A randomized, double-blind, active-controlled phase 2 trial to evaluate a novel selective and reversible intravenous and oral P2Y12 inhibitor elinogrel versus clopidogrel in patients undergoing nonurgent percutaneous coronary intervention: the INNOVATE-PCI trial.

BACKGROUND We evaluated the safety, efficacy, and tolerability of elinogrel, a competitive, reversible intravenous and oral P2Y(12) inhibitor that does not require metabolic activation, in patients undergoing nonurgent percutaneous coronary intervention. METHODS AND RESULTS In a randomized, double-blind, dose-ranging phase 2b trial, 652 patients received either 300 or 600 mg of clopidogrel pre-percutaneous coronary intervention followed by 75 mg daily or 80 or 120 mg of IV elinogrel followed by 50, 100, or 150 mg oral elinogrel twice daily. Numerous exploratory safety and efficacy end points were assessed and, as such, had no prespecified primary end point, and the study was not powered to conclusively evaluate its objectives. Thrombolysis in myocardial infarction combined bleeding was increased with elinogrel (hazard ratio, 1.98; 95% confidence interval, 1.10 to 3.57), related largely to increased bleeding requiring medical attention (elinogrel 47/408 [11.5%] versus clopidogrel 13/208 [6.3%]) and occurring primarily at the percutaneous coronary intervention access site. Efficacy end points and postprocedure cardiac enzyme were similar, but there was a nonsignificant higher frequency of periprocedural myocardial infarctions in the elinogrel arms (OR, 1.59; 95% confidence interval, 0.79 to 3.48). There was an increased incidence of dyspnea (elinogrel 50/408 [12.3%] versus clopidogrel 8/208 [3.8%]) and transaminase elevation (alanine transferase/aspartate transferase >3× the upper limit of normal; elinogrel 18/408 [4.4%] versus clopidogrel 2/208 [1.0%]) in the elinogrel arms, but there were no cases of heart block, bradycardia, hypotension, or liver failure. CONCLUSIONS In patients undergoing nonurgent percutaneous coronary intervention and in comparison with clopidogrel, intravenous and oral elinogrel therapy did not significantly increase thrombolysis in myocardial infarction major or minor bleeding, although bleeding requiring medical attention was more common. The significance of these findings will need to be more definitively determined in future Phase 3 studies. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00751231.