CHAMPION PHOENIX Data Support Intravenous Cangrelor

March 10, 2013—The Medicines Company (Parsippany, NJ) reported results from the CHAMPION PHOENIX phase 3 clinical trial comparing the company's intravenous antiplatelet cangrelor to oral clopidogrel in patients undergoing percutaneous coronary intervention (PCI). Cangrelor is an intravenous, small-molecule antiplatelet agent that is in development to prevent platelet activation and aggregation leading to thrombosis in the acute care setting, including in patients undergoing PCI.

The CHAMPION PHOENIX trial is a double-blind, parallel group, randomized study composed of 11,145 patients that compares cangrelor to a clopidogrel loading dose administered as soon as possible after it is determined that the patient will undergo PCI.

The trial's coprincipal investigators are Deepak L. Bhatt, MD, and Robert A. Harrington, MD. Dr. Bhatt presented the results at the American College of Cardiology's 62nd annual scientific session in San Francisco. The results were concurrently published online ahead of print in The New England Journal of Medicine.

According to the company's press release, the CHAMPION PHOENIX results showed that patients treated with cangrelor had a 22% reduction in odds of experiencing the primary endpoint, which was a composite incidence of death, myocardial infarction (MI), ischemia-driven revascularization (IDR), or stent thrombosis (ST) at 48 hours after randomization. Cangrelor also showed a 38% odds reduction of the key secondary endpoint (incidence of stent thrombosis at 48 hours).

Detailed findings were outlined in the press release.

In a modified intention-to-treat population, 5,472 patients were randomized to cangrelor and 5,470 patients were randomized to clopidogrel. For cangrelor versus clopidogrel at 48 hours, the primary endpoint of death, MI, IDR, and ST was 4.7% versus 5.9%, an odds reduction of 22% (P = .005). The key secondary endpoint of ST was .8% versus 1.4%, an odds reduction of 38% (P = .01); for MI, 3.8% versus 4.7%, an odds reduction of 20% (P = .02); for Q-wave MI, .2% versus .3%, a 39% odds reduction (P = .19); for IDR, .5% versus .7%, a 26% odds reduction (P = .22); for death, .3% versus .3%, no odds reduction (P > .999); and for death or ST, 1.1% versus 1.6%, a 33% odds reduction (P = .02).

The incidence of the primary endpoint in selected subgroups was reported as follows: for a clopidogrel loading dose of 300 mg (n = 2806), it was 5.8% versus 6.8%, a 16% odds reduction (P = .27); for a clopidogrel loading dose of 600 mg (n = 8133), it was 4.3% versus 5.6%, a 23% odds reduction (P = .009); for the timing of the loading dose before PCI (n = 6902), it was 4.8% versus 6%, a 20% odds reduction (P = .033); and for timing of the loading dose after PCI (n = 3976), it was 4.3% versus 5.4%, a 21% odds reduction (P = .12).

In its press release, The Medicines Company noted that the findings were consistent across all analyzed subgroups of patients, including age, geography, diagnosis at presentation, and the choice of periprocedural anticoagulant. At 30 days, the rate of the composite primary efficacy endpoint remained significantly lower in the cangrelor group than in the clopidogrel group, and the relative reduction in stent thrombosis also persisted.

Additionally, the primary safety endpoint of severe bleeding at 48 hours not related to coronary artery bypass grafting was measured according to the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) criteria. Several other bleeding definitions were also applied. More sensitive measures did show an increase in bleeding with cangrelor, but there was no significant difference in the rate of transfusions.

In a safety population of 5,529 for cangrelor and 5,527 for clopidogrel, bleeding was measured by GUSTO, TIMI, and ACUITY definitions.

By GUSTO criteria, for cangrelor versus clopidogrel, the rates of severe bleeding were .2% versus .1% (odds ratio [OR], 1.5; 95% confidence interval [CI], 0.53–4.22). The rates of moderate bleeding were .4% versus .2% (OR, 1.69; 95% CI, .0.85–3.37).

By TIMI definition, the rates of major bleeding for cangrelor versus clopidogrel were .1% versus .1% (OR, 1.0; 95% CI, 0.29–3.45). Rates of minor bleeding were .2% versus .1% (OR, 3.0; 95% CI, .81–11.1). And, major or minor bleeding rates were .3% versus .1% (OR, 1.75; 95% CI, .73–4.18).

By ACUITY criteria, major bleeding rates were 4.3% versus 2.5% (OR, 1.72; 95% CI, 1.39–2.13) and rates of major bleeding without hematoma were .8% versus .5% (OR, 1.62; 95% CI, .99–2.64).

The rates for any blood transfusion were .5% for cangrelor versus .3% for clopidogrel (OR, 1.56; 95% CI, 0.83-2.93).

The primary efficacy and primary safety endpoints were combined to provide a composite endpoint of net adverse clinical events in the modified intention-to-treat population. The rate of net adverse clinical events of death, MI, IDR, ST, or GUSTO-defined severe bleeding was 4.8% for cangrelor versus 6% for clopidogrel (OR, .8; 95% CI, .67–.94; P = .008).

The rate of adverse events related to treatment was similar in the cangrelor and clopidogrel groups (20.2% and 19.1%, respectively; P = 0.13). There were significantly more cases of transient dyspnea with cangrelor than with clopidogrel (1.2% vs 0.3%; P < .001), a finding that was also observed in the previous CHAMPION studies.

In 2011, the company reported results of the BRIDGE trial, a prospective, randomized, double-blind, placebo-controlled multicenter trial that evaluated cangrelor or placebo in 210 patients with an acute coronary syndrome or treated with a coronary stent and receiving a thienopyridine awaiting coronary artery bypass graft surgery.

The company advised that cangrelor is an investigational agent not approved for commercial use in any market. The Medicines Company plans to submit cangrelor for market approvals in the United States and Europe, and anticipates that it will submit these data for a new drug application to the US Food and Drug Administration in the second quarter along with findings of previous studies, including the BRIDGE trial.