Fiona Ellery

Efficacy and safety of very early mobilisation within 24 h of stroke onset (AVERT): a randomised controlled trial.

BACKGROUND Early mobilisation after stroke is thought to contribute to the effects of stroke-unit care; however, the intervention is poorly defined and not underpinned by strong evidence. We aimed to compare the effectiveness of frequent, higher dose, very early mobilisation with usual care after stroke. METHODS We did this parallel-group, single-blind, randomised controlled trial at 56 acute stroke units in five countries. Patients (aged ≥18 years) with ischaemic or haemorrhagic stroke, first or recurrent, who met physiological criteria were randomly assigned (1:1), via a web-based computer generated block randomisation procedure (block size of six), to receive usual stroke-unit care alone or very early mobilisation in addition to usual care. Treatment with recombinant tissue plasminogen activator was allowed. Randomisation was stratified by study site and stroke severity. Patients, outcome assessors, and investigators involved in trial and data management were masked to treatment allocation. The primary outcome was a favourable outcome 3 months after stroke, defined as a modified Rankin Scale score of 0-2. We did analysis on an intention-to-treat basis. The trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12606000185561. FINDINGS Between July 18, 2006, and Oct 16, 2014, we randomly assigned 2104 patients to receive either very early mobilisation (n=1054) or usual care (n=1050); 2083 (99%) patients were included in the 3 month follow-up assessment. 965 (92%) patients were mobilised within 24 h in the very early mobilisation group compared with 623 (59%) patients in the usual care group. Fewer patients in the very early mobilisation group had a favourable outcome than those in the usual care group (n=480 [46%] vs n=525 [50%]; adjusted odds ratio [OR] 0·73, 95% CI 0·59-0·90; p=0·004). 88 (8%) patients died in the very early mobilisation group compared with 72 (7%) patients in the usual care group (OR 1·34, 95% CI 0·93-1·93, p=0·113). 201 (19%) patients in the very early mobilisation group and 208 (20%) of those in the usual care group had a non-fatal serious adverse event, with no reduction in immobility-related complications with very early mobilisation. INTERPRETATION First mobilisation took place within 24 h for most patients in this trial. The higher dose, very early mobilisation protocol was associated with a reduction in the odds of a favourable outcome at 3 months. Early mobilisation after stroke is recommended in many clinical practice guidelines worldwide, and our findings should affect clinical practice by refining present guidelines; however, clinical recommendations should be informed by future analyses of dose-response associations. FUNDING National Health and Medical Research Council, Singapore Health, Chest Heart and Stroke Scotland, Northern Ireland Chest Heart and Stroke, UK Stroke Association, National Institute of Health Research.

Prespecified dose-response analysis for A Very Early Rehabilitation Trial (AVERT)

Objective: Our prespecified dose-response analyses of A Very Early Rehabilitation Trial (AVERT) aim to provide practical guidance for clinicians on the timing, frequency, and amount of mobilization following acute stroke. Methods: Eligible patients were aged ≥18 years, had confirmed first (or recurrent) stroke, and were admitted to a stroke unit within 24 hours of stroke onset. Patients were randomized to receive very early and frequent mobilization, commencing within 24 hours, or usual care. We used regression analyses and Classification and Regression Trees (CART) to investigate the effect of timing and dose of mobilization on efficacy and safety outcomes, irrespective of assigned treatment group. Results: A total of 2,104 patients were enrolled, of whom 2,083 (99.0%) were followed up at 3 months. We found a consistent pattern of improved odds of favorable outcome in efficacy and safety outcomes with increased daily frequency of out-of-bed sessions (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.09 to 1.18, p < 0.001), keeping time to first mobilization and mobilization amount constant. Increased amount (minutes per day) of mobilization reduced the odds of a good outcome (OR 0.94, 95% CI 0.91 to 0.97, p < 0.001). Session frequency was the most important variable in the CART analysis, after prognostic variables age and baseline stroke severity. Conclusion: These data suggest that shorter, more frequent mobilization early after acute stroke is associated with greater odds of favorable outcome at 3 months when controlling for age and stroke severity. Classification of evidence: This study provides Class III evidence that shorter, more frequent early mobilization improves the chance of regaining independence after stroke.

AVERT2 (a very early rehabilitation trial, a very effective reproductive trigger): retrospective observational analysis of the number of babies born to trial staff

Objective To report the number of participants needed to recruit per baby born to trial staff during AVERT, a large international trial on acute stroke, and to describe trial management consequences. Design Retrospective observational analysis. Setting 56 acute stroke hospitals in eight countries. Participants 1074 trial physiotherapists, nurses, and other clinicians. Outcome measures Number of babies born during trial recruitment per trial participant recruited. Results With 198 site recruitment years and 2104 patients recruited during AVERT, 120 babies were born to trial staff. Births led to an estimated 10% loss in time to achieve recruitment. Parental leave was linked to six trial site closures. The number of participants needed to recruit per baby born was 17.5 (95% confidence interval 14.7 to 21.0); additional trial costs associated with each birth were estimated at 5736 Australian dollars on average. Conclusion The staff absences registered in AVERT owing to parental leave led to delayed trial recruitment and increased costs, and should be considered by trial investigators when planning research and estimating budgets. However, the celebration of new life became a highlight of the annual AVERT collaborators’ meetings and helped maintain a cohesive collaborative group. Trial registration Australian New Zealand Clinical Trials Registry no 12606000185561. Disclaimer Participation in a rehabilitation trial does not guarantee successful reproductive activity.

Implementing a complex rehabilitation intervention in a stroke trial: a qualitative process evaluation of AVERT

BackgroundThe implementation of multidisciplinary stroke rehabilitation interventions is challenging, even when the intervention is evidence-based. Very little is known about the implementation of complex interventions in rehabilitation clinical trials.The aim of study was to better understand how the implementation of a rehabilitation intervention in a clinical trial within acute stroke units is experienced by the staff involved. This qualitative process evaluation was part of a large Phase III stroke rehabilitation trial (AVERT).MethodsA descriptive qualitative approach was used. We purposively sampled 53 allied health and nursing staff from 19 acute stroke units in Australia, New Zealand and Scotland. Semi-structured interviews were conducted by phone, voice-internet, or face to face. Digitally recorded interviews were transcribed and analysed by two researchers using rigorous thematic analysis.ResultsOur analysis uncovered ten important themes that provide insight into the challenges of implementing complex new rehabilitation practices within complex care settings, plus factors and strategies that assisted implementation. Themes were grouped into three main categories: staff experience of implementing the trial intervention, barriers to implementation, and overcoming the barriers. Participation in the trial was challenging but had personal rewards and improved teamwork at some sites. Over the years that the trial ran some staff perceived a change in usual care. Barriers to trial implementation at some sites included poor teamwork, inadequate staffing, various organisational barriers, staff attitudes and beliefs, and patient-related barriers. Participants described successful implementation strategies that were built on interdisciplinary teamwork, education and strong leadership to ‘get staff on board’, and developing different ways of working.ConclusionsThe AVERT stroke rehabilitation trial required commitment to deliver an intervention that needed strong collaboration between nurses and physiotherapists and was different to current care models. This qualitative process evaluation contributes unique insights into factors that may be critical to successful trials teams, and as AVERT was a pragmatic trial, success factors to delivering complex intervention in clinical practice.Trial registrationAVERT registered with Australian New Zealand Clinical Trials Registry ACTRN12606000185561.

A randomized controlled trial of very early rehabilitation in speech after stroke

Rationale The efficacy of rehabilitation therapy for aphasia caused by stroke is uncertain. Aims and hypothesis The Very Early Rehabilitation of Speech (VERSE) trial aims to determine if intensive prescribed aphasia therapy (VERSE) is more effective and cost saving than non-prescribed, intensive (usual care-plus) and non-intensive usual care (UC) therapy when started within 15 days of stroke onset and continued daily over four weeks. We hypothesize that aphasia therapy when started very early after stroke and delivered daily could enhance recovery of communication compared with UC. Sample size estimates A total of 246 participants (82 per arm) will provide 80% power to detect a 4.4% improvement on aphasia quotient between VERSE and UC plus at a significance level of α = 0.05. Setting Acute-care hospitals and accompanying rehabilitation services throughout Australia, 2014–2017. Design Three-arm, prospective, randomized, parallel group, open-label, blinded endpoint assessment (PROBE) trial. Participants Acute stroke in previous 14 days and aphasia diagnosed by aphasia quotient (AQ) of the Western Aphasia Battery (WAB). Randomization Computer-generated blocked randomization procedure stratified by aphasia severity according to Western Aphasia Battery, to one of three arms. Intervention All participants receive UC—usual ward-based aphasia therapy. Arm 1: UC—no additional therapy; Arm 2: UC-plus usual ward-based therapy; Arm 3: VERSE therapy—a prescribed and structured aphasia therapy program. Arms 2 and 3 receive a total of 20 additional sessions (45–60 min, provided daily) of aphasia therapy. The additional intervention must be provided before day 50 post stroke. Study outcome measures The aphasia quotient of Western Aphasia Battery at 12 weeks post stroke. Secondary outcomes include discourse measures, the Stroke and Aphasia Quality of Life Scale-39 and the Aphasia Depression Rating Scale at 12 and 26 weeks. Economic evaluation Incremental cost-effectiveness ratios at 26 weeks will be reported. Discussion This trial is designed to test whether the intensive and prescribed VERSE intervention is effective in promoting maximum recovery and preventing costly health complications in a vulnerable population of survivors of stroke. It will also provide novel, prospective, aphasia specific cost-effectiveness data to guide future policy development for this population.

A Bahasa Malaysia version of the Montreal Cognitive Assessment: Validation in stroke

BACKGROUND Many stroke research trials do not include assessment of cognitive function. A Very Early Rehabilitation Trial (AVERT) is an international multicenter study that includes the Montreal Cognitive Assessment (MoCA) as an outcome. At the Malaysian AVERT site, completion of the MoCA has been limited by low English proficiency in some participants. We aimed to develop a Bahasa Malaysia (BM) version of the MoCA and to validate it in a stroke population. METHODS The original English version of the MoCA was translated into BM and then back-translated to ensure accuracy. Feasibility testing in a group of stroke patients prompted minor changes to the BM MoCA. In the validation phase, a larger group of bilingual stroke patients completed both the original English MoCA and the finalized BM MoCA, with presentation order counter-balanced. RESULTS Forty stroke patients participated, with a mean age of 57.2 (SD = 10.3). Agreement between BM MoCA and English MoCA was strong (intra-class correlation coefficient = 0.81, 95% CI 0.68-0.90). Scores on BM MoCA were slightly higher than scores on English MoCA (median absolute difference = 2.0, IQR 0-3.5), and this difference was present regardless of which version was completed first. CONCLUSIONS The existence of a validated BM version of the MoCA will be of major benefit to clinicians and researchers in Malaysia and the wider South-east Asian region, where the Malay language is used by over 200 million people.

Statistical analysis plan (SAP) for the Very Early Rehabilitation in Speech (VERSE) after stroke trial: an international 3-arm clinical trial to determine the effectiveness of early, intensive, prescribed, direct aphasia therapy

Background Limited evidence exists to support very early intensive aphasia rehabilitation after stroke. VERSE is a PROBE trial designed to determine whether two types of intensive aphasia therapy, beginning within 14 days of acute stroke, provide greater therapeutic and cost-effectiveness than usual care. Objective To publish the detailed statistical analysis plan for the VERSE trial prior to unblinding. This statistical analysis plan was based on the published and registered VERSE trial protocol and was developed by the blinded steering committee and management team, led by the trial statistician. This plan was developed using outcome measures and trial data collection forms. Results The VERSE statistical analysis plan is consistent with reporting standards for clinical trials and provides for clear and open reporting. Conclusions Publication of a statistical analysis plan serves to reduce potential trial reporting bias and outlines transparent pre-specified analyses. Australian New Zealand Clinical Trials Registry (ANZCTR) Registration number: ACTRN12613000776707; Universal Trial Number (UTN) is U1111-1145-4130.