A UNMC researcher has determined that the investigational drug Eritoran used in a large clinical trial to treat a severe and often deadly infection known as sepsis did not reduce mortality. As a result of the study Eritoran will not be recommended for wider use and no further clinical trials are planned.
Eritoran would have been the first drug developed specifically to treat sepsis but, as a result of the study, it will not be recommended for use, said Andre Kalil, M.D., an associate professor of medicine at UNMC and principal investigator. The results of the study appeared in the March issue of The Journal of the American Medical Association.
Sepsis, which kills more than one million people a year in the United States, is brought on by any number of infections, such as pneumonia, urinary tract, abdominal or skin infections, and is usually treated by conventional antibiotics.
It is triggered by a component of bacteria called endotoxin that leads to the inflammatory response of the body’s immune system. In a five-year randomized trial at 200 hospitals worldwide, Dr. Kalil found that of the 1,961 patients treated with Eritoran only 72 percent survived.
Dr. Kalil and his collaborators were hoping for better results.
“Even with this powerful inhibitor we did not see improvement in survival,” Dr. Kalil said.
With conventional antibiotics the survival rate is 70 to 75 percent. The hope was that Eritoran would boost those numbers.
Eritoran was administered intravenously and works by grabbing onto the endotoxin that is a potent activator of the acute inflammatory response.
But that is just one pathway that triggers the sepsis, there are several others, Dr. Kalil said, and this might be why the drug was ineffective.
Another reason could be that the drug is not administered soon enough, he said.
“On average, once a patient was found to have developed sepsis, the drug was administered within nine hours of diagnosis, which was faster than previous studies,” he said.
Yet, that doesn’t account for the time lost before the patient presented at the hospital with the symptoms of infection that developed unknowingly throughout the body, Dr. Kalil said. Nor does it account for biological reasons why some people respond better to some drugs and others do not.
The study was conducted between 2006 and 2011 with support from Eisai Inc., the manufacturer of Eritoran. The drug company is not planning to pursue further studies, Dr. Kalil said.
Dr. Kalil is applying similar principles to another study looking at a different method for ridding the body of the bacteria that cause sepsis. Marius Florescu, M.D., an assistant professor in nephrology in the UNMC College of Medicine, is his co-investigator.
Using a device that acts like a filter, Drs. Kalil and Florescu hope to remove the endotoxin from the blood instead of just inhibiting it.
“As a clinician standing at the patient’s bedside, I am always wondering – what more can I do to help? It’s what keeps me going,” Dr. Kalil said.