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.
- Definite or probable acute ischemic cerebrovascular syndrome (AICS), as defined by Kidwell et al (Stroke. 2003;34:2995-8).
- Experimental treatment started within 24 hours of onset of symptoms.
- Age ≥ 18 years.
- Ability and willingness to return for follow-up visits.
- Willingness of an available informant who knows the patient well to participate in informant-based questionnaires for the duration of the follow-up period.
- Living in independent or semi-independent living situation before the stroke.
- Fluent in English before the stroke.
- Provides written informed consent.
- Near visual acuity of at least 20/200 in at least one eye.
- Auditory acuity of at least having the ability to detect finger rubbing in at least one ear.
- Parkinson's disease or restless leg syndrome.
- Partial or generalized seizures.
- No acute decompensated heart failure
- Routinely requiring daytime supplemental oxygen before the stroke; study participants on continuous positive air pressure (CPAP) for obstructive sleep apnea remain eligible.
- Gastrointestinal or genitourinary surgery within 1 month of screening.
- Gastrointestinal bleeding.
- Syncope or symptomatic bradycardia.
- Creatinine ≥ 3.5 mg/dL or requiring dialysis.
- Peptic ulcer disease.
- Tracheostomy or endotracheal intubation.
- Taking donepezil or other acetylcholinesterase inhibitor at screening.
Patients will begin taking donepezil (Aricept) within 24 hours of their stroke. They will be required to return to Mayo Clinic at 30 days, 60 days, 90 days and 6 months after their stroke. Patients will receive medication refills at the 30- and 60-day visits. During all study visits, any problems with the medication and any new medical conditions will be recorded. Patients will complete neuropsych testing at the 30-day, 60-day and 6-month visit.
4 visits over 6 months
Last updated: 10/04/2012
NCT ID: NCT00805792