Ongoing trial update 2019: Determining optimal early rehabilitation after stroke (avert dose).

Background and Aims: Our large international RCT of early rehabilitation (AVERT), provided evidence that early high intensity training interferes with stroke recovery (The Lancet, 2015), and that most patients may be responsive to therapy if the right dose is provided. (Neurology 2016). The aim of AVERT DOSE is to define the optimal early training regimens for people with mild and moderate ischaemic stroke. Method(s): Multi-Arm, Multi-Stage, Covariate-Adjusted, Response- Adaptive, randomised trial in two specified stroke severity strata. (Mild: NIHSS 0-7; Moderate: NIHSS 8-16). Patients are randomised to one of four mobility training regimens in each strata (including a pre-specified reference group), and the intervention is delivered for up to 14 days. Inclusion criteria: Ischaemic stroke within 48 hours, >=18 years. Exclusion criteria: Severe stroke, medically unwell, no evident mobility problems. We will recruit 2,700 patients from 8 countries. Primary Outcome: Identification of the intervention regimen that results in fewer disabled patients (mRS 0-2) at 3 months post-stroke. Blinded assessments will occur at 3 and 6 months. An adaptive sample size re-estimation provides 80% power to detect a 10% absolute treatment effect or larger compared to the pre-specified reference group, with a significance threshold of p=0.025 per stratum. Analyses will be intention-to-treat. Result(s): Australian National Mutual Acceptance HREC approval for Australia has been received. International collaborations, site selection and development of an online database are underway. Conclusion(s): AVERT DOSE will provide information about the dose and timing of early rehabilitation after ischaemic stroke onset. The results will be generalisable globally.