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 language | English (US) |
|---|---|
| Pages (from-to) | 177-182 |
| Number of pages | 6 |
| Journal | Journal of Stroke and Cerebrovascular Diseases |
| Volume | 20 |
| Issue number | 3 |
| DOIs | |
| State | Published - May 2011 |
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Keywords
- acute ischemic stroke
- clinical trial
- Donepezil
- stroke recovery
ASJC Scopus subject areas
- Clinical Neurology
- Surgery
- Rehabilitation
- Cardiology and Cardiovascular Medicine
Cite this
Enhancing recovery after acute ischemic stroke with donepezil as an adjuvant therapy to standard medical care : Results of a phase iia clinical trial. / Barrett, Kevin M; Brott, Thomas G; Brown, Robert D Jr.; Carter, Rickey E.; Geske, Jennifer R.; Graff Radford, Neill R; McNeil, Rebecca B.; Meschia, James F.
In: Journal of Stroke and Cerebrovascular Diseases, Vol. 20, No. 3, 05.2011, p. 177-182.Research output: Contribution to journal › Article
}
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
UR - http://www.scopus.com/inward/record.url?scp=79955498599&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79955498599&partnerID=8YFLogxK
U2 - 10.1016/j.jstrokecerebrovasdis.2010.12.009
DO - 10.1016/j.jstrokecerebrovasdis.2010.12.009
M3 - Article
C2 - 21295494
AN - SCOPUS:79955498599
VL - 20
SP - 177
EP - 182
JO - Journal of Stroke and Cerebrovascular Diseases
JF - Journal of Stroke and Cerebrovascular Diseases
SN - 1052-3057
IS - 3
ER -