Manitoba stroke trial tests clot-busting drugs for patients on blood thinners

A Winnipeg neurologist is leading a major international trial to determine if stroke patients who are on strong blood thinners can safely receive clot-busting drugs, a treatment currently denied to them. The study could open up new options for a significant and growing group of patients. Dr. Nishita Singh, a stroke neurologist and clinician scientist at Health Sciences Centre Winnipeg, is the principal investigator for the Canadian arm of the trial. The research, known as the DOSE trial, is part of the ACT-GLOBAL platform trial coordinated by the University of Calgary and the George Institute.

Approximately seven people suffer a stroke every day in Manitoba, or about 2,000 per year, according to Shared Health. Stroke is the third leading cause of death in Canada and a leading cause of disability. For patients who arrive at an emergency department within 4.5 hours of symptom onset, the standard treatment is a thrombolytic medication to dissolve the clot. "We keep saying that time is brain," said Singh. "If you treat patients within that four-and-a-half-hour window...we can get them those clot busting medications, which can potentially reverse their symptoms."

However, current practice excludes patients who are already on strong blood thinners, such as those for heart conditions, from receiving this therapy. "People who are on strong blood thinners are typically excluded from getting this medication," said Singh. "That’s because people think that because someone’s already on a strong blood thinner, if you give another strong blood thinner, you may increase risk of internal or external bleeding." She notes this group is not small and is growing steadily, representing about one in five stroke patients. "For these patients who come in, we really can’t offer them anything to resolve their symptoms."

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The DOSE trial is investigating whether providing a low dose or a standard dose of thrombolytics to these patients results in better outcomes. The trial includes patients who had a stroke within 4.5 hours and had taken a strong blood thinner within the last 48 hours. It has three arms: one group receives no medication (the current standard), one receives a low dose, and one receives the full dose. Singh said the trial uses a Bayesian design, meaning it adapts as data comes in. "If during the trial, the design is such that if we find that one arm is more harmful than the other, we drop that arm," she explained. "Because we don’t want to wait until the end to know there is a safety issue or a harm."

So far, about 150 of a planned 400 patients have been enrolled across 21 sites in Canada, with additional sites in Australia and trials set to begin in Europe, India and Korea. Singh said there have been no adverse effects reported among enrolled patients to date. When a patient arrives at the ED on blood thinners, they or their family are informed about the study. The patient provides verbal consent in the emergency department to receive the medication and enroll. Paperwork is completed later, and patients are followed up with a phone call 90 days after their stroke.

"The outcomes in terms of how they’re doing from their stroke and recovery is collected in 90 days," said Singh. "We give them a phone call and ask them how they’re doing. It’s a standardized questionnaire." She expects to reach the full sample size of 400 by 2027, after which final data will be compiled and presented at conferences. "So what it means is this trial, if it turns out to be positive, it’s going to open up and expand indications for thrombolytics," said Singh. "It’s going to be big because, you know, we can now offer the medication to people who are typically denied."

With files from Shared Health