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.
RCT Entities:
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.
Authors: Marco Valgimigli; Giuseppe Biondi-Zoccai; Matteo Tebaldi; Arnoud W J van't Hof; Gianluca Campo; Christian Hamm; Jurriën ten Berg; Leonardo Bolognese; Francesco Saia; Gian Battista Danzi; Carlo Briguori; Ertan Okmen; Spencer B King; David J Moliterno; Eric J Topol Journal: Eur Heart J Date: 2009-09-14 Impact factor: 29.983
Authors: G Viberti; G Slama; G Pozza; A Czyzyk; R W Bilous; A Gries; H Keen; J H Fuller; G Menzinger Journal: Lancet Date: 1997-07-19 Impact factor: 79.321
Authors: Henry R Black; William J Elliott; Gregory Grandits; Patricia Grambsch; Tracy Lucente; William B White; James D Neaton; Richard H Grimm; Lennart Hansson; Yves Lacourciere; James Muller; Peter Sleight; Michael A Weber; Gordon Williams; Janet Wittes; Alberto Zanchetti; Robert J Anders Journal: JAMA Date: 2003 Apr 23-30 Impact factor: 56.272
Authors: Marc Cohen; Gian Franco Gensini; Frans Maritz; Enrique P Gurfinkel; Kurt Huber; Ari Timerman; Maria Krzeminska-Pakula; Jose Santopinto; Carole Hecquet; Luc Vittori Journal: Circulation Date: 2003-10-21 Impact factor: 29.690
Authors: Nicolette M S K J Ernst; Harry Suryapranata; Kor Miedema; Robbert J Slingerland; Jan Paul Ottervanger; Jan C A Hoorntje; A T Marcel Gosselink; Jan-Henk E Dambrink; Menko-Jan de Boer; Felix Zijlstra; Arnoud W J van 't Hof Journal: J Am Coll Cardiol Date: 2004-09-15 Impact factor: 24.094