Background & Aim
Mobility-focused rehabilitation is a broadly applicable intervention, typically starting in the acute stroke phase. Following the therapeutic uncertainty created by the findings of AVERT, AVERT DOSE1 aimed to determine the optimal safe and effective therapy regimens in patients with mild and moderate ischaemic stroke.
Methods and design
We designed a Multi-Arm Multi-Stage Covariate-Adjusted Response-Adaptive randomised trial of four different regimens of mobility training commenced within 48 hours of stroke in each of two severity strata: mild (NIHSS<7) and moderate (NIHSS 8-16) ischaemic stroke, with analysis of blinded outcomes at 3 (primary) and 6 months. Eligibility criteria were broad, while excluding those with severe premorbid disability (mRS>2). All mobility training (functional, task-specific, upright), continued until discharge or 14 days, provided by trained physiotherapists and supported by nurses, was protocolised, with four arms per stratum. Favourable outcome (mRS 0-2) at 3 months was primary.
Results
Trial stopped early due to funding constraints. Final participants were (total n=1000: mild n=637, moderate n=363) recruited until December 2025. Data lock with 3-month outcomes finalised March 2026. Fifty hospitals in seven countries (Australia, Brazil, India, Ireland, Malaysia, Singapore, United Kingdom) participated. Outcomes will be presented separately for mild and moderate strata using re-randomization tests given the adaptive trial design, together with frequentist confidence of the tested regimens being clinically meaningfully better than the reference regimen.
Conclusion
While closed early, our adaptive trial allowed an efficient evaluation of the safety and effectiveness of early mobility intervention for patients with mild and moderate ischaemic stroke.