Mayo Acute Stroke Trial for Enhancing Recovery "MASTER"

Completed

Phase 2 Results

Trial Description

This study involves treating patients that have suffered an acute ischemic stroke with the medication donepezil (Aricept ®). The hypothesis is that taking donepezil (FDA-approved for the treatment of Alzheimer's Disease) for the first 90 days following a stroke enhances recovery.

Detailed Description

We hypothesize that donepezil (5 mg per day, titrated up to 10 mg per day as tolerated) will enhance recovery following stroke by improving attention, learning and memory thereby enhancing rehabilitation. The null hypothesis is that the probability of a favorable outcome among post-stroke donepezil users is equal to that observed among similar participants in an existing National Institutes of Neurological Disorders and Stroke (NINDS) resource, the Phase III clinical trial of Tissue Plasminogen Activator (tPA) for acute ischemic stroke. The NINDS tPA stroke trial has been used as historical control data in pilot trials of reperfusion and neuroprotection.
The MASTER trial will be a multicenter, single-arm NINDS Recominant tPA trial-controlled, modified 2-stage adaptive clinical trial set in 2 tertiary care hospitals in the United States. Participants will be men and women with acute (< 24 hours of onset of symptoms) ischemic stroke. A favorable outcome will be defined as National Institutes of Health Stroke Scale (NIHSS) values of 0 or 1 at 90 days post-stroke.

Conditions

Interventions

  • Donepezil hydrochloride (Aricept ®)Behavioral
    Intervention Desc: Reversible inhibitor of acetylcholinesterase.
  • Donepezil Drug
    Other Names: Aricept
    Intervention Desc: Study participants will be treated with donepezil orally at an initial dose of 5 mg daily for the first 4 weeks, then increased at their 30-day visit by 5 mg to a maximum dose of 10 mg daily, if tolerated. If the participant does not tolerate the 10 mg dose, they will remain on 5 mg through the course of the study.
    ARM 1: Kind: Experimental
    Label: Donepezil
    Description: Participants received treatment with donepezil within 24 hours after the onset of ischemic stroke symptoms. Participants received donepezil 5 mg/day for 30 days, followed by an increase to 10 mg/day for 60 days.

Trial Design

  • Masking: Open Label
  • Purpose: Treatment
  • Endpoint: Efficacy Study
  • Intervention: Single Group Assignment

Patient Involvement

Study participants will be treated with donepezil orally at an initial dose of 5 mg daily for the first 4 weeks, then increased at their 30-day visit by 5 mg to a maximum dose of 10 mg daily, if tolerated. If the participant does not tolerate the 10 mg dose, they will remain on 5 mg through the course of the study.

Outcomes

Type Measure Time Frame Safety Issue
Primary The primary outcome measure is 90-day status, categorized as favorable/unfavorable. A favorable outcome will be defined as NIHSS values of 0 or 1 at 90 days, while an unfavorable outcome will be defined as NIHSS of 2 or higher at 90 days post-stroke.
Secondary Secondary outcome measures include 6-month post-stroke status and the following neuropsychological assessments: IQCODE-SF, GOS, mRS, BI, MMSE, RBANS, COWAT, BDI-II, NPI-Q, and Trail Making Tests A & B.
Secondary Secondary outcome measures include 6-month post-stroke status and the following neuropsychological assessments: IQCODE-SF, GOS, mRS, BI, MMSE, RBANS, COWAT, BDI-II, NPI-Q, and Trail Making Tests A & B. 6 months No
Primary Percent of Participants With National Institutes of Health Stroke Scale (NIHSS) Score = 0 or 1 at Day 90 90 days post-stroke No
Secondary Change in Mean National Institutes of Health Stroke Scale (NIHSS) Score at 90 Days Post-stroke baseline, 90 days post-stroke No
Secondary Change in Mean Barthel Index of Activities of Daily Living Score at 90 Days Post-stroke baseline, 90 days post-stroke No
Secondary Change in Mean Score on Mini Mental State Exam at 90 Days Post-stroke baseline, 90 days post-stroke No
Secondary Change in Time to Complete Neuropsychological Trail Making Tests A and B at 90 Days Post-stroke baseline, 90 days post-stroke No

Sponsors