Lilly and Daiichi Sankyo Pull The Trigger and Kill Prasugrel Study Reply

Daiichi Sankyo and  Lilly said today that they had discontinued the TRIGGER-PCI (Testing Platelet Reactivity in Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy with Prasugrel) study  due to a lower than anticipated rate of primary endpoints (MI or cardiovascular death) in patients enrolled in the study. Taken in combination with the publication earlier this week of the negative GRAVITAS trial, the news, as noted on TCTMD, represents “another potential blow to the emerging field of personalized antiplatelet therapy.”

TRIGGER-PCI had planned to randomize 2150 patients with stable coronary artery disease with high platelet reactivity after DES implantation. The trial was discontinued after 18 months when a blinded review of the data found “a very high probability that the number of primary endpoints in the TRIGGER-PCI study would be insufficient for clinically relevant statistical analyses.”

“We were surprised to find an extremely low number of heart attacks and cardiovascular deaths in the patients included so far,” said the trial PI, Franz-Josef Neumann, in a press release issued by the sponsors. “With such a low number of events, it appeared highly unlikely to demonstrate a statistically significant and clinically relevant benefit of improved antiplatelet therapy in stable CAD patients with successful elective PCI.”

A Lilly senior medical director  emphasized that “the study was not stopped for lack of efficacy or safety reasons.”

In a Heartwire report, Neumann said that previous studies with the VerifyNow test, used in both the GRAVITAS and TRIGGER-PCI studies, probably “somewhat overestimated the impact of platelet function tests on patient outcome. We have to rethink the concept of platelet function testing. . . . For the moment, it’s clear we have no therapeutic impact of testing.”

Here is the statement from Daiichi Sankyo and Eli Lilly:

Discontinuation of TRIGGER-PCI Study

Media Statement

Daiichi Sankyo, Inc. and Eli Lilly and Company announced today the decision to discontinue the “Testing Platelet Reactivity in Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy with Prasugrel (TRIGGER-PCI)” study due to a low rate of primary cardiovascular events (heart attacks and cardiovascular deaths) in the patient population enrolled in the study.

The TRIGGER-PCI study was designed to compare the efficacy and safety of prasugrel (10 mg/day) versus clopidogrel (75 mg/day) for the reduction of adverse cardiovascular outcomes in patients with stable coronary artery disease (CAD) and high platelet reactivity on clopidogrel after successful implantation of coronary drug-eluting stents. The study excluded patients for whom Effient is currently indicated, those with acute coronary syndrome (ACS) who are managed with percutaneous coronary intervention (PCI) with or without stent placement.

To date, after approximately 18 months since the trial enrollment began, very few cardiovascular events (heart attacks and cardiovascular deaths) have occurred in the study. The sponsors along with the TRIGGER-PCI study Steering Committee and primary investigator, Franz-Josef Neumann, MD, managing medical director, Heart Centre Bad Krozingen, Germany, determined after a blinded review of study data that there is a very high probability that the number of primary endpoints in the TRIGGER-PCI study would be insufficient for clinically relevant statistical analyses.

The occurrence of fewer than anticipated cardiovascular events (heart attacks and cardiovascular deaths) is likely due to the studied population (low-risk, stable CAD patients after successful, uncomplicated PCI).

“We were surprised to find an extremely low number of heart attacks and cardiovascular deaths in the patients included so far,” said Dr. Neumann. “With such a low number of events, it appeared highly unlikely to demonstrate a statistically significant and clinically relevant benefit of improved antiplatelet therapy in stable CAD patients with successful elective PCI.”

“Since originally designing the TRIGGER-PCI study, we’ve determined from results of other trials and the pooled TRIGGER-PCI results that event rates are too low for clinically relevant statistical analysis. Thus, continuing the study would not have allowed us to show improved clinical outcomes in this patient population,” said Gregg W. Stone, MD, Director of Cardiovascular Research and Education Center for Interventional Vascular Therapy New York-Presbyterian Hospital and U.S. TRIGGER-PCI lead study investigator.

“We are absolutely committed to further evaluating Effient in clinical trials and have a rigorous clinical trial program in patients with ACS underway. We would like to extend our deep appreciation to the study investigators and the patients who enrolled in TRIGGER-PCI,” said Jeff Riesmeyer, MD, senior medical director, Cardiovascular, Eli Lilly and Company. “It’s important to note that the study was not stopped for lack of efficacy or safety reasons. The decision to discontinue this study should not impact prescribing of Effient for appropriate patients with ACS managed with PCI.” Page 2 of 3

Effient is approved by the U.S. Food and Drug Administration and the European Commission to reduce the risk of future heart-related events, such as heart attack or stent thrombosis, in patients with acute coronary syndromes (ACS) who are treated with PCI.

Study participants with questions should contact their study teams for instructions and should not discontinue any study medications without first consulting with their study teams. Effient patients with questions should contact their healthcare providers or The Lilly Answers Center (TLAC) at 1-800-LillyRx (1-800-545-5979).

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