Interim data found adding PHP/Hemoximer to vasopressor therapy increased number of deaths.
A Phase III trial evaluating Curacyte’s Nitric Oxide (NO) scavenger pyridoxalated hemoglobin polyoxyethylene conjugate (PHP), Hemoximer, in patients with catecholamine-resistant distributive shock has been terminated on futility grounds. The Phoenix study was designed to compare the effectiveness of continuous infusion using PHP/Hemoximer plus conventional vasopressor therapy with placebo plus conventional vasopressor therapy in over 450 patients. Primary and secondary endpoints were survival benefits after 28 days, and after 60 and 90 days, respectively.
Discontinuation of the study, on the recommendation of the trial’s data monitoring board, follows a review of data from 300 patients, which showed that the addition of PHP/Hemoximer to vasopressor therapy actually increased the number of deaths compared with placebo.
Curacyte called early termination of the trial “extremely disappointing and also surprising,” but says final analysis of data from the 377 enrolled patients will be used to determine the value of its NO-scavenging approach. “In any event, the analysis will provide helpful rationale for designing further studies in patients suffering from distributive shock,” states Ulrich Delvos, Ph.D., Curacyte CEO. The firm expects to present final data at the ISICEM meeting in Brussels in March 2012.
PHP is a modified hemoglobin product originally developed at Curacyte’s U.S. subsidiary, Apex Bioscience, to exploit the natural NO-scavenging and metabolizing properties of hemoglobin. A successfully completed Phase II study demonstrated that PHP could reverse vasodilation and resolve hypotension associated with distributive shock. At the end of March a second interim analysis of safety and mortality data from 50% of the study population led the data monitoring committee to recommend continuing the trial.