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A phase III, multi-arm multi-stage covariate-adjusted response-adaptive randomized trial to determine optimal early mobility training after stroke (AVERT DOSE)
Bernhardt, Julie Churilov, Leonid Dewey, Helen Donnan, Geoffrey Ellery, Fiona English, Carolie Gao, Lan Hayward, Kathryn Horgan, Frances Indredavik, Bent
Bernhardt, Julie
Churilov, Leonid
Dewey, Helen
Donnan, Geoffrey
Ellery, Fiona
English, Carolie
Gao, Lan
Hayward, Kathryn
Horgan, Frances
Indredavik, Bent
Author
Bernhardt, Julie
Churilov, Leonid
Dewey, Helen
Donnan, Geoffrey
Ellery, Fiona
English, Carolie
Gao, Lan
Hayward, Kathryn
Horgan, Frances
Indredavik, Bent
Johns, Hannah
Langhorne, Peter
Lindley, Richard
Martins, Sheila
Ali Katijjahbe, Md
Middleton, Sandy
Moodie, Marj
Pandian, Jeyaraj
Parsons, Brooke
Robinson, Thompson
Srikanth, Vilandai
Thijs, Vincent
Churilov, Leonid
Dewey, Helen
Donnan, Geoffrey
Ellery, Fiona
English, Carolie
Gao, Lan
Hayward, Kathryn
Horgan, Frances
Indredavik, Bent
Johns, Hannah
Langhorne, Peter
Lindley, Richard
Martins, Sheila
Ali Katijjahbe, Md
Middleton, Sandy
Moodie, Marj
Pandian, Jeyaraj
Parsons, Brooke
Robinson, Thompson
Srikanth, Vilandai
Thijs, Vincent
Abstract
Rationale:
The evidence base for acute post-stroke rehabilitation is inadequate and global guideline recommendations vary.
Aim:
To define optimal early mobility intervention regimens for ischemic stroke patients of mild and moderate severity.
Hypotheses:
Compared with a prespecified reference arm, the optimal dose regimen(s) will result in more participants experiencing little or no disability (mRS 0–2) at 3 months post-stroke (primary), fewer deaths at 3 months, fewer and less severe complications during the intervention period, faster recovery of unassisted walking, and better quality of life at 3 months (secondary). We also hypothesize that these regimens will be more cost-effective.
Sample size estimates:
For the primary outcome, recruitment of 1300 mild and 1400 moderate participants will yield 80% power to detect a 10% risk difference.
Methods and design:
Multi-arm multi-stage covariate-adjusted response-adaptive randomized trial of mobility training commenced within 48 h of stroke in mild (NIHSS < 7) and moderate (NIHSS 8–16) stroke patient strata, with analysis of blinded outcomes at 3 (primary) and 6 months. Eligibility criteria are broad, while excluding those with severe premorbid disability (mRS > 2) and hemorrhagic stroke. With four arms per stratum (reference arm retained throughout), only the single treatment arm demonstrating the highest proportion of favorable outcomes at the first stage will proceed to the second stage in each stratum, resulting in a final comparison with the reference arm. Three prognostic covariates of age, geographic region and reperfusion interventions, as well as previously observed mRS 0–2 responses inform the adaptive randomization procedure. Participants randomized receive prespecified mobility training regimens (functional task-specific), provided by physiotherapists/nurses until discharge or 14 days. Interventions replace usual mobility training. Fifty hospitals in seven countries (Australia, Malaysia, United Kingdom, Ireland, India, Brazil, Singapore) are expected to participate.
Summary:
Our novel adaptive trial design will evaluate a wider variety of mobility regimes than a traditional two-arm design. The data-driven adaptions during the trial will enable a more efficient evaluation to determine the optimal early mobility intervention for patients with mild and moderate ischemic stroke.
Keywords
acute, stroke, mobility training, clinical trial
Date
2023
Type
Journal article
Journal
International Journal of Stroke
Book
Volume
18
Issue
6
Page Range
745-750
Article Number
ACU Department
Nursing Research Institute
Faculty of Health Sciences
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
License
All rights reserved
File Access
Controlled