title: Would tirofiban have been shown non-inferior to abciximab had the TENACITY trial not been terminated for financial reasons?
abstract: OBJECTIVE
  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: Geisinger Clinic, Danville, Pennsylvania, USA. pbberger@geisinger.edu
authors: Peter B
authors: PB
authors: Berger
authors: Judson B
authors: JB
authors: Williams
authors: Vic
authors: V
authors: Hasselblad
authors: Karen
authors: K
authors: Chiswell
authors: Karen S
authors: KS
authors: Pieper
authors: Robert M
authors: RM
authors: Califf
mesh_terms: D000077284:Abciximab; D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D057239:Early Termination of Clinical Trials / Q000191:economics*; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000209:etiology*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015607:Stents / Q000009:adverse effects*; D015996:Survival Rate; D000077466:Tirofiban; D016896:Treatment Outcome; D014443:Tyrosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D014443:Tyrosine; D000077466:Tirofiban; D000077284:Abciximab
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