Enhancing recovery after acute ischemic stroke with donepezil as an adjuvant therapy to standard medical care

Results of a phase iia clinical trial

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background: Our aim was to assess the safety, tolerability, and efficacy signal of early donepezil administration with regard to enhancing recovery in a diverse acute ischemic stroke population. Methods: This was a multicenter, single-arm, National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator trial-controlled, modified 2-stage adaptive clinical trial set in 2 tertiary care hospitals in the United States. Adults with ischemic stroke treated within 24 hours after onset of symptoms were included. The intervention studied was donepezil 5 mg/day for 30 days, followed by an increase to 10 mg/day for 60 days. Our main outcome measures included treatment-related adverse events and side effects. The primary favorable outcome was a 90-day National Institutes of Health Stroke Scale (NIHSS) score ≤1. Neurologic, cognitive, functional, and psychological outcomes were assessed longitudinally. Results: Thirty-three adults (median age 66 years; 59% female; 39% received tissue plasminogen activator) initiated treatment with donepezil. There were no treatment-related serious adverse events. Three participants (9%) discontinued donepezil because of side effects and 3 participants (9%) required a reduction to 5 mg/day after titration to 10 mg/day. Fifteen participants (45%) had a favorable outcome (NIHSS score ≤1 at day 90), and the study met prespecified criteria for continuing to a randomized trial (P < .10). Statistically significant improvements from baseline were observed with several secondary cognitive measures, including the Trail Making Tests and Mini-Mental State Exam (P < .01 for both). Conclusions: Adjuvant donepezil therapy initiated within 24 hours of acute ischemic stroke was safe and tolerated at 5 mg/day to 10 mg/day. The study met a priori criteria to move forward with a randomized clinical trial.

Original languageEnglish (US)
Pages (from-to)177-182
Number of pages6
JournalJournal of Stroke and Cerebrovascular Diseases
Volume20
Issue number3
DOIs
StatePublished - May 2011

Fingerprint

Stroke
Clinical Trials
National Institutes of Health (U.S.)
Tissue Plasminogen Activator
National Institute of Neurological Disorders and Stroke
Trail Making Test
Therapeutics
Tertiary Healthcare
Tertiary Care Centers
Nervous System
Randomized Controlled Trials
Outcome Assessment (Health Care)
donepezil
Psychology
Safety
Population

Keywords

  • acute ischemic stroke
  • clinical trial
  • Donepezil
  • stroke recovery

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery
  • Rehabilitation
  • Cardiology and Cardiovascular Medicine

Cite this

@article{074f4533ef094f03838a186f92a0e003,
title = "Enhancing recovery after acute ischemic stroke with donepezil as an adjuvant therapy to standard medical care: Results of a phase iia clinical trial",
abstract = "Background: Our aim was to assess the safety, tolerability, and efficacy signal of early donepezil administration with regard to enhancing recovery in a diverse acute ischemic stroke population. Methods: This was a multicenter, single-arm, National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator trial-controlled, modified 2-stage adaptive clinical trial set in 2 tertiary care hospitals in the United States. Adults with ischemic stroke treated within 24 hours after onset of symptoms were included. The intervention studied was donepezil 5 mg/day for 30 days, followed by an increase to 10 mg/day for 60 days. Our main outcome measures included treatment-related adverse events and side effects. The primary favorable outcome was a 90-day National Institutes of Health Stroke Scale (NIHSS) score ≤1. Neurologic, cognitive, functional, and psychological outcomes were assessed longitudinally. Results: Thirty-three adults (median age 66 years; 59{\%} female; 39{\%} received tissue plasminogen activator) initiated treatment with donepezil. There were no treatment-related serious adverse events. Three participants (9{\%}) discontinued donepezil because of side effects and 3 participants (9{\%}) required a reduction to 5 mg/day after titration to 10 mg/day. Fifteen participants (45{\%}) had a favorable outcome (NIHSS score ≤1 at day 90), and the study met prespecified criteria for continuing to a randomized trial (P < .10). Statistically significant improvements from baseline were observed with several secondary cognitive measures, including the Trail Making Tests and Mini-Mental State Exam (P < .01 for both). Conclusions: Adjuvant donepezil therapy initiated within 24 hours of acute ischemic stroke was safe and tolerated at 5 mg/day to 10 mg/day. The study met a priori criteria to move forward with a randomized clinical trial.",
keywords = "acute ischemic stroke, clinical trial, Donepezil, stroke recovery",
author = "Barrett, {Kevin M} and Brott, {Thomas G} and Brown, {Robert D Jr.} and Carter, {Rickey E.} and Geske, {Jennifer R.} and {Graff Radford}, {Neill R} and McNeil, {Rebecca B.} and Meschia, {James F}",
year = "2011",
month = "5",
doi = "10.1016/j.jstrokecerebrovasdis.2010.12.009",
language = "English (US)",
volume = "20",
pages = "177--182",
journal = "Journal of Stroke and Cerebrovascular Diseases",
issn = "1052-3057",
publisher = "W.B. Saunders Ltd",
number = "3",

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TY - JOUR

T1 - Enhancing recovery after acute ischemic stroke with donepezil as an adjuvant therapy to standard medical care

T2 - Results of a phase iia clinical trial

AU - Barrett, Kevin M

AU - Brott, Thomas G

AU - Brown, Robert D Jr.

AU - Carter, Rickey E.

AU - Geske, Jennifer R.

AU - Graff Radford, Neill R

AU - McNeil, Rebecca B.

AU - Meschia, James F

PY - 2011/5

Y1 - 2011/5

N2 - Background: Our aim was to assess the safety, tolerability, and efficacy signal of early donepezil administration with regard to enhancing recovery in a diverse acute ischemic stroke population. Methods: This was a multicenter, single-arm, National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator trial-controlled, modified 2-stage adaptive clinical trial set in 2 tertiary care hospitals in the United States. Adults with ischemic stroke treated within 24 hours after onset of symptoms were included. The intervention studied was donepezil 5 mg/day for 30 days, followed by an increase to 10 mg/day for 60 days. Our main outcome measures included treatment-related adverse events and side effects. The primary favorable outcome was a 90-day National Institutes of Health Stroke Scale (NIHSS) score ≤1. Neurologic, cognitive, functional, and psychological outcomes were assessed longitudinally. Results: Thirty-three adults (median age 66 years; 59% female; 39% received tissue plasminogen activator) initiated treatment with donepezil. There were no treatment-related serious adverse events. Three participants (9%) discontinued donepezil because of side effects and 3 participants (9%) required a reduction to 5 mg/day after titration to 10 mg/day. Fifteen participants (45%) had a favorable outcome (NIHSS score ≤1 at day 90), and the study met prespecified criteria for continuing to a randomized trial (P < .10). Statistically significant improvements from baseline were observed with several secondary cognitive measures, including the Trail Making Tests and Mini-Mental State Exam (P < .01 for both). Conclusions: Adjuvant donepezil therapy initiated within 24 hours of acute ischemic stroke was safe and tolerated at 5 mg/day to 10 mg/day. The study met a priori criteria to move forward with a randomized clinical trial.

AB - Background: Our aim was to assess the safety, tolerability, and efficacy signal of early donepezil administration with regard to enhancing recovery in a diverse acute ischemic stroke population. Methods: This was a multicenter, single-arm, National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator trial-controlled, modified 2-stage adaptive clinical trial set in 2 tertiary care hospitals in the United States. Adults with ischemic stroke treated within 24 hours after onset of symptoms were included. The intervention studied was donepezil 5 mg/day for 30 days, followed by an increase to 10 mg/day for 60 days. Our main outcome measures included treatment-related adverse events and side effects. The primary favorable outcome was a 90-day National Institutes of Health Stroke Scale (NIHSS) score ≤1. Neurologic, cognitive, functional, and psychological outcomes were assessed longitudinally. Results: Thirty-three adults (median age 66 years; 59% female; 39% received tissue plasminogen activator) initiated treatment with donepezil. There were no treatment-related serious adverse events. Three participants (9%) discontinued donepezil because of side effects and 3 participants (9%) required a reduction to 5 mg/day after titration to 10 mg/day. Fifteen participants (45%) had a favorable outcome (NIHSS score ≤1 at day 90), and the study met prespecified criteria for continuing to a randomized trial (P < .10). Statistically significant improvements from baseline were observed with several secondary cognitive measures, including the Trail Making Tests and Mini-Mental State Exam (P < .01 for both). Conclusions: Adjuvant donepezil therapy initiated within 24 hours of acute ischemic stroke was safe and tolerated at 5 mg/day to 10 mg/day. The study met a priori criteria to move forward with a randomized clinical trial.

KW - acute ischemic stroke

KW - clinical trial

KW - Donepezil

KW - stroke recovery

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