluation | Mortality and death or dependency outcomes |
| Clinical interpretation | Functional benefit and safety require separate assessment |
10. Sources
- ClinicalTrials.gov record: WAKE-UP (NCT01525290)
- PubMed: WAKE-UP publication record
- PubMed: Related publication record
- PubMed: Related publication record
- PubMed: Related publication record
- PubMed: Related publication record