–The results of TRUE-AHF won’t be presented at the ESC.
The results of a highly anticipated and already-delayed clinical trial won’t be presented until November at the American Heart Association meeting in New Orleans. Presentation of the trial was originally scheduled earlier his year as a late-breaking presentation at the American College of Cardiology meeting in March. When the ACC presentation was cancelled many assumed that the trial would be presented at the European Society of Cardiology meeting, which begins this weekend in Rome.
Now the study chairman, Milton Packer (Baylor University), has informed me that he will not be presenting the trial until November. Packer offered a detailed explanation for the delay and emphasized that when he does present the results he will be 100% confident in their validity. The trial, TRUE-AHF, is a phase 3 multicenter, randomized, double-blind, placebo-controlled trial designed to assess the efficacy and safety of the addition of an early infusion of the natriuretic peptide ularitide in addition to conventional therapy in 2,100 patients with acute decompensated heart failure. The trial is sponsored by the manufacturer of ularitide, Cardiorentis.
Packer said that the trial’s problems first emerged right before the trial was scheduled to be unblinded only days before the ACC. The executive committee was surprised by a serious problem with the trial data involving the apparent last minute appearance of more than 40 new endpoint events. “We went ballistic, the entire executive committee was concerned,” Packer told me. To ensure the integrity of the trial the executive committee decided to cancel the scheduled presentation. In order to get to the bottom of the problem they requested that Janet Wittes, an eminent statistician and clinical trial expert, perform a detailed forensic examination of the trial data.
Packer described Wittes’ role as performing “an independent third-party source verification of the raw database.” This, Packer said, represents an “unprecedented” degree of due diligence. “When I present this in November it will be based on a 100% validated database which has been through every quality test imaginable… my level of certainty will be higher than for any other trial,” Packer told me.
According to Packer, Wittes’ audit will be completed in September. It is possible, therefore, that Cardiorentis will release top line results of the trial before the full presentation by Packer at the AHA in November.
Packer also talked about his continued belief in the importance of the trial. “TRUE-AHF aims to build on the growing body of evidence to treat patients suffering from acute decompensated heart failure as early as possible, and will encourage heart failure experts, cardiologists and emergency physicians to work hand-in-hand to ensure an early enrolment of patients within the first hours after presentation to the hospital.” He compared TRUE-AHF to the early trials demonstrating the benefits of early treatment for patient with acute coronary syndromes. “We’re testing the hypothesis that when a person comes in with ADHF you have to put them on a vasodilator drip as soon as possible in order to make the cardiac pressure go down and reduce ischemic injury, and if you do that you save myocardium and prevent further myocardial damage, and that will have favorable effects on morbidity and mortality in the long term,” Packer explained.