A groundbreaking clinical trial challenged long-held beliefs about stroke recovery, revealing that when it comes to rehabilitation, more and sooner isn't always better.
Imagine the scene: a patient arrives at the hospital after suffering a stroke. For decades, conventional wisdom has suggested that getting patients out of bed and moving as early as possible would speed their recovery. But what if this well-intentioned practice was actually doing more harm than good? This was the startling possibility explored by one of the largest stroke rehabilitation trials ever conducted—the AVERT trial 1 .
Stroke remains a leading cause of death and disability worldwide 3 . The management of stroke patients has progressed greatly in recent decades, with several interventions providing good evidence of benefit, including stroke unit care, aspirin for ischemic stroke, intravenous thrombolysis, and mechanical thrombectomy 2 .
For years, early mobilisation—starting out-of-bed activities like sitting, standing, and walking soon after stroke—was widely considered a crucial component of effective stroke unit care 2 . The biological rationale seemed sound: we know bed rest has harmful effects on cardiovascular, respiratory, muscular, skeletal, and immune systems across many conditions 2 .
Concepts of brain recovery suggest a narrow "window of opportunity" for repair
Complications from immobility are common after stroke
Concerns about impaired cerebral blood flow in first 24 hours
However, some clinicians voiced concerns about potential harms, particularly in the first 24 hours after stroke 2 . These concerns included fears that raising a patient's head early after stroke might impair cerebral blood flow or, in cases of intracerebral hemorrhage, increase the risk of further bleeding 2 . It was these uncertainties that prompted researchers to launch A Very Early Rehabilitation Trial (AVERT)—a definitive investigation that would challenge conventional thinking about stroke rehabilitation 2 .
The AVERT Phase III trial was designed as a pragmatic, international, multicenter, Phase III randomized controlled trial with the power to definitively evaluate the efficacy and safety of very early mobilisation (VEM) after stroke 1 2 . The trial was conducted across 56 acute stroke units in five countries (UK, Australia, New Zealand, Singapore, and Malaysia), ultimately recruiting 2,104 patients 1 .
To investigate whether a protocol implementing very early mobilisation (commencing within 24 hours of stroke) with frequent out-of-bed activity would lead to better outcomes compared with usual care, which traditionally started later 4 .
56 acute stroke units across 5 countries: UK, Australia, New Zealand, Singapore, and Malaysia with 2,104 participants recruited.
The researchers aimed to include a broad range of acute stroke patients, making the findings highly applicable to real-world clinical practice 4 .
Participants were randomly assigned to one of two groups:
Usual care plus a specific protocol of out-of-bed activities commencing within 24 hours of stroke
Standard stroke unit care
The randomisation process was carefully designed to ensure balanced groups, stratified by study site and stroke severity 4 .
| Tool/Measure | Function in the Trial |
|---|---|
| Modified Rankin Scale (mRS) | Primary outcome measure assessing degree of disability or dependence in daily activities 1 |
| NIH Stroke Scale (NIHSS) | Measured stroke severity at baseline; used to stratify randomisation 4 |
| Mobility Scale for Acute Stroke (MSAS) | Assessed mobility status 4 |
| Star Cancellation Test | Screening tool to detect unilateral spatial neglect 4 |
| Web-based randomisation system | Secure computer-generated allocation to treatment groups with stratification by site and stroke severity 4 |
| Online data capture system | Recorded mobilisation activities and trial data 4 |
The VEM protocol had four key features that distinguished it from usual care 4 :
It had to begin within 24 hours of stroke onset
The focus had to be on sitting, standing, and walking activities (out of bed)
Patients received at least three out-of-bed sessions per day in addition to usual care
Nursing and physiotherapy mobilisations were tailored each day according to the patient's functional level
The intervention was titrated according to functional ability levels, with specific targets for patients at different recovery stages 4 . For example, low-functioning dependent patients had a target of active sitting with assistance, while higher-functioning patients would work on standing and walking 4 . The protocol continued for 14 days or until discharge from the stroke unit, whichever came first 4 .
The VEM protocol was delivered by nurses and physiotherapists and continued for 14 days or until discharge
When the results were analyzed, they sent shockwaves through the stroke rehabilitation community. Contrary to the researchers' hypotheses, the VEM approach resulted in fewer patients achieving a favorable outcome compared to usual care 1 .
The primary outcome—good recovery defined as a modified Rankin Scale score of 0-2 at 3 months after stroke—was observed in 46% of the VEM group compared to 50% of the usual care group 1 . This represented a statistically significant reduction in the odds of a favorable outcome with the very early, higher-dose mobilisation protocol 1 .
| Outcome Measure | Very Early Mobilisation (VEM) Group | Usual Care (UC) Group | Statistical Significance |
|---|---|---|---|
| Good recovery (mRS 0-2) | 480/1054 (46%) | 525/1050 (50%) | p=0.004 |
| Time to first mobilisation | 4.8 hours earlier than UC | Reference group | p<0.0001 |
| Daily mobilisation sessions | 3 additional sessions per day | Reference group | p<0.0001 |
| Quality of life at 12 months | No significant difference | No significant difference | Not significant |
| Serious adverse events | No significant difference | No significant difference | Not significant |
The intervention successfully achieved its protocol targets—VEM patients mobilised significantly earlier and more frequently than UC patients 1 . However, this more intensive approach did not translate into better outcomes and, in fact, appeared to reduce the likelihood of a favorable recovery 1 .
A particularly insightful aspect of the AVERT analysis came from the dose-response examination. Researchers found a complex relationship between the pattern of mobilisation and patient outcomes 1 .
Increased daily frequency of out-of-bed sessions was associated with improved odds of efficacy and safety outcomes 1
Increased amount of mobilisation (minutes per day) was associated with reduced odds of favorable outcomes 1
This suggested that shorter, more frequent mobilisation sessions early after stroke might be more beneficial than longer, less frequent sessions 1 .
| Characteristic | Very Early Mobilisation (VEM) Group | Usual Care (UC) Group |
|---|---|---|
| Total participants | 1054 | 1050 |
| Region (UK/Australasia) | 610/1494 (total) | 610/1494 (total) |
| Age | Comparable between groups | Comparable between groups |
| Stroke type (infarct/hemorrhage) | Comparable between groups | Comparable between groups |
| Stroke severity (NIHSS) | Balanced across mild, moderate, severe | Balanced across mild, moderate, severe |
| Premorbid disability | Comparable between groups | Comparable between groups |
The AVERT findings forced a fundamental rethinking of early stroke rehabilitation practices. The trial demonstrated that the prevailing "more is better" and "sooner is better" approach required refinement 1 .
As a result of these findings, the researchers proposed a new trial—AVERT-DOSE—designed to determine the optimal frequency and dose of early mobilisation 1 .
The AVERT trial also highlighted several challenges in conducting long-term rehabilitation research. The investigators noted that usual care clinicians had started mobilising patients earlier each year during the trial period, subtly altering the context of the comparison 1 . This reflects the evolving nature of clinical practice and the importance of ongoing research.
As research continues, with new approaches like brain stimulation, stem cell therapy, virtual reality, and even drug-enhanced recovery entering the landscape, the lessons from AVERT remain fundamental 5 . In medicine, even our most cherished assumptions must be tested, and sometimes the interventions we believe are helping may need to be rethought in light of new evidence.
The AVERT trial represents a landmark in stroke rehabilitation research—not only for its scale and methodological rigor but for its willingness to challenge established practices. By demonstrating that very early, high-dose mobilisation could actually reduce the odds of a favorable recovery, the study prompted clinicians worldwide to reconsider their approach to early stroke care.
What makes the AVERT story particularly compelling is that it showcases science at its best: questioning assumptions, rigorously testing hypotheses, and following the evidence even when it leads to unexpected places. The trial didn't just answer questions—it opened up new ones, steering the field toward more nuanced investigations of what constitutes optimal rehabilitation.
The future of stroke rehabilitation will likely be more personalized, more precise, and more evidence-based than ever before—thanks in large part to the paradigm-shifting findings of the AVERT trial.