Multi-arm Optimization of Stroke Thrombolysis - MOST

Sep 10, 2024
Font Size
A
A
A
Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Kim A. Eagle, MD, MACC
Trial Sponsor:
National Institute of Neurological Disorders and Stroke
Date Published:
09/05/2024
Original Posted Date:
09/10/2024
References

Contribution To Literature:

The MOST trial failed to show that adjuvant argatroban or eptifibatide reduced disability when added to intravenous thrombolytic therapy for acute ischemic stroke.

Description:

The goal of the trial was to evaluate argatroban vs. eptifibatide vs. placebo among patients with acute ischemic stroke treated with intravenous thrombolytic therapy.

Study Design

  • Randomized
  • Parallel

Patients with acute ischemic stroke treated with intravenous thrombolytic therapy were randomized to argatroban (n = 59) vs. eptifibatide (n = 227) vs. placebo (n = 228).

Argatroban dosing was 100 μg/kg bolus, followed by 3 μg/kg/min for 12 hours. Eptifibatide dosing was 135 μg/kg, followed by 0.75 μg/kg/min for 2 hours.

  • Total number of enrollees: 514
  • Duration of follow-up: 90 days
  • Mean patient age: 66 years
  • Percentage female: 48%
  • Percentage with diabetes: 31%

Inclusion criteria:

  • Acute ischemic stroke treated with intravenous thrombolytic therapy within 3 hours of symptom onset
  • Able to receive study drug with 75 minutes of thrombolytic therapy

Other salient features/characteristics:

  • Endovascular thrombectomy planned at time of randomization: 48%

Principal Findings:

The trial was stopped early since criteria for futility were met. The maximum planned sample size was 1,200.

The primary outcome, modified Rankin scale score at 90 days, was 5.2 with argatroban vs. 6.3 with eptifibatide vs. 6.8 with placebo. A higher Rankin score indicates greater disability. The posterior probability that argatroban was superior to placebo was 0.002. The posterior probability that eptifibatide was better than placebo was 0.041.

Secondary outcomes:

  • Symptomatic intracranial hemorrhage: 4% with argatroban vs. 3% with eptifibatide vs. 2% with placebo
  • Mortality at 90 days: 24% with argatroban vs. 12% with eptifibatide group, vs. 8% with placebo

Interpretation:

Among patients with acute ischemic stroke treated with intravenous thrombolytic therapy, neither argatroban nor eptifibatide reduced disability compared with placebo. There were more deaths among argatroban than eptifibatide treated patients; however, the reason was unexplained since serious bleeding (symptomatic intracranial hemorrhage) was similar between the study groups.

References:

Adeoye O, Broderick J, Derdeyn CP, et al. Adjunctive Intravenous Argatroban or Eptifibatide for Ischemic Stroke. N Engl J Med 2024;391:810-20.

Clinical Topics: Vascular Medicine

Keywords: Disability Evaluation, Ischemic Stroke, Novel Agents, Thrombolytic Therapy


< Back to Listings