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

Julie Bernhardt; Leonid Churilov; Fiona Ellery; Janice Collier; Jan Chamberlain; Peter Langhorne; Richard I Lindley; Marj Moodie; Helen Dewey; Amanda G Thrift; Geoff Donnan; AVERT Collaboration Group

doi:10.1212/WNL.0000000000002459

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

Neurology. 2016 Jun 7;86(23):2138-45. doi: 10.1212/WNL.0000000000002459. Epub 2016 Feb 17.

Collaborators

AVERT Collaboration Group:
Julie Bernhardt, Leonid Churilov, Janice Collier, Helen Dewey, Geoffrey Donnan, Fiona Ellery, Peter Langhorne, Richard Lindley, Marjory Moodie, Brooke Parsons, Amanda Thrift, Geoffrey Donnan, Helen Dewey, Julie Bernhardt, Peter Langhorne, Marjory Moodie, Brooke Parsons, Main Investigators MIs, Bent Indredavik, Torunn Askim, Phillip Bath, Christopher Bladin, Christopher Reid, Stephen Read, Cathy Said, Sandy Middleton, Judith Frayne, Velandai Srikanth, Australia Julie Bernhardt, Helen Dewey, Julie Bernhardt, Geoffrey Donnan, Amanda Thrift, Robert Carter, Richard Lindley, Julie Bernhardt, Geoff Donnan, Richard Lindley, Amanda Thrift, Peter Langhorne, Marjory Moodie, Helen Dewey, Leonid Churilov, Peter Langhorne, Peter Langhorne, Olivia Wu, Julie Bernhardt, Matthew Walters Claire Ritchie, Lorraine Smith, Peter Langhorne, Olivia Wu, Anne Ashburn, Helen Rodgers, Julie Bernhardt, Peter Langhorne, Anne Ashburn, Julie Bernhardt, Helen Rogers, Olivia Wu, Sheila Lennon, Sheila Lennon, Michael Power, Julie Bernhardt, Shahul Hameed, Shahul Hameed, Ratnagopal Pavanni, Peter Lim, Julie Bernhardt, Dawn Tan, Leonid Churilov, Tim Brewer, Janice Collier, Nick Haritos, Edwin Leong, Cecilia Li, Caesar NayWin, Marcus Nicol, Liudmyla Olenka, Li Chun Quang, Marjory Moodie, Robert Carter, Silvia Hope, Lauren Sheppard, Kiusiang Tay- Teo, Olivia Wu, Toby Cumming, Thomas Linden, Karen Borschmann, Jan Chamberlain, Janice Collier, Toby Cumming, Fiona Ellery, Teresa Occhiodoro, Helen Palfreeman, Tara Purvis, Bernadette Sirgo, Nick Tiliacos, John Van Holsteyn, Henry Zhao, Beverly Armstrong, Louise Craig, Fiona Graham, Lynn Legg, Rosemary Morrison, Heather Moorhead, Lorraine O'Donohue, Susan Rogers, Myra Smith, Denise Forshaw, Jane Fitzgerald, E Hibbert, R Melling, S Petrolo, T Purvis, H Williamson MIs, P Adams, L Augoustakis, S Batcheler, S Berney, V Cobani, B Cohen, H Dewey, S Gangi, N Giofre, C Gordon, L Hegarty, M Hindson, F Horvath, S Kalinowski, A Kleine, S Kramer, J Lawrence, S Lindquist, N Logan, A Macdonell, J Matlioski, N McDonough, S McLennan, M McNamee, L Miller, C Nall, E Nelson, K Ng, Z Nicholas, C Nunn, K Owen, E Plant, L Proud, D Quah, K Rodway, S Sertori, V Sheldon, L Sherry, S Speare, K Stansfeld, N Studden, Z Teoh, L Twist, G Velupillai, L Walker, K Wall, A Warwick, R Wharrie, J Wilson, H Worboys, D Young, J Ancliffe Mi, M Bryant, B Doran, M Field, P Fogliani, A Haber, G Hankey, D Hendrie, V Jackaman, A Jacobsen, S Jose, R Lim, R Louis, S Nanthakumar, S Pain, A Power, B Rappeport, J Reynolds, L Smith, S Tombe, A Wesseldine, T West, K Clarke, H Maccanti, L Marr, S Plumb, J Quiney, L Werner MIs, E Abeykoon, W Apirutvorrachod, L Attard, S Behanan, D Brown, K Buchanan, D Butler, M Camac, S Davis, D Diocera, N Gan, C Gendre, J Germaine, P Hand, L Maurenbrecher, J McCulloch, S Mcritchie, M Ong, R Pachett, L Pesavento, H Power, R Reilly, M Sawers, G Silva, C Stevens, L Taylor, T Timms, M Ugalde, A Vardy, J Wallace, S Walsh, E Whatley, E Winter, M Baxter, M Davis, L Sundararajan MIs, E Butler, K Caspers, E Coulter, S Shaw, F Kent, H Lack, F Leavold, J Lord, J Martin-Francisco, R Mohanraj, R Nelson, T O'Neill, R Otto, J Parker, V Rees, B Stevens, R Chen Mi, Ri Lindley, J Bindra, R Dongre, N Downey, M Ferris, L Gibson, R Gonzalez, M Kinniburgh, M Lazaridou, D McCormack, R Singh, A Stepney, Y Tria, K Bainbridge, B Killey, R Sheedy MIs, O Aitchison, L Bray, K Clatworthy, S Coghill, M Collins, L Cornwall, J Dow, P Gates, S Gillett, N Johnson, S Joseph, K Kopelke, R Lam, R Levy, N Lloyd, S Logan, G McPherson, M Newth, C Parsons, K Powles, M Rebis, T Samakowidic, L Sanders, S Savickas, J Shrimpton, H Smith, L Smith, J Spehr, J Summers, G Taylor, M Thackeray, B Wilkinson, K Richardson Mi, J Frayne, E Barber, L Bode, A Brakey, K Chand, P Christin, G Crook, D Delrosario-Kelly, R Descallar, A Deutsch, S Easo, M Farquhar, P Fergus, J Ford, E Hamson, M Hlaing, E Hope, J Lacivita, J Laurenson, K Lock, N Ly, K McKay, C Mill, K Moloney, L Price, T Terry, A Tyers, S Willems, R Woolstencroft, N Crawshaw, J Luker, C Wood, S Choat MIs, C Archer, D Benham, M Billinger, M Bronca, S Curchin, C Dickie, M Dixon, D Douglass, M Enomoto, K Ernst, L Fries, S George, E Green, L Hamilton, Z Harris, T Heard, G Hunt, N Jamieson, M Mackenzie, H McKearney, B Oermann, C O'Reilly, T Pearson, N Reid, L Rodda, D Scutcheon, C Simons, R Smith, L Tait, J Troake, D Usher, L Mackey, T Wijeratne MIs, C Abela, S Ashoka, C Chen, T Cheng, V Chong, S Cooke, A Fok, L Galang, C Grant, S Karageorge, K Kat, L Keo, B Lee, A Luscombe, J Mackay, M Minett, J Mizen, P Nim, N Nunlist, V Patel, M Pathirage, A Paton, M Pombuena, N Rathnayake, L Rhodes, M Sequeira, S Smart, S Somaratne, N Sta Maria, L Talbot, R Tecle, M Shannon, R Gerraty MIs, S Allen, R Boyle, N Fatchen, N Hendley, A Hyde, M Inal, P Kalubowilage, M Laverde, K Lawless, A McFadyen, K Peters, C Pugh, C Qin, J Robertson, S Smee, R Tomlinson, V Wang, F Williams, D Woolley, R Yawieriin, N Austin, S Pomfret, M Tinsley MIs, L Allport, C Ang, L Armitage, E Blundell, A Courtney, M Dela Costa, T Devi Thapa, P Diwakar, M Dulleh, J Francis, P Cic, G Gellie, C Gill, D James, S Lee, T Mai, K Majcher, C Mawson, G Newton, N Qiu, E Ragonton, L Roberts, H Saitamis, L Stanwell, L Ting, P Xu, L Yin, V Crosby Mi, K Broadhead, J Church, R Collins, K Everitt, M Fisher, K Hochmuth, N Jones, A Lieschke, E McCarthy, C McGlone, D Morey, D Neilson, S Spry, M Vile, R Grimley, D Rowley MIs, I Rosbergen, E Ahern, L Anderson, J Boreham, R Devin, R Doolan, M Dyke, L Griffiths, K Guest, D Hecita, N Kendal, J Koltermann, M Lacy, S Lebeter, D Lloyd, M Matthews, C McAuley, A Pollock, M Pyke, T Rogers, S Street, G Styles, A Tampiyappa, J Trinder, T Verral, K Walker, C White, T Beckwith, L Cormack MIs, J Arriagada, C Babenschneider, D Blacker, S Bennett, S Connor, J Cowmeadow, N Daniel, G Edmonds, M Faulkner, M Garcia-Vega, K Kruger, B Martial, P McGinley, H Mountford, V Riley, N Smith, F Stepan, S Tilley, S Whisson, P Groot Mi, J Bailey, K Ballinger, C Bell, B Camilleri, C Charnley, D Crabbe, S Crossland, N Edirimanna, C Fitzgerald, C Gibbins, J Gibbs, K Hirst, A Kennedy, E Klose, K McDowall, S Miller, R Morgan, A Noonan, M North, M Oliver, K Richards, T Russell, N Scott, A Shlanski, A Traynor, S Smith Mi, R Adams, C Banks, K Burke, S Hewat, B McKenna, M McKimmie, L Polmear, M Traumanis, S Whiteman, V Bramah, R Errey, M Halpin, V Molan, D Wheelwright, N Wilson, W Zhang MIs, M Bakshi, S Bracher, M Bryant, W Byrnes, T Denton, N DeVries, P Fay, P Galbraith, T Gallaher, O Haidar, K Holgate, K Hozack, N Jackson, S Kipps, S Lerner, R Markus, R Merheb, C Naismith, G Nolan, R Odelli, K Page, P Sangvatanakul, T Simpson, P van Vliet, K Walch, S Walker, T Yasue, G Auld Mi, R Baker, K Cousins, M Fairbrother, K Hutchinson, M Maclean, E Maher, D Mills, S Ohlback, J Sturm, M Tooth, J Watkins, J Cramb Mi, P Atkinson, J Conrad, D Fichera, S Follent, C Gilbert, M Herzig, S Kohler, S McCracken, L Nunan, S Roberts, J Shelley, S Varendorff, A Wills, A Moore, A Robertson MIs, J Britton, A Burgess, T Coates, J Croft, E Greening, J Holland, P O'Brien, R Strong, L Tighe Mi, S Bilston, J Black, K De Rivera, I Dwyer, S Gissane, K Heckenberg, S Jackson, A Maclagan, L O'Hare, H Patel, J Pearce, C Scanlan, K Seymour, M Symington, A Tyers, A Waite, K Wiesner, O Katalinic, M Spear MIs, P Brown, E Difuntorum, S Gilbert, J Henderson, D James, H Janssen, E Lane, S Lowndes, D Smith, S Thompson, D Weaver, S Weston, S Wright, S Cox, C Tse MIs, J Adrian, M Doughty, J Kok, R McGrath, T Morris, A Pickup, E Ray, R Richardson, M Sims, C Thompson, K Trinh, N Walton, F Whittaker, P Andersen Mi, J Burrows, M Dawson, D Griffiths, G Harris, P Kavalieros, B O'Brien, K Roberts, J Watkins, C Whyatt, A McRae, G Wavish MIs, F Anos, J Armstrong, E Au, A Barber, C Bates, M Bertulfo, A Boggs, F Burgess, K Cassels-Brown, M Chiu, S Dass, N Duff, J Farrell, W Foster, D Fuertez, C Gadhvi, S George, A Green, L Harvey-Fitzgerald, L Hau, L Hayward, D Holman, K Huggins, M Jacobs, A John, H Kaur, T Lagerstedt, J Lee, R Llenes, L Lyons, S Magandi, M Martin, S Mathew, T Mathew, D McKellar, E Moss, Kl Nand, K Nicol, F Peterson, A Prasad, K Quick, E Revell, S Roy, J Ryan, N Samadi, B Scrivener, J Slow, S Tharakan, J Torrens, E van Bysterveldt, C Villaluz, S Yang, Ma Katijjahbe, G Ai Sing, A Azlina, Mi Azmi, Mh Efri, Az Fadilah, H Fathuddeen, H Haryani, H Hussien, M Izuani, Zc Man, C Man Ying, Km Mashitoh, A Noor Azah, Mi Norlinah, I Norliza, Kb Ravinder, R Rohaizah, K Rosnita, A Rozita, J Safwan, R Sahathevan, I Shahrul, Sm Sharifah, Hj Tan, Wy Wan Nafisah, Yl Yee, Ma Zaharah, As Zunaidah, D Tan, Mt Ahmad, S Hameed MIs, Mfb Bakari, J Britto, Jj Chen, S Choo, M Faizal, Fk Fong, S Hong, J Ja'afar, Z Ke, G Koh, Ck Lee, Yf Lee, P Lim, Gm Lim, Sh Ninhadi, G Ong, T Pei Pei, V Penero, N Rahim, P Ratnagopal, K Saleh, Hc Seow, E Sim, Ck Tan, Py Tay, I Teo, S Thilarajah, Phj Wong, Wp Wong, S Yeap, M Macleod Mi, A Anderson, K Armstrong, K Baird, D Balfour, M Boyd, J Cameron, C Carswell, C Clanachan, L Cuthill, I Devoy, S Forsyth, J Gavin, M Hughes, E Marr, S McAuley, E McCagherty, K McCallum, N McDonald, C McGhee, Ta McIntyre, L Noonan, A Smart, R Walshe, D Neal Mi, J Allison, G Ball, S Board, H Brunt, C Buckley, C Carroll, D Hayward, T Hutchinson, E Jones, E Keeling, E Marsh, N Mead, H Smith, C Vickers, B Williams-Yesson, D Wood, J Coyle, M Keeling MIs, L Ackroyd, C Brown, K Donnan, N Dyer, H Green, G Kilbride, C Nicholson, M Porteous, S Louw Mi, A Annamalai, A Barkat, S Crawford, M Fawcett, D Harvey, V Hogg, A Hughes, J Kemp, J Morrison, K Storey, T Thompson, J Furnace, Mj Macleod MIs, J Bell, K Bennett, M Bruce, R Clarke, H Cowie, H Gow, J Irvine, A Joyson, S MacDonald, A Macvicar, N Murphy, J Robertson, C Gordon, J Kwan, L Redpath, K Saunders MIs, J Bell, R Burrow, C Clarke, C Dickson, G Hann, M Heath, S Heath, A Hewett, R Humphrey, B Longland, A Orpen, C Ovington, J Page, E Rogers, K Toombs, R Howes, A Lacey, P Meakin MIs, D Ames, S Banerjee, E Beranova, S Berry, Mj Burke, V Cassama, K Collins, J Crow, A Dunne, C Gomez, A Hawkins, K Hellier, Sa Howard, A Kar, E Lambert, H Lee, C Mandri, J Moye, E Murtagh, J Pushpa-Rajah, J Richardson, TSachs, J Stilwell, V Tilley, P Wilding, N Wilson, E Feely, S Kirk MIs, P Cassidy, A Chalmers, C Duguid, N Hughes, J Hutton, K Lapsley, J Lee, A Murray, L Weir, M Whitelaw, M Barber, D Esson MIs, H Armit, C Devlin, R Duncan, C Forman, K Frame, L Hogg, P McLeod, R McWhinney, J Porter, M Purves, L Snowball, B Wroath Mi, L Ferson, M Gibson, S Gillespie, N Ignatius, T Kane, J Kwant, M Matthews, C McCallion, C McConville, M McDowell, C McNally, L Moore, P Murphy, A Nesbitt, J Newell, M Power, E Reid, K Robinson, C Charnley, M James MIs, S Bacon, N Booth, A Bowring, L Boxall, J Burt, J Cageao, N Green, K Gupwell, S Keenan, H Kingwell, M Kryszkowska, J Mortimore, B Peace, C Roughan, G Gunathilagan, J Sampson, G Thomas MIs, T Allen, G Dane, K Harris, S Hart, Sa Jones, M Reader, P Browne, C McGoldrick, D Mullan MIs, P Adair, J Armstrong, E Beggs, I Bell, C Edwards, L Gilligan, C Kelly, M Kennedy, J Kurian, L Leal, A McAtamney, E McKay, E Rogan, M Smyth, E Wiseman, J Vahidassr, C Price, V Riddell MIs, E Bendix, K Craig, R Davison, A Harrison, A Smith, V Green Mi, K Ashton, W Barkhuizen, A Daniel, C Dickinson, H Durdu, D Eastwood, H Goddard, R Hodkin, J Howard, C Jeffs, S Joyce, C Kelly, G Kerr, J Lanes, B Magnall, M McMahon, M Moody, S Patton, R Taylor, A Watson, K Mitchelson, L Mokoena MIs, L Aird, R Lakey, J Murdy, K Nelson, G Storey, R McGeown, S Tauro MIs, R Brady, D Holland, M Kinnaird, L Maltman, D Martin, K McCord, S McKenna, C Morgan, C Shannon, A Steele, I Wiggam, S Appleby, S Brotheridge, M Prescott MIs, P Bagot, D Baston, C Bennett, J Featherstone, C Hare, A McCluskey, S Wade, R Worton, E Hakim, J Herman, T Norman MIs, L Beale, E Buckley, K Byrne, M Gasior, B Robles, C Smallwood, S Stevens, M Thomas, V Williams, K Buck Mi, S Armstrong, V Brice, A Edwards, S Gething, A Griffiths, T Hills, D Howells, S Langdon, S Moseley, G Powell, G Reynolds, B Richard, E Scott, R White, J Zebedee, M Walters Mi, J Alexander, L Brand, E Colquhoun, A Hill, D Macartney, H MacDonald, B Manak, H Morgan, C Ritchie, H Hunter Mi, T Blair, M Duffy, J Graham, J Scott, T Vu, P Yorston, A Nair Mi, I Shakir, C Button, M Friend, J Greig, B Hairsine, S Wade, S Williamson, G Cloud Mi, T Adedoyin, N Dayal, S Gawned, R Ghatala, N Jeyaraj, L Kerin, L Montague, C Orefo, J O'Reilly, J Styles, S Trippier, C Watchurst, F Watson, J Hunt, R Latif MIs, C Barrett, J Cox, F Hammonds, K Quick, K Robinson, A Skinner, C Vernon, S Burgess, T Elder-Gracie MIs, C Browne, W Cameron, V Coleman, C Fulgencio, L Gibson, P Halliday, D Heaney, L Main, K McGavin, G Mead, F Proudfoot, A Redpath, C Rodger, S Scott, K Robinson, K Mason Mi, L Baxter, A Bryce, M Halkett, J Halliday, A McAllister, M McGuiness, M Munro, A Robb, A Thompson, B Tougher, J Weadon, J Young, C Douglas Mi, M McParland, S Boyle, B Byrne, L Comiskey, J Gilpin, S Gilpin, A Harris, S Harshaw, J Haughey, F McArdle, L McConnell, E McEneaney, M Millar, M Murphy, J Tilley

Affiliations

¹ From The Florey Institute of Neuroscience and Mental Health (J.B., L.C., F.E., J. Collier, J. Chamberlain, H.D., G.D.), La Trobe University (J.B.), Melbourne, Australia; Institute of Cardiovascular and Medical Sciences (P.L.), University of Glasgow, UK; George Institute for Global Health and Westmead Hospital Clinical School (R.I.L.), University of Sydney; Deakin Health Economics (M.M.), Faculty of Health, Deakin University, Burwood; and Eastern Health Clinical School, Faculty of Medicine, Nursing and Health Sciences (H.D.), and Stroke and Ageing Research Group, Department of Medicine, School of Clinical Sciences at Monash Health (A.G.T.), Monash University, Clayton, Australia. julie.bernhardt@florey.edu.au.
² From The Florey Institute of Neuroscience and Mental Health (J.B., L.C., F.E., J. Collier, J. Chamberlain, H.D., G.D.), La Trobe University (J.B.), Melbourne, Australia; Institute of Cardiovascular and Medical Sciences (P.L.), University of Glasgow, UK; George Institute for Global Health and Westmead Hospital Clinical School (R.I.L.), University of Sydney; Deakin Health Economics (M.M.), Faculty of Health, Deakin University, Burwood; and Eastern Health Clinical School, Faculty of Medicine, Nursing and Health Sciences (H.D.), and Stroke and Ageing Research Group, Department of Medicine, School of Clinical Sciences at Monash Health (A.G.T.), Monash University, Clayton, Australia.

Abstract

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.

Publication types

Multicenter Study
Pragmatic Clinical Trial

MeSH terms

Age Factors
Aged
Aged, 80 and over
Brain Ischemia / mortality
Brain Ischemia / rehabilitation
Cerebral Hemorrhage / mortality
Cerebral Hemorrhage / rehabilitation
Disability Evaluation
Early Ambulation / adverse effects
Early Ambulation / methods*
Female
Humans
Male
Middle Aged
Odds Ratio
Recovery of Function
Severity of Illness Index
Stroke / mortality
Stroke Rehabilitation / adverse effects
Stroke Rehabilitation / methods*
Time Factors
Treatment Outcome

Grants and funding

12/01/16/DH_/Department of Health/United Kingdom