Dr. James Grotta
Dr. James Grotta

The 1995 paper announcing results of the first major trial showing benefits of a then-new clot-busting drug as a treatment for stroke has been voted one of the top nine papers in the 200-year history of the New England Journal of Medicine (NEJM). Two professors at The University of Texas Health Science Center at Houston (UTHealth) were involved in the groundbreaking research, which took place at Memorial Hermann-Texas Medical Center.

The paper, Tissue Plasminogen Activator for Acute Ischemic Stroke, published in the December 14, 1995 issue, revealed the first promising treatment for stroke and eventually changed stroke management.

Administered within three hours of the onset of stroke symptoms, tissue plasminogen activator (tPA) is a clot-dissolving agent that can reduce the effects of stroke and permanent disability.

Dr. James Grotta, chair of the Department of Neurology and the Roy M. & Phyllis Gough Huffington Distinguished Professor of Neurology, was principal investigator of the Houston clinical site, one of six sites that enrolled patients into the trial.

“At the time we were doing this study, there was no existing treatment for stroke patients,” Grotta said. “I think we were aware of the potential significance of our research for a number of reasons – the treatment we were testing (tPA) and the time frame we were treating patients in (90-190 minutes after the stroke) was truly ‘over the top’ in terms of being far more aggressive than anything done before, and we had a great group of gung ho investigators and leadership. But given past disappointments, it was still a surprise when we first saw the positive results. Once we saw the results, however, we knew it was important and would have a big impact.”

Dr. Barbara Tilley, professor and division director at The University of Texas School of Public Health, was principal investigator of the Coordinating Center for The National Institute of Neurological Disorders and Stroke t-PA Stroke Study Group. At the time of the study, she was on the faculty at Henry Ford Health Sciences Center in Detroit and helped design, manage, and analyze data for the trial.

“t-PA is the only treatment to date shown to be effective in reducing the effects of stroke for those who have stroke caused by a blood clot in the brain – an ischemic stroke,” Tilley said. “The longer the time to treatment in stroke cases, the lower the effect of the treatment.”

Tilley said that the outstanding Emergency Medical System (EMS) and hospital triage that Grotta helped organize for the original t-PA trial still helps patients who have a stroke today get to treatment quickly and increase their chance of a good recovery.

The results of this study completely changed how stroke patients were treated. Everyone from emergency personnel in the field to emergency room workers to physicians were retrained in the correct protocols, saving millions of lives.

UTHealth researchers continue to push the boundaries of stroke treatment. Grotta said the battle to reduce stroke is won or lost in the first hour after the onset of symptoms.

“We need to develop new treatments that build on tPA, and develop systems to get these treatments to patients faster,” Grotta said. “The other revolution in stroke treatment is to learn how to stimulate the brain’s intrinsic recovery process.”

That revolutionary work includes research led by Dr. Sean Savitz, associate professor of neurology and director of the Medical School’s Vascular Neurology Program, whose team is testing stem cell therapies to see if they can assist the brain in recovering from stroke.

Readers also voted the paper the most important study that the journal published in the 1990s.

-Shon Bower, School of Public Health, and Debra Mann Lake, Office of Advancement