Phase 3 Study to Evaluate the Efficacy and Safety of Intravenous BIIB093 (Glibenclamide) for Severe Cerebral Edema Following Large Hemispheric Infarction
Condition: Brain Edema; Stroke, Acute
MeSH terms: Stroke; Brain Edema; Infarction; Edema
Intervention: BIIB093; Placebo
Intervention description: Administered as specified in the treatment arm.; Administered as specified in the treatment arm.
Intervention MeSH terms: Glyburide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 535.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Infarction; Cerebrovascular Disorders; Brain Diseases; Pathological Processes Necrosis; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Glyburide; Hypoglycemic Agents; Physiological Effects of Drugs

Summary:

      The primary objective of Part 1 of the study is to determine if BIIB093 improves functional
      outcome at Day 90 as measured by the modified Rankin Scale (mRS) when compared with placebo
      in participants with Large Hemispheric Infarction (LHI). The secondary objectives of Part 1
      of the study are to determine if BIIB093 improves overall survival at Day 90 when compared
      with placebo, if BIIB093 improves functional outcome at Day 90 on the mRS dichotomized 0-4
      vs. 5-6 when compared with placebo, if BIIB093 reduces midline shift at 72 hours (or at time
      of decompressive craniectomy [DC] or comfort measures only [CMO], if earlier) when compared
      with placebo, and to evaluate the safety and tolerability of BIIB093 in participants with
      LHI.

      The objectives of Part 2 of the study are to evaluate long-term disability following LHI, to
      evaluate long-term outcome measures of clinical function, quality of life, and healthcare
      utilization, and to assess the safety of BIIB093 in subjects with LHI during the follow-up
      period.
    

Eligibility criteria:

        Inclusion Criteria:

          1. A clinical diagnosis of acute ischemic stroke in the middle cerebral artery (MCA)
             territory.

          2. A large hemispheric infarction defined as; lesion volume of 80 to 300 centimeters
             cubed (cm^3) on magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI), or
             computed tomography perfusion (CTP), or an Alberta Stroke Program Early CT Score
             (ASPECTS) of 1 to 5 with involvement of at least 2 defined cortical regions.

          3. Screening National Institutes of Health Stroke Scale (NIHSS) >=10.

          4. At the time of randomization, and in the Investigator's judgement, it must be feasible
             for study drug treatment infusion to be initiated no later than 10 hours after time of
             symptom onset, if known, or the time last known normal.

               -  Participants who wake with stroke may be included if neurological and other
                  exclusion criteria are satisfied. The time of stroke onset is to be taken as the
                  midpoint between sleep onset (or last known to be normal) and time of waking.

          5. For participants who receive thrombectomy, inclusion into the study must be based on
             post-thrombectomy MRI-DWI.

        Exclusion Criteria:

          1. Participant is likely to have supportive care withdrawn on the first day.

          2. Commitment to decompressive craniectomy (DC) prior to enrollment.

          3. Evidence of concurrent infarction in the contralateral hemisphere sufficiently serious
             so as to affect functional outcome.

        NOTE: Other protocol defined Inclusion/Exclusion criteria may apply