On December 14, 1995, Centocor Inc announced that it was stopping the EPILOG trial (Evaluation of PTCA to Improve Long-term Outcome by c7E3 GP IIb/IIIa Receptor Blockade) because of positive findings at the first interim analysis of 1500 patients. As originally designed, the trial was to have included 4800 patients, both low risk and high risk, undergoing percutaneous intervention, randomized to a control arm: “standard”-dose heparin (100 U/kg bolus, titrated to an activated clotting time of ≥300 s) plus placebo, or to one of two experimental arms: standard-dose heparin plus the GP IIb/IIIa antibody c7E3 Fab (ReoPro 0.25 mg/kg bolus plus 0.125 μg · kg−1 · min−1 [up to a maximum of 10 μg/min] infusion for 12 hours), or “low”-dose heparin (70 U/kg bolus, to achieve an activated clotting time ≥200 s) plus c7E3 Fab. An interim analysis on the first 1500 patients enrolled in the trial was conducted in December of 1995, focusing specifically on the primary-outcome end points of death and myocardial infarction. Because efficacy of the experimental arms exceeded predetermined stopping levels (P<.0001), the Safety and Efficacy Monitoring Committee (SEMC) recommended that the study be stopped. The SEMC also noted that major bleeding events with c7E3 Fab were essentially the same as with placebo. Full data from all patients enrolled in the trial before it was stopped will be presented after complete adjudication of all end points, sometime in 1996.
On December 20, Centocor also announced that CAPTURE (Chimeric 7E3 Antiplatelet Therapy in Unstable Angina REfractory to Standard Treatment), an unstable angina trial using c7E3 Fab, also was stopped because of positive findings at an interim analysis. CAPTURE was originally designed as a placebo-controlled study of c7E3 Fab in 1400 patients with refractory unstable angina scheduled for PTCA and involved 75 clinical centers in Europe, Israel, and Canada. In the CAPTURE trial, patients were treated with a bolus (0.25 mg/kg) plus an infusion (10 μg/min) of c7E3 Fab, beginning 18 to 24 hours before PTCA, and continuing through 1 hour after PTCA. An interim analysis was conducted on data from the initial 1050 patients, and the results were recently reviewed by the study SEMC. Analysis focused on the primary composite clinical end point of the trial: the 30-day incidence of death, myocardial infarction, or need for urgent intervention. Efficacy was found to exceed a predetermined stopping level (P<.0072), and the SEMC recommended that the trial be stopped because of the positive results. Major bleeding rates were found to be acceptably low (1.7% for placebo, 2.9% for 7E3 Fab; P=NS), although somewhat higher than in EPILOG, perhaps because of higher heparin dosing or extended times of sheath placement. Review of the overall results of the trial will also be available sometime in 1996.
- Copyright © 1996 by American Heart Association