The PHOENIX trial is a European, placebo-controlled, Phase III study treating patients in catecholamine-resistant, distributive shock with the Nitric Oxide (NO) scavenger PHP / Hemoximer.
The study was launched by Curacyte AG in Austria, Belgium, Germany, Spain, The Netherlands and in the United Kingdom in 2009. Today, the outcome of the third interim analysis on safety and mortality data of 300 patients, or 66% of the study population in the trial is reported. Statistical results were reviewed in an unblinded fashion by an independent Data Monitoring Board (DMB). The DMB, consisting of intensive care physicians, one bioethical expert and one statistician from the US and Europe came to the unanimous conclusion, that the study should be terminated.
The trial was designed to statistically prove survival benefit of patients treated with PHP after 28 days compared to placebo (+ standard care), and at day 60 and day 90 as secondary endpoints. After treatment of two thirds of the patient population the numerical number of deaths in the PHP / Hemoximer cohort exceeded that of the placebo group. Given the current status of the study there is no more chance that the study could demonstrate a statistically significant efficacy on 28-day all-cause mortality in favor of PHP / Hemoximer. Therefore, the continuation of the PHOENIX study with enrolment of new patients under the premise to detect an unlikely difference would be unethical. Based on the DMB’s recommendation Curacyte AG has suspended the PHOENIX trial with immediate effect.
Curacyte’s Chief Executive Officer, Dr. Ulrich Delvos comments: “Early termination of a trial for missing the endpoint, in particular, in this medically underserved patient population is extremely disappointing and also surprising for all our stakeholders. The final analysis of the 377 patients enrolled into the PHOENIX study will shed more light on the reasons. These results will finally determine the value of our NO-scavenging approach with PHP / Hemoximer in these patients. In any event, the analysis will provide helpful rationale for designing further studies in patients suffering from distributive shock. Presentation of the final data to the scientific community is planned for March 2012 at the occasion of the ISICEM Meeting in Brussels”.
About PHP / Hemoximer: Scientists from Apex Bioscience, Inc. (Chapel Hill, North Carolina), Curacyte’s wholly-owned US subsidiary, have developed the modified haemoglobin product with the intention to exploit the natural NO-scavenging and metabolizing properties of hemoglobin. Compelling evidence suggests that NO is the causative agent responsible for vasodilation and hypotension in distributive shock. In the successfully conducted Phase II clinical development program PHP has previously been demonstrated to reverse vasodilation and resolve hypotension associated with this shock form.
About the PHOENIX trial:
This Phase III, multi-center, randomized, placebo-controlled study compares the effectiveness of continuous infusion of PHP / Hemoximer plus conventional vasopressor therapy against placebo (normal saline) plus conventional vasopressor therapy in patients with catecholamine-resistant distributive shock. In addition, the safety and tolerability of this new treatment modality will be evaluated.
For inclusion into the trial the patients had to be adequately resuscitated with fluids and must require a norepinephrine dose of ≥0.3 mcg/kg/min to maintain a mean arterial blood pressure of ≥ 65 mmHg. Furthermore, patients had to fulfill at least two criteria indicative of a systemic inflammatory response (“SIRS” criteria). PHP / Hemoximer as active compound or placebo was administered by continuous intravenous infusion at 0.25 ml/kg/hr for a maximum of 150 hours.
Efficacy was to be demonstrated by PHP significantly reducing 28-day all-cause mortality. Secondary endpoints include: Survival time, survivor days in the intensive care unit (“ICU”) and time on mechanical ventilation and on vasopressors.
The trial was conducted in 72 hospitals in six European countries and was led by Prof. Jean-Louis Vincent from the Erasme University in Brussels as the coordinating principal investigator in Europe.
Curacyte AG is a biopharmaceutical company dedicated to the development of new therapeutics for acute and critical care. After sale of its preclincal technology platform for low molecular weight protease inhibitors to The Medicines Company in 2008, Curacyte has focussed its efforts on the development of PHP / Hemoximer.