PDF: AVERT
(2015)Objective
To determine whether very early mobilization (within 24h) improves outcomes in acute stroke patients compared to standard care.
Study Summary
• More deaths or dependency in early mobilization group (46% vs 50%, p=0.04)
• Early mobilization led to shorter hospital stays but more frequent and longer activity sessions
Intervention
Multicenter, open-label randomized trial comparing very early mobilization (median 18.5h after stroke) vs standard mobilization (median 22.4h). Intervention included more frequent and longer sessions of sitting, standing, and walking.
Inclusion Criteria
• Ischemic or hemorrhagic stroke
• Within 24h of onset
• Age ≥18
• mRS 0–2 pre-stroke
Study Design
Arms: Very early mobilization vs usual care
Patients per Arm: 1054 early mobilization, 1050 usual care
Outcome
• Median LOS: 10 days (early) vs 11 (usual care)
• Serious adverse events: similar between groups
Bottom Line
VEM within 24h was harmful: functional independence (mRS 0-2) at 3 months was significantly lower with VEM (46% vs 50%; adjusted OR 0.73; 95% CI 0.59-0.90; P=0.004). Dose-response analysis revealed a paradox: more frequent short sessions improved outcomes (OR 1.13/session), but more total daily minutes worsened outcomes (OR 0.94 per 5 min) — suggesting short, frequent mobilizations are preferable to prolonged early sessions.
Major Points
- VEM significantly worsened outcome: 46% vs 50% mRS 0-2 at 3 months (aOR 0.73; 95% CI 0.59-0.90; P=0.004).
- Intervention delivered: VEM patients mobilised 4.8h earlier, 3 more sessions/day, 21 more minutes/day (all P<0.0001). 92% vs 59% mobilised within 24h.
- No significant mortality difference: 8% vs 7% at 3 months (aOR 1.34; 95% CI 0.93-1.93; P=0.113).
- No walking recovery difference: 75% vs 76% walking unassisted by 3 months (P=0.459).
- No QoL difference at 12 months: AQoL 0.47 vs 0.49 (P=0.865).
- Dose-response paradox: frequency improved outcomes (OR 1.13/session; P<0.001) while duration worsened them (OR 0.94/5min; P<0.001).
- ICH subgroup signal: OR 0.48 for favorable outcome, OR 3.21 for death (not significant interaction but concerning).
- Severe stroke patients: VEM only 7% favorable vs UC 35%.
- UC temporal drift: TTFM shortened 28 min/year (P=0.001) over 8-year trial, narrowing group contrast.
- Meta-analysis of 9 RCTs (2,618 patients): early mobilisation showed no benefit — OR 1.10 (0.94-1.29) for death/dependency.
Study Design
- Study Type
- Phase III pragmatic parallel-group randomized controlled trial
- Randomization
- Yes
- Blinding
- Single-blind (blinded outcome assessors). Web-based stratified block randomization (average block size 6), stratified by site and NIHSS (mild 1-7, moderate 8-16, severe >16).
- Sample Size
- 2104
- Follow-up
- Primary: 3 months. Secondary: 12 months.
- Centers
- 56
- Countries
- UK, Australia, New Zealand, Malaysia, Singapore
Primary Outcome
Definition: Favourable outcome (mRS 0-2) at 3 months
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 525/1,045 (50%) | 480/1,038 (46%) | - (0.59-0.90) | 0.004 |
Limitations & Criticisms
- UC contamination: TTFM shortened 28 min/year (P=0.001) over 8-year trial; by end, ~2/3 UC patients mobilised within 24h.
- Complex intervention difficult to standardize across 56 sites.
- Unblinded treating staff could influence outcomes beyond mobilisation (attention, reassurance).
- Physiological monitoring data limited in large pragmatic trial.
- Subgroup interactions underpowered — ICH/severe stroke trends are hypothesis-generating.
- Daily amount measured from physiotherapy only, may underestimate total OOB time.
- Economic analysis not completed.
Citation
Lancet. 2015;386:46-55.