Sepsis kills 250,000 Americans annually yet there is no FDA approved treatment; three drugs recently removed from market or failed clinical studies
Cooper University Hospital is the flagship investigative center for EUPHRATES, a pivotal North American multicenter clinical study that is testing whether a combination therapeutic/diagnostic (theranostic) can improve the survival of patients who suffer from septic shock. The study, in the process of expanding from 15 to 30 sites in the Unites States and Canada, is the first to evaluate a theranostic for the diagnosis and treatment of septic shock and is further distinguished by applying principles of personalized medicine to identify and treat a specific segment of the patient population that is at highest risk of death.
The statistics associated with sepsis are sobering. In the United States alone, sepsis affects more than 750,000 patients and claims more than 250,000 lives, which is more than colorectal, pancreatic and prostate cancer combined. Severe sepsis and septic shock, which are the most life-threatening stages of sepsis, have a combined mortality rate of 30-35 percent. The Global Sepsis Alliance has declared sepsis “a medical emergency beyond national borders and likely the leading cause of death worldwide, claiming tens of millions of lives every year.”
“Sepsis leading to septic shock is a healthcare crisis of pandemic scale in North America and around the world, yet there is not a single FDA-approved therapy for the condition, creating an urgent need for new effective and affordable treatments,” said Dr. Phillip Dellinger, Director of Critical Care Medicine and the Cooper Medical/Surgical Intensive Care Unit and principal investigator of the study at Cooper University Hospital. Dr. Dellinger is also Professor of Medicine at Cooper Medical School of Rowan University. “Current management of septic shock patients follows Surviving Sepsis Campaign guidelines based on early antibiotics, goal-directed resuscitation of the cardiovascular system and support of failing organs as needed. Previous efforts to develop effective treatments for sepsis have failed and a contributing factor might be that they were applied to a heterogeneous patient population. We are hopeful that a more targeted approach using characteristics of personalized medicine, such as in the EUPHRATES trial design, will lead to the identification of a targeted a group of patients most likely to benefit.”
The grim outlook for treatments worsened in late 2011 when the only approved therapy – Xigris – was taken off the U.S. market due to efficacy and safety problems. Earlier that year, another drug failed to demonstrate efficacy in its Phase III trial for severe sepsis. In February 2012, a late stage clinical study was halted due to safety concerns.
Previous clinical research has demonstrated that elevated levels of endotoxin in the blood (a condition known as endotoxemia) can act as a potent trigger of the “sepsis cascade,” the physiological chain of events that can quickly lead to organ failure and death. It is estimated that 50 percent of patients with septic shock – approximately 125,000 – suffer from endotoxemia. The theranostic being tested in the EUPHRATES study is comprised of the Endotoxin Activity Assay (EAA™), an FDA-cleared rapid diagnostic that measures endotoxin levels in the blood, and Toraymyxin, a therapeutic hemoperfusion device that removes endotoxin from the bloodstream. Although Toraymyxin is an investigational device in the U.S., it is approved in 18 countries and has safely treated more than 80,000 patients.
In 2009, a European Phase II multicenter, randomized, controlled clinical trial was terminated early on the basis of positive interim results which demonstrated that Toraymyxin reduced 28-day mortality in patients with severe sepsis and septic shock in comparison to those patients in the conventional therapy group (32 percent treated with Toraymyxin vs. 53 percent treated with conventional therapy).
About the EUPHRATES study:
Name: EUPHRATES: Evaluating Use of Polymyxin B Hemoperfusion in a Randomized controlled trial of Adults Treated for Endotoxemia and Septic Shock.
Stage: Phase III
Design: Randomized, double-blind, controlled comparing standard of care versus standard of care plus Toraymyxin, as directed by the EAA
Patient Population: Critically ill patients diagnosed with septic shock and elevated endotoxin levels as measured by the EAA
Targeted Enrollment: 360 patients
Number of locations: 30 centers in the U.S. and Canada (16 currently active)