Early mobilization after stroke What do we know (so far)?

Transcription

1 NICIS Neurosciences in Critical Care International Symposium 19 th June, 2015 Early mobilization after stroke What do we know (so far)? Peter Langhorne, Professor of stroke care, Glasgow University

2 Acknowledgements Many thanks to Julie Bernhardt and colleagues at Florey Neurosciences Institutes, Melbourne Australia PL was AVERT investigator and grant-holder Slides provided by; Julie Bernhardt (Melbourne) Terry Quinn (Glasgow)

3 Stroke patients should be mobilised early.

4 Stroke patients should be mobilised early. Early mobilisation is recommended to prevent complications Early mobilization, should be considered for (acute stroke) patients Rehabilitation should start as early as possible once medical stability is reached Patients should be mobilised as early and frequently as possible

5 Stroke patients should be mobilised early. Early mobilisation is recommended to prevent complications Early mobilization, should be considered for (acute stroke) patients No Grade 1A evidence Rehabilitation should start as early as possible once medical stability is reached Patients should be mobilised as early and frequently as possible

6 Limited evidence for individual components of stroke unit care Langhorne et al Lancet Neurol (2012)

7 Early physical and occupational therapy in mechanically ventilated, critically ill patients results in better outcomes Shorter time to achieve mobility milestones Shorter time to achieve independence Schweickert et al. Lancet 2009

8 Stroke Basic science and small trials have been inconclusive Stroke models may help our understanding? Translation research pipeline Very early forced use may be harmful? Jones & Schallert (1994) VECTORS trial Neurology, 2009 Early & higher intensity voluntary exercise improves brain reorganisation & function Teasell et al, Top Stroke Rehab (2005); Janssen (2010) IJS

9 The phasing of AVERT early rehabilitation trial Walk Stand 7% 6% In bed no activity 28% Sit supported 28% Tests 6% In bed talk / eat 25% Modelling Phase 1 Intervention Outcomes Exploratory Trial Phase II Feasibility (safety) Defining intervention Definitive RCT Phase III Fully defined/ measured intervention Does it work?

10 What is Very Early Mobilisation (VEM)? Protocol developed by the AVERT research team. Based on treatment provided in stroke unit in Trondheim, Norway Interventions provided by a nurse /physiotherapist team Protocol/training provided to staff Provided increased mobilisations (tailored impairment)

11 AVERT phase III multicentre RCT Very early mobilisation (VEM) delivered by a physiotherapy /nurse team will result in : 1. Very early (<24h), frequent, higher dose out of bed mobilisations 2. Fewer deaths & less disability at 3 months 3. Fewer complications at 3 months post stroke 4. Better quality of life at 12 months 5. Better cost effectiveness When compared to standard care

12 2104 participants recruited 56 centres (8 countries) Complete follow up 2083 (99%)

13 Sample size, n=2104 Trial pathway Very Early Mobilisation + Usual Care 3+ additional sessions out of bed activity Arrive hospital, screened, recruited < 24 hrs First intervention, < 24 hrs PT /Nurse team, 6 days/wk Stroke Day 14 Treatment ceases 3 month Ax 1 o outcome 12 month Ax Stratified by stroke severity & site Usual stroke unit care 1 o Efficacy endpoint Favourable outcome (mrs 0-2) Safety outcomes: death, SAEs, immobility, neurological

14 Well balanced baseline characteristics 26% patients over 80 years 45% patients mod-severe stroke (NIHSS>7) 12% patients ICH VEM (n=1054) Usual care (n=1050) Australia/New Zealand 617 (59%) 626 (60%) Asia 126 (12%) 125 (12%) UK 311 (29%) 299 (28%) Patient Details Age (Median, IQR) 72 3 (62 3, 80 3) 72 7 (63 4, 80 4) Female 411 (39%) 407 (39%) Risk Factors Hypertension 707 (67%) 717 (68%) Ischaemic Heart Disease 235 (22%) 251 (24%) Diabetes mellitus 239 (23%) 228 (21%) Smoker 227 (22%) 204 (19%) Atrial Fibrillation 229 (22%) 237 (23%) Home at time of admission 1038 (99%) 1036 (99%) Time to randomisation (hours) Median (IQR) 18 2 ( ) 18 2 ( ) Stroke history First Stroke 878 (83%) 843 (80%) NIHSS Score, Median (IQR) 7 (4 12) 7 (4 12) Mild (1 7) 592 (56%) 578 (55%) Moderate (8 16) 315 (30%) 328 (31%) Severe (> 16) 147 (14%) 144 (14%) Stroke type (Oxfordshire) TACI 224 (21%) 232 (22%) PACI 340 (32%) 328 (31%) POCI 93 (9%) 106 (10%) LACI 255 (24%) 268 (26%) ICH 142 (14%) 116 (11%) rtpa treatment, yes 247 (23%) 260 (25%) 24% rtpa

15 Intervention achieved significant differences VEM Usual Care median, IQR n=1054 n=1050 p value median shift (95% CI) Time to first mobilisation (hrs) 18 5 ( ) 22 4 ( ) < ( ) Frequency per person (median daily sessions of out of bed activity) Daily amount per person* (median minutes per day spent in out of bed activity) n=1042; missing=12 n=1036; missing= ( ) 3 ( ) < (3 3 5) 31 ( ) 10 (0 18) < ( ) Total amount per person (mins over the intervention period) ( ) 70 (32 130) < ( ) 75% of all patients started out of bed activity <24 hours

16 Intervention achieved significant differences VEM Usual Care median, IQR n=1054 n=1050 p value median shift (95% CI) Time to first mobilisation (hrs) 18 5 ( ) 22 4 ( ) < ( ) Frequency per person (median daily sessions of out of bed activity) Daily amount per person* (median minutes per day spent in out of bed activity) n=1042; missing=12 n=1036; missing= ( ) 3 ( ) < (3 3 5) 31 ( ) 10 (0 18) < ( ) Total amount per person (mins over the intervention period) ( ) 70 (32 130) < ( )

17 Primary outcome - independence (mrs 0-2) mrs=0 mrs=1 mrs=2 mrs=3 mrs=4 mrs=5 mrs=6 Independent VEM VEM 8,7 46% 19,3 18, Usual care Usual care 9,2 50% 19,5 21, OR 0.73, 95% CI , P=0.004

18 Outcome by subgroup (mrs 0-2) Subgroup Age < No. n pts OR exp(b) (95% CI) 0.74 (0.49, 1.11) 0.70 (0.52, 0.96) > (0.50, 1.14) Effect consistent across all subgroups No significant treatment by group interactions p>0.05 (no additional hazard with rtpa treatment) Stroke Severity Mild 1157 Mod 635 Severe 291 Stroke Type Infarct 1828 Haemorrhage 255 rtpa treated No 1580 Yes 503 Time to first mobilisation <12h h 1194 >24h 515 Recruitment Region ASIA 244 AUST/NZ 1238 UK 601 No significant difference in: 0.75 (0.57, 0.98) 0.76 (0.53, 1.08) 0.35 (0.11, 1.18) 0.77 (0.62, 0.97) Deaths Walking recovery Complications Adverse events 0.48 (0.25, 0.92) 0.74 (0.58, 0.94) 0.71 (0.46, 1.09) 1.02 (0.62, 1.68) 0.56 (0.42, 0.75) 0.78 (0.42, 1.43) 0.74 (0.40, 1.35) 0.73 (0.55, 0.96) 0.74 (0.51, 1.08).125 Favours Usual UCcare Favours Favours VEM VEM

19 Conclusions (1) 1. Meeting protocol is a key challenge in rehabilitation trial We achieved a significant difference in the frequency, amount and timing of rehabilitation 2. The very early, higher dose out of bed activity protocol reduced the odds of favourable outcome, without accelerating walking recovery or reducing immobility-related SAEs more is better may not apply in the first few days after stroke Treatment dose versus benefits/harms warrants further exploration

20 Unpublished data

21 Bernhardt IJS 2015 SAP So how do we unpack this? Prespecified dose response analysis all patients, no group Key intervention criteria: 1) Time to first mobilisation (hours after stroke onset) 2) Frequency, median sessions per day (nurse, PT data) 3) Amount activity out of bed, median minutes per day (PT only) Regression models: eg. Efficacy 3 dose characteristics as independent variables, 3 months mrs outcome (dichotomized mrs 0-2 favourable outcome vs mrs 3-6 as poor outcome) as the dependent variable, adjusted for baseline NIHSS and age Classification and regression tree CART analyses

22 Conclusions (2) 1. The high quality data in this international trial provides the best opportunity yet to determine the best pattern of rehabilitation. 2. Better outcomes seen with short, frequent mobilisations in the early phase after stroke (more likely to regain independence) 3. We need to characterise the optimal patterns of mobilisation for these patients Further exploration will help underpin clinical practice guidelines Watch this space

23 Thank you for your attention