Objectives: To investigate whether tirofiban would have been non-inferior to abciximab had the trial completed enrollment and place the termination of this trial in a broader research ethics context.
Background: TENACITY was terminated by the sponsor for financial reasons. At the time, event rates for the 2 treatment arms were unknown.
Methods: TENACITY was designed to compare tirofiban with abciximab in approximately 8,000 patients; however, enrollment was terminated after 383 (4.8%) patients. The primary end-point was a composite of 30-day death, myocardial infarction, and urgent target vessel revascularization. Non-inferiority was defined as the likelihood that tirofiban would preserve at least 50% of the ability of abciximab to reduce the primary end-point at 30 days, based on abciximab's demonstrated ability to reduce such events by 43% (relative risk, 0.573; 95% confidence interval [CI], 0.507-0.648; P < 0.001). To determine the probability of non-inferiority given the patients already enrolled, a Bayesian approach was used.
Results: The primary composite end-point occurred in 8.8% of patients randomized to abciximab versus 6.9% receiving high-bolus-dose tirofiban (odds ratio, 0.77; 95% CI, 0.37-1.64). The estimated conditional power for the test that tirofiban would be non-inferior to abciximab if all patients been enrolled is 93.7%. Using the estimated predictive power method, the likelihood was 84.8%.
Conclusions: TENACITY was well powered to identify non-inferiority with tirofiban versus abciximab, and the patients enrolled strengthened the probability that this would have been the outcome had the trial been completed. When a clinical trial is terminated solely for financial reasons, it is incumbent upon the sponsor to provide proper patient follow-up and publication of the findings.
© 2013, Wiley Periodicals, Inc.