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Persistent Atrial Fibrillation Phase 4 Randomized NCT00845780

WISDOM: Complete Statistical Analysis of Amiodarone Withdrawal in Persistent Atrial Fibrillation

An independent statistical review of the randomized WISDOM trial evaluating withdrawal versus continuation of amiodarone therapy in successfully treated patients with persistent atrial fibrillation.

ClinicalTrials.gov record: NCT00845780 · Completed
Scope of this record

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

WISDOM was a randomized phase 4 parallel-group trial evaluating withdrawal versus continuation of amiodarone therapy in successfully treated patients with persistent atrial fibrillation.

37
Enrollment
2
Arms
2 years
Primary endpoint timeframe
4
Phase
FeatureWISDOM
ConditionPersistent Atrial Fibrillation
AllocationRandomized
Design modelParallel
MaskingNone
Primary purposeTreatment
Lead sponsorUniversity Medical Center Groningen
Study period2000-08 to 2009-06 primary completion

2. Clinical Question

Population

Successfully treated patients with persistent atrial fibrillation.

Intervention

Withdrawal of amiodarone therapy.

Comparator

Continuation of amiodarone therapy.

Primary question

Does withdrawal versus continuation of amiodarone affect the occurrence of late relapse of persistent atrial fibrillation over 2 years?

3. Trial Design

01
Enroll
37 patients
02
Randomize
Two groups
03
Assign
Withdrawal or continuation
04
Assess
2-year endpoint

4. Endpoints

EndpointDefinitionTime frame
Occurrence of late relapse of persistent atrial fibrillationRegistered primary endpoint2 years

5. Planned Analysis

The registry identifies the primary endpoint as the occurrence of late relapse of persistent atrial fibrillation over 2 years. No statistical analyses or numerical results were posted to ClinicalTrials.gov.

For a randomized comparison of time until relapse, a typical analysis would examine time-to-event outcomes using methods such as Kaplan-Meier estimation and comparisons between randomized groups using appropriate survival-analysis techniques. The choice of analysis depends on the prespecified statistical analysis plan, including definitions of relapse, censoring rules, and analysis populations.

6. Statistical Methodology

Randomization

Randomization creates treatment groups intended to be comparable at baseline. The purpose of the randomized comparison is to reduce bias from measured and unmeasured differences between groups.

Time-to-event analysis

Because the primary endpoint concerns occurrence of relapse over a defined follow-up period, the statistical framework commonly used for such outcomes accounts for both whether an event occurs and when it occurs.

Conceptual survival function
S(t) = Probability of remaining event-free beyond time t

Time-to-event methods allow participants with incomplete follow-up to contribute available information until censoring.

7. Statistical Methods Explained

Why does randomization matter?

Randomization supports an unbiased comparison of treatment strategies by assigning participants to groups without investigators selecting who receives each intervention.

Why analyze relapse over time rather than only relapse percentages?

Time-to-event methods incorporate when relapse occurs, not only whether relapse occurred by the end of follow-up.

What does censoring mean?

Censoring occurs when the event has not been observed for a participant during available follow-up. Statistical methods use the observed follow-up information without assuming the exact future outcome.

Why are confidence intervals important?

Confidence intervals describe uncertainty around an estimated treatment effect. They provide information about precision beyond a single point estimate.

8. Limitations

9. Why This Trial Matters Statistically

ConceptHow it appears in WISDOM
Randomized trial designParticipants were allocated randomly to two treatment strategies.
Parallel designTwo groups were compared concurrently.
Time-to-event endpointThe primary endpoint evaluates occurrence of relapse over 2 years.
Clinical endpoint definitionStatistical interpretation depends on the registry-defined relapse endpoint.

10. Important Interpretation Points

Statistical interpretation

A randomized comparison can estimate differences between treatment strategies, but the strength and precision of conclusions depend on the observed events, analysis method, and uncertainty around estimates.

Clinical interpretation

The primary endpoint focuses on late relapse of persistent atrial fibrillation. The registry record does not report outcome estimates or treatment-group comparisons.

11. Related Tutorials

12. Related Calculators

13. Sources