Spectral Diagnostics, a Phase III company developing a theranostic treatment for patients with septic shock, has received FDA approval for an amended protocol for its EUPHRATES trial, which will now have two planned interim analyses instead of one.
Spectral requested the amendment, including the strategy for two interim analyses, primarily because the composite mortality rate (combined mortality rate for the treated and the placebo groups) for the EUPHRATES trial continues to track at a higher-than-predicted rate (approximately 35 per cent compared with a predicted rate of 27.5 per cent), resulting in a higher-than-anticipated event rate in the trial. The higher composite mortality rate suggests that patients who are most at risk and most likely to benefit from treatment are being randomised into the trial. A higher event rate gives greater statistical power to the trial.
EUPHRATES is a randomised, double-blind controlled, clinical trial that compares standard-of-care versus standard-of-care and Toraymyxin, directed by Spectral's EAA (Endotoxin Activity Assay). The latter is claimed to be the only FDA-cleared diagnostic for the risk of developing sepsis. The target population for EUPHRATES is critically ill patients with septic shock and endotoxemia (as measured by the EAA). The trial's primary endpoint is 28-day mortality. The study is currently targeted to enrol 306 evaluable patients at up to 60 North American sites. Contingent on maintaining current enrolment rates and timely site start ups, the trial should be fully enrolled by the end of 2014.
The first interim analysis will occur when 76 randomised patients have been followed for 28 days, at which point the DSMB will evaluate and report on the trial's ongoing safety. Based on the current rate of enrolment, results of that analysis are expected to be disclosed before the end of the first quarter of 2013. To date, 68 patients have been randomised into the trial after meeting both the clinical criteria and the biomarker criteria of a high endotoxin level.
The second interim analysis will occur after 184 randomised patients have been followed for 28 days. At the second analysis, the DSMB will advise Spectral on the trial's safety and efficacy. Stopping rules for efficacy and futility are included in the second interim analysis. A sample size recalculation will be done if necessary. Information from the second interim analysis is expected to be released in early-2014.