March 10, 2013 – DCRI clinical events classification work leads to a new definition for myocardial infarction and more focused trial results.
Late-breaking results from the CHAMPION-PHOENIX trial reveal that cangrelor, an intravenous, potent, and reversible P2Y12 inhibitor, was found to significantly reduce the risk of acute ischemic cardiac events in patients being treated with percutaneous coronary intervention. This finding differs from results from this trial’s predecessors (CHAMPION-PCI and CHAMPION PLATFORM), and the success of CHAMPION-PHOENIX is in part due to the expertise of the DCRI’s clinical events classification (CEC) group, statistical group, and faculty leadership. The results were announced today at the American College of Cardiology 2013 Scientific Sessions in San Francisco, California.
CHAMPION-PHOENIX was a randomized, double-blind, double-dummy (meaning that patients have an equal probability of receiving either treatment, and that patients, clinicians, and researchers don’t know patients’ treatment assignments) trial comparing cangrelor with clopidogrel in approximately 10,900 patients. The primary endpoint was a composite of death, myocardial infarction (MI, or heart attack), ischemia-driven revascularization, or stent thrombosis.
Kenneth Mahaffey, MD, who co-chaired the trial’s CEC committee along with Sergio Leonardi, MD, explained that after experiencing some challenges in adjudicating early MI endpoints in CHAMPION-PCI and CHAMPION PLATFORM, trial researchers carefully redefined what was classified as an MI to more clearly distinguish between an enrolling event and an endpoint event. Mahaffey commented that because the enzyme markers that are used to define MI often stay elevated for a period of time after a heart attack, it can be difficult to differentiate between marker elevations that are due to either the original MI or another heart attack shortly thereafter.
“We went back and performed a series of analyses from the first two trials and identified mechanisms by which we could adjudicate MI events with revised MI definitions,” Mahaffey said. “We then applied the new procedures and definitions to potentially achieve more specificity in identifying MIs that occurred because of the procedure and not as a result of the patient’s original MI.”
According to Project Leader for CEC Operations Matthew Wilson, RN, the use of core laboratory data —angiographic evidence (TIMI flow, distal embolization, side branch closure) systematically across all patients to identify events for review, as well as define them in the adjudication effort, also differentiated CHAMPION-PHOENIX from previous phases. He commented that many trial team members felt that the universal MI definition updates that were announced at the 2012 European Society of Cardiology meeting in Munich validated their approach of collecting and using angiographic data.
“Utilizing systematic assessment and including angiographic evidence for determining an endpoint MI is becoming more popular in [acute coronary syndrome] trials,” said Wilson. “Therefore, angiographic complications as a component of the MI definition have become more specific as evidenced by the universal MI working group’s updates to the MI definition.”
Using this new approach to distinguishing between trial events, Mahaffey said the study results indicate that cangrelor was more effective in reducing acute ischemic events, including MI and stent thrombosis, without an increase in major bleeding. He commented that further review of CHAMPION-PHEONIX data will likely allow researchers to learn more about how to define MIs in patient populations with acute coronary syndromes undergoing percutaneous coronary intervention.
The trial team included:
Kenneth Mahaffey, MD Co-Chair
Sergio Leonardi, MD Co-Chair
Renato Lopes, MD CEC Committee Member
Pierluigi Tricoci, MD CEC Committee Member
Matthew Brennan, MD CEC Committee Member
Chiara Melloni, MD CEC Committee Member
Luciana Amaganijan, MD Phase 1 CEC Member
Pedro Barros, MD Phase 1 CEC Member
Akshay Bagai, MD Phase 1 CEC Member
Rob Harrison, MD Phase 1 CEC Member
Monique Anderson, MD Phase 1 CEC Member
Matt Wilson, RN Senior Project Leader
Stacey Mangum, RN Lead Clinical Trial Coordinator
Dimitrios Stournaras, MS Lead Clinical Data Specialist
Dianne Gallup, Lead Statistician
DCRI Data Management:
Curtis Campbell, Data Program Manager