Researchers at the University of Kansas Medical Center are testing the boundaries of stroke care with their participation in two international clinical research trials that could lead to more treatment options for stroke patients and an expanded window of time to treat them effectively.

KU Medical Center is one of 99 sites worldwide for the TIMELESS study, funded by Genentech, looking at the effectiveness of treating patients with a clot-busting drug within 4.5 to 24 hours of the onset of stroke symptoms. Meanwhile, in the SELECT 2 study, KU Medical Center is one of 30 sites around the world testing the effectiveness of performing thrombectomies, the surgical removal of blood clots, in stroke patients with ASPECT scores between 3 and 5 and/or a core infarct size of greater than 50 cubic centimeters, both of which are a greater amount of tissue damage than previously thought treatable as shown on advanced perfusion imaging.

ASPECT scores are used to determine the level of tissue damage from stroke. The score is calculated using a CT scan and a perfusion scan, looking at 10 specific locations on each side of the brain, deducting one point for each dark spot visible on the scan, and the stroke size. Currently, the American Heart Association and American Stroke Association guidelines recommend treating patients with scores of 6 or higher.

"With these trials, we're covering the whole spectrum of stroke, not just the patients who fall within our current recommended standards of care," said Michael Abraham, M.D., associate professor of neurology at the KU Medical Center. "We can potentially treat patients in these trials we would not normally treat, possibly giving them a chance at much better outcomes."

Larger window of time for effective treatment

For more than 20 years, the first line of standard of care treatment for patients with acute stroke has been IV alteplase, an injectable drug that helps break up blood clots, within 4.5 hours of symptom onset. While treatment outside of that recommended time frame has been studied, none of the findings have been conclusive. The TIMELESS trial is seeking to change that by using a thrombolytic drug called tenecteplase to treat patients from 4.5 to 24 hours after the onset of symptoms.

Thrombolytics, which are used to treat emergency conditions such as ischemic stroke, heart attacks or massive pulmonary embolisms, currently are approved by the U.S. Food and Drug Administration for use up to within three hours of symptom onset, while standard of care guidelines support use up to 4.5 hours.

"TIMELESS is very innovative because potentially expanding the medical treatment window to 24 hours is crucial for those patients who have strokes in the middle of the night while they are sleeping, as well as those patients who live in areas where they must travel long distances to get to a center with capabilities to perform more specialized interventional treatments for stroke," said Sabreena Slavin, M.D., assistant professor of neurology at KU Medical Center and the site principal investigator for the TIMELESS study. "Similar to IV alteplase, IV tenecteplase can be given as an injectable by emergency departments in urban and rural centers prior to potential transfer to advanced care centers."

KU Medical Center is one of two TIMELESS study sites in Kansas and the only site in the state working in conjunction with an advanced comprehensive stroke center. The University of Kansas Health System was the fourth in the nation to earn that designation from the Joint Commission and the American Heart Association and American Stroke Association.

The 18-month study is expected to run through September 2020.

More treatment options

While the goal is always to restore stroke patients back to full health, that's not always possible, particularly when there is significant tissue damage. Yet researchers suspect, even in these severe cases, there still may be a chance to improve quality of life. Consider instances in which the subcortex of the brain is damaged by stroke, but the cortex, where speech and other higher order functions come from, is spared. Based on current guidelines, physicians are not always sure if treatment will help or hurt a patient. The SELECT 2 trial could help better answer that question.

"Maybe we can't make this person good, but we can make them better than if we didn't do anything. Better could be the difference if a person may not be able to speak, but they may be able to walk. Or, they may not be able to walk, but they can speak," said Abraham, the study's site primary investigator. "If you can't walk, that changes not just your life, but the lives of your spouse, children and caregivers where you would always need somebody. We may be able to improve that."

Performing thrombectomies on patients with low ASPECT scores could have an additional benefit of saving them from undergoing a hemicraniectomy, a surgery in which part of the skull is removed to allow the brain to swell outward. Without that relief, brain tissue inside the skull would swell inward onto normal tissue, causing death or herniation, the shifting of tissue from one space in the brain to another space in the brain.

The SELECT 2 study is anticipated to run through May 2021.

KU Medical Center also was one of eight sites nationally for the SELECT 1 trial, which looked at using perfusion imaging to assist in determining a stroke patient's eligibility for treatment.

Both TIMELESS and SELECT 2 will be conducted in acute care settings. Anyone who comes to the Emergency Department at The University of Kansas Health System or who is transferred to the health system with stroke symptoms may be eligible for participation in the studies with KU Medical Center if inclusion criteria are met.

"It is important to remember that these trials are being done to help us know which is better between treatment or current standard of care, so patients will get randomized to either treatment or standard of care," Abraham said.

For more information about the TIMELESS and SELECT 2 trials, visit clinicaltrials.gov.