This was a multicenter, randomized, prospective and parallel-group study on the efficacy and safety of electromechanical -assisted gait trainer Exowalk®. All enrolled subjects were patients with stroke. Three clinical research centers participated in this trial as follows: Dongguk University Ilsan Hospital, Chungnam National University Hospital and Seoul National University Bundang Hospital. This research protocol was approved by each hospital as follows: Dongguk University Ilsan Hospital’s Institutional Review board (IRB No. DUIH 2018-08-026-001), Chungnam National University Hospital’s IRB (IRB No. CNUH 2018-09-033) and Seoul National University Bundang Hospital’s IRB (IRB No. B-1810/497-001). And this study was registered at Clinical Research Information Service (CRIS, KCT0003411, Date of registration: 03/01/2019).
The screening was conducted based on data of patients who agreed to participate in this study, patients who met the inclusion and exclusion criteria. The target sample size was 144 subjects. Inclusion criteria were 1) those who had a stroke, 2) those who had a score of 10 or more in the Mini-Mental State Examination (MMSE), 3) those who had a Modified Ashworth Scale (MAS) Grade 2 or lower, and 4) those who could stand alone. Exclusion criteria were 1) those with poor cognition that made it difficult to carry out instructions, 2) those with ataxia that made unstable standing balance, 3) those with spasticity MAS Grade 3 or above, 4) those with severe leg arthritis, and 5) those with difficulty walking due to joint problems of the lower leg.
This was a randomized controlled trial and single blind trial. Subjects were assigned into an experimental group or a control group in accordance with a randomized allocation table for subjects who met both the inclusion/exclusion criteria and agreed to participate in this study. Randomization tables were created for each research organization. Randomization was conducted using a random number generator computerized with a block randomization method in SAS version 9.4 (SAS institute Inc., Cary, NC, USA). The single-blind methodology was that the outcome assessors were blind. Intervention and evaluation were performed by different physiotherapists with 5 years or more of experience, in order to increase reliability by minimizing the measurement error. At enrollment, patients were instructed not to reveal their allocation arm to the outcome assessor. The researcher who performed the randomization and data analyses was not involved in any assessment and training.
All patients in both groups were given 30 minutes of training per session, five times per week for four weeks. In addition, both groups performed basic rehabilitation (neurodevelopmental treatment, exercise for range of motion and strengthening). The experimental group received electromechanical-assisted gait training with Exowalk® and the control group received conventional gait rehabilitation treatment by therapists. Because patient’s tolerance and safety of electromechanical gait training compared to physiotherapy need to be considered, Exowalk® facilitates less than 1000 steps in 30 min with a velocity of 1.8 km/h according to initial evaluation, although its maximum velocity is 2.3 km/h. Patients in this study were recommended to receive the electromechanical exoskeleton-assisted gait training at a comfortable speed. For subjects in the control group, the physiotherapist guided and walked the patient while assisting the subject on the side or the back
Analysis of data
In this study, demographic and clinical characteristics of subjects were measured and documented after screening. Demographic information included gender, date of birth, height, weight, and joint problems (or not). Clinical characteristics included the name of the diagnosis, the cause of the disability (brain infarction, cerebral hemorrhage), the paralysis side (Rt., Lt), the possibility of expressing intention (standard: MMSE 10 or higher), and the lower limb spasticity score (standard: MAS grade 2 or lower).
The change in functional ambulatory category (FAC) before and after gait training were primary outcomes to evaluate the efficacy of electromechanical exoskeleton-assisted gait training. FAC was determined the existence of independent walking through a concise level assessment. Primary endpoints were evaluated once at baseline (pre-intervention) four weeks after the baseline (post-intervention), and four weeks after the last treatment (follow-up). FAC was evaluated by dividing the degree of needing for assistance when walking to 1 to 6. FAC level ranged from Level 1 for ‘nonfunctional’ to Level 6 for ‘independent without help for non-level surfaces’.
Secondary outcomes were the changes in Rivermead mobility index (RMI), 10-meter walk test (10mWT), 6-minute walk test (6MWT), Motricity Index (MI), Berg balance scale (BBS) and the changes in spatiotemporal parameters of swing time asymmetry and step length asymmetry. These evaluations were conducted once at baseline (pre- intervention), four weeks after the baseline (post- intervention), and four weeks after the last intervention (follow-up).
Second endpoints had a total of 7 assessments. First, RMI was used to evaluate motor skills. It consisted of 15 questions step by step, depending on the level ranging from bed rotation to running. A total of 15 questions were scored. Each was scored 1 point if yes or 0 if no. The total sum was used as a result of the evaluation. Second, walking velocity as a 10mWT was used to measure the speed during a 10-meter walking. The unit was m/sec (meter per second). Similarly, walking capacity was evaluated with a 6MWT to measure the distance that one could walk for 6 minutes. The unit was m (meter). The fourth item was MI. It was evaluated as 1 to 99 points by measuring the lower leg force level from the ankle to the knee. Assessment items consisted of three questions, each with a score of 0/9/14/19/25/33. The total sum of scores was used as the result of the evaluation. The fifth item was BBS to evaluate the balance ability with 0 to 56 points. There were 14 questions in total. Each question was scored from 0 to 4 points. The total sum of scores was used as the result of the evaluation. The last two evaluation items were measured with motion analysis devices for those who could walk stable without aids. Swing time asymmetry and step length asymmetry were analyzed by HumanTrack (Rbiotech, 1806A_DA004_H1FS, South Korea) a gait analysis system which is capable of performing walking analysis at a distance of 5-7 m without space restriction. The swing time was calculated based on phase of gait begins when the foot first leaves the ground and ends when the same foot touches the ground again. The step length was calculated as the distance between the heel of the foot and the heel of the other foot. Each asymmetry value was calculated as the absolute value difference between the paretic side and the non-paretic side. The physical content of the clinical alteration was reported by auditors, practitioners, and patients at each visit. All indication, data of onset, and period were recorded.
Sample size estimation
Based on results of a previous trial,13 the mean change was 0.54 in the control group and 1 in the test group. Medical devices used in this work were expected to achieve approximately 25% better performance results than the test group, assuming a variation of 1.25. Thus, it was assumed that the difference in the change between the test medical device and the control device was 0.71. The largest value, 1.4, was assumed for conservative access to the standard deviation. Thus, 65 participants were needed for each group to achieve 80% power at a significant level of 0.05. Considering a possible dropout rate of 10%, 144 participants (72 participants per group) were determined to be the sample size.
For demographic and clinical characteristics, categorical variables such as gender, joint problems, disability cause, paralysis side, and lower extremity MAS scores are presented as frequency and percentage. They were analyzed for pre-homogeneity with Chi-squired tests. Continuous variables are presented as mean, standard deviation (SD), and range of minimum and maximum (Min, Max). In case of height and weight satisfying normality, pre-homogeneity was analyzed using student's t-test. For age not satisfying normality, Wilcoxon rank sum test was used.
All values of primary and secondary outcomes are presented as mean and SD (Mean ± SD). Although basic results of FAC were scored 1, 2, 3, 4, 5, and 6 on an ordinal scale, FAC are presented as mean and SD because it was one of the most popular tools for measuring the ambulatory function. Within each group, values of pre and post-intervention changes were analyzed using paired t-test if normality was satisfied or Wilcoxon's signed rank test if normality was not satisfied. In addition, for comparison between pre and post-intervention values of test and control groups, student's t-test and Wilcoxon's rank sum test were performed (Table 2). Stroke duration was the most important factor that affected results. Subgroup analysis compared variations between subjects with stroke durations of 90 days or less (below 90 days) and those with 91 days or more (over 91 days) in the experimental group. For all results, values of pre and post-intervention changes were analyzed using paired t-test if normality was satisfied and Wilcoxon's signed rank test if normality was not satisfied. In order to compare pre-post changes between groups, the analysis was performed using student's t-test and Wilcoxon's rank sum test, depending on whether the normality was satisfied (Table 4). All statistical analyses were performed using SAS version 9.4 or later. All statistical tests were two-sided and the level of significance was set at 0.05.