CINCINNATI--A nearly $30 million grant from the National Institutes of Health (NIH) will fund research led by the University of Cincinnati (UC) College of Medicine's Department of Emergency Medicine to examine the effectiveness of combination therapies implementing tissue plasminogen activator (tPA), a well-known clot-busting drug used to treat acute ischemic stroke.
The grant, the largest in the history of the UC Department of Emergency Medicine, will fund the enrollment of 1,200 patients across the United States, starting over the next 12 months. The study will be run through NIH StrokeNet, with plans for 110 hospitals to take part. StrokeNet, which is based at UC, is the national coordinating center for all stroke trials funded by the National Institute of Neurological Disorders and Stroke.
The research will look at whether combining tPA with either argatroban or eptifibatide, two types of blood thinners, will produce better results in stroke patients in the first 90 days post-stroke versus tPA with placebo.
The seeds for this project were planted in the early 2000s with UC research led by Art Pancioli, MD, Professor and Richard C. Levy Chair of Emergency Medicine, and Joseph Broderick, MD, professor in the Department of Neurology and Rehabilitation Medicine and director of the UC Gardner Neuroscience Institute. Their studies examined the combination of tPA and eptifibatide, which had previously been shown to be effective in treating heart attack victims. While their research established that the tPA/eptifibatide combination was safe in treating stroke patients, similar concurrent research at the University of Texas Health Science Center at Houston found that the combination of tPA and argatroban was also safe in treating stroke patients. When the two teams learned of each other's efforts, a partnership was formed to answer the question of whether the combination treatments improved the outcomes for stroke patients.
"One of the key elements of this is that it is a collaboration between institutions, and a collaboration between emergency medicine and neurology," says Opeolu Adeoye, MD, associate professor in the Department of Emergency Medicine, and the lead investigator in the study. "I believe this is the first phase III trial that is led by an emergency physician in stroke, and it's a culmination of a lot of people's work and collaboration across specialties and institutions, including within the College of Medicine."
Adeoye says when a stroke patient comes into the hospital, the goal is to get them treated as quickly as possible with IV tPA. Once that treatment is started, a discussion is held with the patient and/or the patient's family about taking part in the study. When consent is given, a three-sided coin will be flipped to see which combination of tPA therapy will be administered to the patient. They will either receive tPA with placebo, argatroban or eptifibatide, with the goal of starting the study drug within an hour of the beginning of the IV tPA treatment. Eligible patients can also undergo thrombectomy by a catheter device after starting the combination therapy.
The primary end-point for the research will be at 90 days, according to Adeoye.
"At 90 days after a patient has a stroke, we will interview them in person and see how they are doing," he says. "That's a standard timeline for seeing how stroke patients do after they are treated and released from the hospital. Stroke patients continue to improve over time, but the bulk of the gains that people get back after treatment for stroke happens in those first 90 days."
The NIH award is for five years, which will include a start-up and a wind-down period on both ends of the study. Considering the scope of the project, with 1200 patients at 110 locations, the research is labor intensive. In addition to establishing contracts with all of the hospitals and the agencies providing the drugs, drugs have to be purchased and individual follow-ups need to be done for each patient.
In the eyes of Adeoye, this will be money well spent.
"This is the dream. This is a unique opportunity that few researchers get," says Adeoye. "We have the opportunity to propose to definitively answer a question that could change how we treat a disease."