10.25384/SAGE.C.6375054
Julie Bernhardt
Julie
Bernhardt
Leonid Churilov
Leonid
Churilov
Helen Dewey
Helen
Dewey
Geoffrey Donnan
Geoffrey
Donnan
Fiona Ellery
Fiona
Ellery
Florey Institute of Neuroscience and Mental Health
Coralie English
Coralie
English
University of Newcastle Australia
Hunter Medical Research Institute
Florey Institute of Neuroscience and Mental Health
Lan Gao
Lan
Gao
Deakin University
University of Newcastle Australia
Peking University First Hospital
Kathryn Hayward
Kathryn
Hayward
Frances Horgan
Frances
Horgan
Royal College of Surgeons in Ireland
Bent Indredavik
Bent
Indredavik
St Olav's University Hospital
Norwegian University of Science and Technology
Hannah Johns
Hannah
Johns
Peter Langhorne
Peter
Langhorne
University of Glasgow
Richard Lindley
Richard
Lindley
Sheila Martins
Sheila
Martins
Md Ali Katijjahbe
Md
Ali Katijjahbe
Sandy Middleton
Sandy
Middleton
Australian Catholic University
St Vincent's Hospital
Marj Moodie
Marj
Moodie
Deakin University
Jeyaraj Pandian
Jeyaraj
Pandian
Brooke Parsons
Brooke
Parsons
Thompson Robinson
Thompson
Robinson
University of Leicester
Velandai Srikanth
Velandai
Srikanth
Monash University
Peninsula Health
Vincent Thijs
Vincent
Thijs
A phase III, multi-arm multi-stage covariate-adjusted response-adaptive randomized trial to determine optimal early mobility training after stroke (AVERT DOSE)
<div>Rationale:<p>The evidence base for acute post-stroke rehabilitation is inadequate and global guideline recommendations vary.</p>Aim:<p>To define optimal early mobility intervention regimens for ischemic stroke patients of mild and moderate severity.</p>Hypotheses:<p>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.</p>Sample size estimates:<p>For the primary outcome, recruitment of 1300 mild and 1400 moderate participants will yield 80% power to detect a 10% risk difference.</p>Methods and design:<p>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.</p>Summary:<p>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.</p></div>
Cardiology
Medicine
110904 Neurology and Neuromuscular Diseases
SAGE Journals
2023
2023-01-09
2023-01-09
Collection
10.1177/17474930221142207
CC BY 4.0