|i found this from avii today discontinuing a possibly competitive cardiac program but i doubt its moving crdc..|
Following a futility analysis and data review, the Company decided to discontinue its clinical trial to assess the safety and efficacy of AVI-5126 in reducing clinically-significant graft failure in coronary artery by-pass grafting (CABG).
AVI initiated this study in April 2007 as a randomized, double-blind, placebo-controlled, multi-site adaptive design that was intended to enroll up to a total of 600 patients undergoing CABG. The goal of the study was to evaluate the safety and efficacy of exposing a patient's saphenous vein to AVI-5126 prior to grafting, compared to a placebo group treated with saline (1:1 randomization). The primary endpoint of the study was demonstration of greater than or equal to 50% reduction in the clinical graft failure rate (i.e., < 75% reduction in study vessel patency in all study vessels of a patient) in the AVI-5126 group compared to placebo at 1-year, based on angiography. An independent Data Safety Management Board (DSMB) reviewed available safety and efficacy data for each patient from the time of CABG until the end of study surveillance at 1-year in an unblinded fashion. After the first 47 patients were treated and assessed, the DSMB reported a higher than expected rate of graft failure based on 4-D CAT scans of coronary arteries at 1-Month and 3-Months after CABG.
Complete data from 45 subjects were available for analysis. Based on 4-D CAT scan results at Month 3, there were 13 patients with at least one graft failure out of 23 patients exposed to AVI-5126 and 7 patients with at least one graft failure out of 22 patients exposed to placebo (i.e., 57% failure rate for experimental versus 32% in control group). Therefore, the conditional power to meet the study's efficacy endpoint was only 66%. For 10 patients, angiograms were available at 1 year, and those confirmed the occlusions that were found by 4-D CAT scans at 3 months. Both 4-D CAT scans and angiography showed the same rate of re-occlusion in these patients. The probability of successfully attaining the study's clinical endpoint, even at this early stage, was deemed to be too low to warrant continuing the trial.
The analysis was not focused on clinical safety concerns since there was no significant difference between the AVI-5126 or placebo groups with respect to Major Cardiac Adverse Events (MACE). MACE is conventionally defined to include: cardiac death, myocardial infarction, emerging need for repeat CABG, stroke, major bleeding complications and organ failure....