UC Awarded $4 Million to Look at Longer Treatment Window for Stroke

Since 2014, University of Cincinnati has been home to StrokeNet, the national coordinating center for all stroke trials within the National Institute of Neurological Disorders and Stroke (NINDS) network, which 

funds clinical trials and research studies to advance acute stroke treatment, stroke prevention and recovery and rehabilitation following a stroke. Spanning 25 regional stroke centers and nearly 300 participating hospitals, StrokeNet serves as the infrastructure and pipeline for new potential treatments for patients with stroke and those at risk for stroke.  

StrokeNet currently oversees this process for three trials funded by the National Institutes of Health. Most recently, UC was notified of a sub award for $4 million (with a renewing $1 million annually) to serve as both trial coordinator and a local recruiting center for an acute stroke interventional trial, known as the DEFUSE 3 trial, being led by Gregory Albers, MD, director of the Stanford Stroke Center. 

"StrokeNet's role is essentially managing the trials. We manage the clinical and administrative issues along with the principal investigators (PI)," says Joseph Broderick, MD, professor and director of the UC Gardner Neuroscience Institute and director of National Coordinating Center for NIH StrokeNet.

"We have a centralized Institutional Review Board (IRB) that does the vetting for all the centers in the country for coordinated stroke trials. All the resources for a trial for the patients come to StrokeNet, through us, to be distributed to the sites," Broderick says. 

Pooja Khatri, MD, professor in the Department of Neurology and Rehabilitation Medicine at UC College of Medicine, the StrokeNet co-director for acute stroke trials and director of the Cincinnati site in StrokeNet, says that the coordination of IRBs to one, "was no small task, but it was part of NIH's big effort to put pressure on researchers; they were pushing to make clinical trials run more efficiently. It used to be such a long process to start trials at each center."

In addition to centralizing the process and resources for trial efficiency, Khatri says, "We work closely with the person who proposed the research idea to design and implement the trial." 

"We can help develop the scope of the trial and roll it out successfully," she adds.

DEFUSE 3 is a multicenter randomized trial looking at treatment of acute stroke in patients who are beyond the standard timeframe for endovascular therapy, currently a recommended window of six hours since the patient was last known as being well or since the onset of symptoms. 

The DEFUSE 3 trial will work within a timeframe of six to 16 hours of treating patients exhibiting stroke symptoms, based on an imaging evaluation, using advanced MR or CT imaging as a criteria to select these patients eligible for trial consideration.

"Recent trials have demonstrated that endovascular therapy—a clot retrieval from an occluded blood vessel—is beneficial up to six hours in the appropriately selected patients. But what we don't know is, after that time window, if there would still be more benefit than harm in treating patients with stroke symptoms," says Achala Vagal, MD, associate professor in the Department of Radiology  at the UC College of Medicine. A neuroradiologist with the UC Gardner Neuroscience Institute, Vagal is also the local PI for the trial. 

The special brain imaging (perfusion studies) will show the size of the core of dead brain tissue and the additional brain area that is potentially salvageable. Vagal says, "The trial basically looks at this mismatch concept, if there is a small core tissue and a bigger salvageable amount of tissue. This is important criteria which can suggest that going in and removing the clot, even at this later time window, can still help the patients." 

Khatri says that more of the patients they see do arrive within the three hours of symptom onset, which could be due to better stroke awareness. "Of course, we want anyone with suspected symptoms of stroke to come to the ER as soon as possible, sooner is always better? but now, even in cases where several hours have passed, it's still important to come to the hospital. This trial could present an option," says Khatri.  

Vagal adds, "Unfortunately, there are those stroke patients who arrive at the ER beyond our current six hour time window. If this trial shows positive outcomes, it will really expand the use of endovascular treatment in these later time windows and help more patients achieve better outcomes." 

Khatri says there are 30 centers across the U.S. active in the trial so far, enrolling on average two patients a week. UC Medical Center is the location that serves as the trial site for Cincinnati and is a collaboration between radiologists and neurologists working with the UC Stroke Team. Patients arriving or transferred to UC are offered this trial if eligible.

StrokeNet hopes to hear about news of another trial in September. 

"All of our StrokeNet trials are on track with our projections. We are exactly where we should be with all of our trials, and it's kudos to the coordinating center team and our collaborators," says Khatri.