Julie Bernhardt1,2, Karen Borschmann3,2, Janice M Collier3, Amanda G Thrift4, Peter Langhorne5, Sandy Middleton6, Richard I Lindley7, Helen M Dewey3,8, Philip Bath9,10, Catherine M Said11,12, Leonid Churilov13,2,14, Fiona Ellery3, Christopher Bladin15,16, Christopher M Reid17,18, Judith H Frayne19,20, Velandai Srikanth21, Stephen J Read22, Geoffrey A Donnan23,2. 1. Stroke Theme, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, Australia julie.bernhardt@florey.edu.au. 2. NHMRC Centre for Research Excellence in Stroke Rehabilitation and Brain Recovery, Melbourne, Australia. 3. Stroke Theme, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, Australia. 4. Stroke and Ageing Research, Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Australia. 5. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK. 6. Nursing Research Institute, St Vincent's Health Australia, Sydney and Australian Catholic University, Darlinghurst, Australia. 7. Westmead Clinical School, University of Sydney, Australia. 8. Eastern Health Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia. 9. Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, Nottingham, UK. 10. Stroke, Nottingham University Hospitals NHS Trust, Nottingham, UK. 11. Physiotherapy, University of Melbourne, Parkville, Australia. 12. Physiotherapy, Western Health, St Albans, Australia. 13. Department of Medicine Austin Health, University of Melbourne, Heidelberg, Australia. 14. School of Sciences, RMIT University, Melbourne, Australia. 15. Ambulance Victoria, Florey Institute of Neuroscience and Mental Health, Heidelberg, Australia. 16. Eastern Health Clinical School, Monash University, Box Hill, Australia. 17. School of Public Health, Curtin University, Perth. 18. CCRE Therapeutics, Monash University, Melbourne, Australia. 19. Alfred Hospital, Melbourne, Australia. 20. Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia. 21. Peninsula Health & Peninsula Clinical School, Monash University, Melbourne, Australia. 22. Faculty of Medicine, The University of Queensland, Herston, Australia. 23. University of Melbourne, Melbourne Brain Centre, Parkville, Australia.
Abstract
OBJECTIVE: This tertiary analysis from AVERT examined fatal and non-fatal Serious Adverse Events (SAEs) at 14 days. METHOD: AVERT was a prospective, parallel group, assessor blinded, randomized international clinical trial comparing mobility training commenced <24 hours post stroke, termed very early mobilization (VEM) to usual care (UC). Primary outcome was assessed at 3 months. Included: Patients with ischaemic and haemorrhagic stroke within 24 hours of onset. Treatment with thrombolytics allowed. Excluded: Patients with severe premorbid disability and/or comorbidities. Interventions continued for 14 days or hospital discharge if less. The primary early safety outcome was fatal SAEs within 14 days. Secondary outcomes were non-fatal SAEs classified as neurologic, immobility-related, and other. Mortality influences were assessed using binary logistic regression adjusted for baseline stroke severity (NIHSS) and age. RESULTS: 2,104 participants were randomized to VEM (n = 1,054) or UC (n = 1,050) with a median age of 72 years (IQR 63-80) and NIHSS 7 (IQR 4-12). By 14 days, 48 had died in VEM, 32 in UC, age and stroke severity adjusted Odds Ratio of 1.76 (95% CI 1.06-2.92, p = 0.029). Stroke progression was more common in VEM. Exploratory subgroup analyses showed higher odds of death in intracerebral haemorrhage and >80 years subgroups, but there was no significant treatment by subgroup interaction. No difference in non-fatal SAEs found. CONCLUSION: While the overall case fatality at 14 days post-stroke was only 3.8%, mortality adjusted for age and stroke severity was increased with high dose, intensive training compared to usual care. Stroke progression was more common in VEM. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that very early mobilization increases mortality at 14 days post stroke. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12606000185561.
OBJECTIVE: This tertiary analysis from AVERT examined fatal and non-fatal Serious Adverse Events (SAEs) at 14 days. METHOD: AVERT was a prospective, parallel group, assessor blinded, randomized international clinical trial comparing mobility training commenced <24 hours post stroke, termed very early mobilization (VEM) to usual care (UC). Primary outcome was assessed at 3 months. Included: Patients with ischaemic and haemorrhagic stroke within 24 hours of onset. Treatment with thrombolytics allowed. Excluded: Patients with severe premorbid disability and/or comorbidities. Interventions continued for 14 days or hospital discharge if less. The primary early safety outcome was fatal SAEs within 14 days. Secondary outcomes were non-fatal SAEs classified as neurologic, immobility-related, and other. Mortality influences were assessed using binary logistic regression adjusted for baseline stroke severity (NIHSS) and age. RESULTS: 2,104 participants were randomized to VEM (n = 1,054) or UC (n = 1,050) with a median age of 72 years (IQR 63-80) and NIHSS 7 (IQR 4-12). By 14 days, 48 had died in VEM, 32 in UC, age and stroke severity adjusted Odds Ratio of 1.76 (95% CI 1.06-2.92, p = 0.029). Stroke progression was more common in VEM. Exploratory subgroup analyses showed higher odds of death in intracerebral haemorrhage and >80 years subgroups, but there was no significant treatment by subgroup interaction. No difference in non-fatal SAEs found. CONCLUSION: While the overall case fatality at 14 days post-stroke was only 3.8%, mortality adjusted for age and stroke severity was increased with high dose, intensive training compared to usual care. Stroke progression was more common in VEM. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that very early mobilization increases mortality at 14 days post stroke. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12606000185561.
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