Academic Section of Geriatric Medicine, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
Health Technol Assess. 2017 Sep;21(54):1-120. doi: 10.3310/hta21540.
Mobilising patients early after stroke [early mobilisation (EM)] is thought to contribute to the beneficial effects of stroke unit care but it is poorly defined and lacks direct evidence of benefit.
We assessed the effectiveness of frequent higher dose very early mobilisation (VEM) after stroke.
We conducted a parallel-group, single-blind, prospective randomised controlled trial with blinded end-point assessment using a web-based computer-generated stratified randomisation.
The trial took place in 56 acute stroke units in five countries.
We included adult patients with a first or recurrent stroke who met physiological inclusion criteria.
Patients received either usual stroke unit care (UC) or UC plus VEM commencing within 24 hours of stroke.
The primary outcome was good recovery [modified Rankin scale (mRS) score of 0-2] 3 months after stroke. Secondary outcomes at 3 months were the mRS, time to achieve walking 50 m, serious adverse events, quality of life (QoL) and costs at 12 months. Tertiary outcomes included a dose-response analysis.
Patients, outcome assessors and investigators involved in the trial were blinded to treatment allocation.
We recruited 2104 (UK, = 610; Australasia, = 1494) patients: 1054 allocated to VEM and 1050 to UC. Intervention protocol targets were achieved. Compared with UC, VEM patients mobilised 4.8 hours [95% confidence interval (CI) 4.1 to 5.7 hours; < 0.0001] earlier, with an additional three (95% CI 3.0 to 3.5; < 0.0001) mobilisation sessions per day. Fewer patients in the VEM group ( = 480, 46%) had a favourable outcome than in the UC group ( = 525, 50%) (adjusted odds ratio 0.73, 95% CI 0.59 to 0.90; = 0.004). Results were consistent between Australasian and UK settings. There were no statistically significant differences in secondary outcomes at 3 months and QoL at 12 months. Dose-response analysis found a consistent pattern of an improved odds of efficacy and safety outcomes in association with increased daily frequency of out-of-bed sessions but a reduced odds with an increased amount of mobilisation (minutes per day).
UC clinicians started mobilisation earlier each year altering the context of the trial. Other potential confounding factors included staff patient interaction.
Patients in the VEM group were mobilised earlier and with a higher dose of therapy than those in the UC group, which was already early. This VEM protocol was associated with reduced odds of favourable outcome at 3 months cautioning against very early high-dose mobilisation. At 12 months, health-related QoL was similar regardless of group. Shorter, more frequent mobilisation early after stroke may be associated with a more favourable outcome.
These results informed a new trial proposal [A Very Early Rehabilitation Trial - DOSE (AVERT-DOSE)] aiming to determine the optimal frequency and dose of EM.
The trial is registered with the Australian New Zealand Clinical Trials Registry number ACTRN12606000185561, Current Controlled Trials ISRCTN98129255 and ISRCTN98129255.
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 21, No. 54. See the NIHR Journals Library website for further project information. Funding was also received from the National Health and Medical Research Council Australia, Singapore Health, Chest Heart and Stroke Scotland, Northern Ireland Chest Heart and Stroke, and the Stroke Association. In addition, National Health and Medical Research Council fellowship funding was provided to Julie Bernhardt (1058635), who also received fellowship funding from the Australia Research Council (0991086) and the National Heart Foundation (G04M1571). The Florey Institute of Neuroscience and Mental Health, which hosted the trial, acknowledges the support received from the Victorian Government via the Operational Infrastructure Support Scheme.
人们认为在中风后早期让患者活动（早期活动）有助于发挥卒中单元护理的有益作用，但目前对早期活动的定义不够明确，且缺乏其有益效果的直接证据。
评估卒中后频繁、高剂量早期活动（VEM）的有效性。
这是一项平行组、单盲、前瞻性随机对照试验，使用基于网络的计算机分层随机化进行盲法终点评估。
试验在五个国家的 56 个急性卒中单元进行。
纳入首次或复发性卒中且符合生理纳入标准的成年患者。
患者接受常规卒中单元护理（UC）或 UC 加 VEM，在卒中后 24 小时内开始。
主要结局是卒中后 3 个月时的良好恢复（改良 Rankin 量表评分 0-2）。次要结局为 3 个月时的改良 Rankin 量表评分、达到行走 50 米的时间、严重不良事件、12 个月时的生活质量（QoL）和成本。次要结局包括剂量反应分析。
患者、结局评估者和参与试验的研究人员均对治疗分配不知情。
我们共纳入 2104 例患者（英国，n=610；澳大拉西亚，n=1494）：1054 例分配到 VEM 组，1050 例分配到 UC 组。干预方案的目标均已达成。与 UC 组相比，VEM 组患者更早开始活动（4.8 小时，95%置信区间 4.1-5.7 小时； < 0.0001），每天额外进行 3 次（95%置信区间 3.0-3.5 次； < 0.0001）活动。VEM 组（n=480，46%）的预后良好患者少于 UC 组（n=525，50%）（调整后的优势比 0.73，95%置信区间 0.59-0.90； = 0.004）。澳大拉西亚和英国的结果一致。3 个月时的次要结局和 12 个月时的 QoL 无统计学差异。剂量反应分析发现，随着每日离床活动次数的增加，疗效和安全性结局的优势比呈一致的改善模式，但随着活动时间（分钟/天）的增加，优势比呈下降趋势。
UC 临床医生每年都会更早地开始活动，改变了试验的背景。其他潜在的混杂因素包括工作人员与患者的互动。
VEM 组患者的活动时间更早，治疗剂量更高，而 UC 组本身已经是早期开始活动。与 UC 组相比，VEM 方案与 3 个月时预后不良的风险降低相关，提示早期进行高剂量的活动可能不利。12 个月时，无论组间如何，健康相关 QoL 相似。卒中后早期进行更短、更频繁的活动可能与更有利的结局相关。
这些结果为一项新的试验提案（早期康复试验-剂量（AVERT-DOSE））提供了信息，该提案旨在确定早期活动的最佳频率和剂量。
该试验在澳大利亚和新西兰临床试验注册中心注册，编号为 ACTRN12606000185561、Current Controlled Trials ISRCTN98129255 和 ISRCTN98129255。
该项目由英国国家卫生与保健研究所（NIHR）卫生技术评估计划资助，全文将在 ; Vol. 21, No. 54 发表。请访问 NIHR 期刊图书馆网站获取进一步的项目信息。该项目还得到了澳大利亚新西兰健康与医学研究理事会、新加坡卫生、苏格兰胸心和中风协会、北爱尔兰胸心和中风协会、以及中风协会的资助。此外，Julie Bernhardt（1058635）还获得了澳大利亚研究理事会（0991086）和澳大利亚国家心脏基金会（G04M1571）的奖学金。主办该试验的弗洛里神经科学与心理健康研究所感谢维多利亚州政府通过运营基础设施支持计划提供的支持。
