Those results were reported from the Multi-Arm Optimization of Stroke Thrombolysis (MOST) trial, which involved 79 sites in the United States. It was halted after an independent data and safety board analyzed results on the first 500 patients out of a planned 1,200 participants; the panel deemed it highly unlikely that a benefit would be found if the research was completed. The hope was for improvement in functional outcomes at 90 days.
“When we began the trial, we believed the medications would improve outcomes, so we were surprised with the negative results. However, we designed the trial to allow us to efficiently answer the question for two blood-thinning medications in one trial. We have definitely done that and are pleased with the ability to answer this question,” said lead author Opelus M. Adeoye, MD, MS, chair of the Department of Emergency Medicine at Washington University School of Medicine in St. Louis.
The MOST initiative sought to determine if araroba (100 µg/kg bolus followed by 3 µg/kg per minute for 12 hours) or eptifibatide (135 µg/kg bolus followed by 0.75 µg/kg/min infusion for 2 hours) resulted in improved 90-day modified Rankin scores (mRS) compared with placebo in acute ischemic stroke (AIS) patients treated with thrombolysis within 3 hours of symptom onset. The primary safety objective was defined as symptomatic intracranial hemorrhage (sICH) rates within 36 hours of randomization.
Designed as a three-arm, adaptive, phase III, single-blind, randomized, controlled clinical trial, the MOST researchers randomized patients to placebo, argatroban, or eptifibatide as soon as possible after consent, but no later than 75 minutes after thrombolysis was initiated. They assessed functional outcome at 90 days, the primary efficacy outcome, by centralized video adjudication of interviews of the patient and/or LAR using the Rankin Focused Assessment.
MOST opened to enrollment on October 15, 2019, with the first enrollment milestone for interim analysis scheduled at 500 subjects. That was reached on May 17, 2023, but the trial closed to accrual with 514 total subjects on July 5, 2023, following recommendations from the review panel.
“A lot of our approaches in stroke treatment were learned from how we treat heart attacks,” Dr. Adeoye pointed out. “In previous trials, we first tested to make sure these medications were safe for use in stroke and then launched MOST to confirm their safety and test whether they would work to improve functional outcomes and reduce disability after stroke.”
All MOST participants had strokes severe enough that rehabilitation would likely be needed. Across all three groups, 44% of the patients also were treated with thrombectomy, interventional removal of their clots.
For the 514 patients enrolled prior to the trial being halted, analysis found that neither of the two blood thinners significantly increased the risk of bleeding into the brain. At the same time, neither of the two blood thinners appeared to improve outcomes in the stroke survivors. On the 0 to 10 utility-weighted mRS scale, patients receiving placebo averaged 6.8, those receiving argatroban averaged 5.2, and those receiving eptifibatide averaged 6.3. (Those with a utility-weighted mRS scale of 6 are expected to have difficulty performing activities of daily living without assistance or support.)
Dr. Adeoye pointed out that researchers “were not able to address the possible benefit of giving these or similar blood thinners directly into an artery in the area of the stroke, rather than giving the medications systemically through a vein, as done in this trial.”
Thrombectomy patients are being studied to determine whether delivering blood thinners into the affected artery might improve outcomes.
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