A Very Early Rehabilitation Trial after stroke (AVERT):: a Phase III, multicentre, randomised controlled trial

Background: Mobilising patients early after stroke [early mobilisation (EM)] is thought to contribute to the beneficial effects of stroke unit care but it is poorly defined and lacks direct evidence of benefit. Objectives: We assessed the effectiveness of frequent higher dose very early mobilisation (VEM) after stroke. Design: We conducted a parallel-group, single-blind, prospective randomised controlled trial with blinded end-point assessment using a web-based computer-generated stratified randomisation. Setting: The trial took place in 56 acute stroke units in five countries. Participants: We included adult patients with a first or recurrent stroke who met physiological inclusion criteria. Interventions: Patients received either usual stroke unit care (UC) or UC plus VEM commencing within 24 hours of stroke. Main outcome measures: The primary outcome was good recovery [modified Rankin scale (mRS) score of 0-2] 3 months after stroke. Secondary outcomes at 3 months were the mRS, time to achieve walking 50 m, serious adverse events, quality of life (QoL) and costs at 12 months. Tertiary outcomes included a dose-response analysis. Data sources: Patients, outcome assessors and investigators involved in the trial were blinded to treatment allocation. Results: We recruited 2104 (UK, n = 610; Australasia, n = 1494) patients: 1054 allocated to VEM and 1050 to UC. Intervention protocol targets were achieved. Compared with UC, VEM patients mobilised 4.8 hours [95% confidence interval (CI) 4.1 to 5.7 hours; p < 0.0001] earlier, with an additional three (95% CI 3.0 to 3.5; p < 0.0001) mobilisation sessions per day. Fewer patients in the VEM group (n = 480, 46%) had a favourable outcome than in the UC group (n = 525, 50%) (adjusted odds ratio 0.73, 95% CI 0.59 to 0.90; p = 0.004). Results were consistent between Australasian and UK settings. There were no statistically significant differences in secondary outcomes at 3 months and QoL at 12 months. Dose-response analysis found a consistent pattern of an improved odds of efficacy and safety outcomes in association with increased daily frequency of out-of-bed sessions but a reduced odds with an increased amount of mobilisation (minutes per day). Limitations: UC clinicians started mobilisation earlier each year altering the context of the trial. Other potential confounding factors included staff patient interaction. Conclusions: Patients in the VEM group were mobilised earlier and with a higher dose of therapy than those in the UC group, which was already early. This VEM protocol was associated with reduced odds of favourable outcome at 3 months cautioning against very early high-dose mobilisation. At 12 months, health-related QoL was similar regardless of group. Shorter, more frequent mobilisation early after stroke may be associated with a more favourable outcome