Study design and randomization
The study is a prospective, randomized, controlled, parallel-group, open-label with blinded assessor trial that is conducted according to the SPIRIT recommendations [12]. Following informed consent, patients are randomized (with a 1:1 allocation ratio) to a control group or an experimental group (Figure 1). Computer-generated randomization lists are used (using the website www.random.org) to sequentially distribute the patients into one of the two groups. Generation of the allocation sequence and assignment of participants to interventions are performed by one of the authors (MDM).
The study conforms to the guidelines of the Declaration of Helsinki, was approved by the local ethics committee (“Comitato Etico Interaziendale AOU Città della Salute e della Scienza di Torino”: protocol n. 0107065), and registered at the ClinicalTrial.gov website (identifier NCT04176315).
Study setting and patients
The study setting is a rehabilitation clinic where patients of both genders who had undergone primary THA surgery are recruited. Inclusion criteria are: i) ability to understand and accept the study procedures and to sign an informed consent form, ii) good familiarity with the Italian language, iii) good predisposition to the use of technology or availability of a caregiver providing technological support to the patient, iv) availability to move to the rehabilitation clinic for a final visit. Exclusion criteria are: i) age <60 or >80 years and body mass index > 35 kg/m2, ii) admission after THA revision surgery, iii) contralateral hip osteoarthritis severely limiting patient mobility and ability to comply with a rehabilitation program, iv) aphasia, dementia, or psychiatric comorbidity interfering with communication or adherence to the rehabilitation process, v) respiratory, cardiac, metabolic, or other condition limiting patient mobility and ability to comply with a rehabilitation program, vi) major medical complications occurring after surgery that prevented the discharge of the patient within 10 days after the surgery.
Interventions
Patients in both groups receive a standard rehabilitation protocol during the 2-week stay in the rehabilitation clinic, as directed by the medical staff, aimed to improve the hip range of motion (ROM), the global neuromuscular performance (walking, chair rise, etc.), and the strength of hip and lower leg muscles. The program consists of 3 hours / day of physiotherapy during week days (between Monday and Friday), and 1 hour of activity on Saturday for a total of 16 hours of activity per week.
In addition, patients in the experimental group perform also 1-2 sessions per week (2-4 sessions in total) of supervised familiarization with the ReHub telerehabilitation system (see below). Patients in the control group perform 1-2 sessions per week (2-4 sessions in total) of supervised familiarization with a printed guide describing the exercises to be performed at home (Figure 1).
After discharge from the rehabilitation clinic, patients in the control group follow the standard home-based care (they receive a guide to performing the exercises and they are asked to fill out a diary questionnaire designed to assess the adherence to the rehabilitation program), while patients in the experimental group follow a home-based telerehabilitation and telemonitoring program by using ReHub.
The home-based rehabilitation program consists in the execution (unsupervised for the control patients, ReHub-assisted for the experimental patients) of the following 5 exercises: 1) hip flexors: with a lateral support, flexion of the hip joint up to a maximum of 90° of ROM while bending the knee; 2) quadriceps (eccentric contraction): with a front support, lunge with both legs while bending the knees; 3) hip abductors: with a front support, abduction of the hip joint (with both knees extended) until the maximum ROM is allowed; 4) hip extensors: with a front support, extension of the hip joint until the maximum ROM is allowed; 5) sit-to-stand: standing up from a chair and sitting down on it sequentially, with one foot slightly in front of the other and without the support of the upper limbs (arms are crossed at the wrists and held against the chest).
Patients are asked to perform the rehabilitation protocol according to the following workload: i) daily execution of a single exercise session for three weeks, ii) three series of ten repetitions for each exercise, iii) bilateral execution of exercises 1-3-4.
Concomitant care permitted during the home-based rehabilitation program includes the use of analgesics, when needed.
Criteria for discontinuing interventions include participant request and intolerance to the rehabilitation program.
Retention of study participants is performed according to the following strategies: use of a systematic method for patient contact and appointment scheduling, study reminders, emphasizing study benefits.
Provisions for post-trial care will consist in the standard care within the National Health Service.
Adverse events reporting and harms
Any unfavourable and unintended sign, symptom or illness that develops or worsens during the period of the study is classified as an adverse event, whether or not it is considered to be related to the study treatment. Adverse events may include: an exacerbation of a pre-existing illness; a condition that is detected after trial intervention administration; and continuous persistent disease or a symptom present at baseline that worsens following administration of the trial treatment – and may be expected or unexpected. The number (events and individuals) and nature of all adverse events reported to blind and unblind members of the research team are recorded. The period for adverse event reporting is following the signing of the study consent form until last follow-up assessment. All adverse events are recorded and reviewed by the chief investigator (MAM).
Blinding and outcomes
A blinded physician (GC) completes all functional assessments and gathers all clinical data on the electronic medical record of each patient, as reported in Figure 2.
The following clinical data are acquired from electronic patient files and clinical assessments: gender, age, body mass index, length of hospital stay.
The primary outcome is physical performance assessed through the Timed Up-and-Go (TUG) test that measures the time required for standing up from a chair, walking straight for 3 m, turning, walking back to the chair, and sitting down [13].
Secondary outcomes include: i) independence level (assessed through the Functional Independence Measure – FIM – scale) [14], ii) resting and movement pain intensity (assessed through a Numerical Rating Scale with 0 corresponding to “no pain” and 100 corresponding to the “worst imaginable pain”): resting pain intensity is measured prior to any study procedures, while movement pain is measured during active hip flexion and extension, iii) hip disability (assessed through the Hip dysfunction and Osteoarthritis Outcome Scale – HOOS) [15], iv) hip ROM and muscle strength (see below); v) patient’s perception of clinical improvement (assessed through a 6-point Likert scale investigating the global rating of change - GROC: 1 = much worse; 2 = worse, 3 = same, 4 = improved, 5 = much improved, 6 = completely recovered).
All outcomes are assessed at three points [see Figures 1 and 2 - baseline visit (t1): rehabilitation clinic admission; follow-up visit (t2): rehabilitation clinic discharge; final visit (t3): 3 weeks after discharge], with the exception of the GROC score that is assessed at the final visit only.
Assessment of hip ROM and muscle strength
All ROM tests are conducted (using a manual, plastic, 2-arm goniometer with 1 degree increments) by a single physiotherapist, blinded as to the allocation group. Only the passive ROM of the operated side is assessed in the following order: flexion, extension, abduction. Hip flexion and abduction ROM are measured with participants in the supine position, while hip extension ROM is measured in the sidelying position.
The maximal isometric voluntary contraction of the operated side is assessed using a wall-fixed dynamometer (model HCB 99K50, Kern & Sohn, Balingen - Germany). Muscle strength tests are performed in the following order: knee extension, hip extension, hip abduction. Knee extension is assessed with participants in the sitting position, with both hip and knee at 90° flexion. Hip extension and hip abduction are measured with participants in the standing position, with the body weight supported by the contralateral lower limb, hip in the neutral position and knee in the extended position.
ReHub telerehabilitation system
ReHub is a digital platform for physical rehabilitation that offers personalized design and monitoring of therapeutic exercise programs to recover the functional capacity of the musculoskeletal system. The solution is composed of two main pillars: a cloud platform and a sensorized exercise kit. The cloud platform establishes effective communication between the patient and the healthcare professionals in charge of their rehabilitation. It allows physical therapists to create a rehabilitation program specifically tailored to each patient’s condition. Patients use the cloud platform to perform the exercises in their rehabilitation program with the help of DyCare’s proprietary wearable sensor that captures 3D motion data. The sensor is integrated into different exercise tools, although only a body strap is used in this study as the selected exercises do not require additional tools. The sensor records biomechanical parameters (such as ROM and movement speed) in real-time when used on the indicated body part while exercising. When patients do their prescribed exercises at home, intelligent algorithms deliver real-time biofeedback through a User Interface and a Virtual Coach. The results can be viewed by the physical therapist to follow the progress of the patient, adapt the program remotely if needed or chat with the patient by online messaging module through the platform.
Sample size estimation and statistical analyses
To elucidate a difference in physical performance between the intervention and the control group, we used data from previous studies (average ± standard deviation of the TUG score in patients discharged home after post-surgery rehabilitation of 13 ± 3.5 s and TUG minimal detectable change of 2.5 s) [16, 17] to determine the required sample size. Twenty-five participants per group will provide adequate power to detect a statistically significant differences in TUG score between the two groups (allocation ratio 1; statistical power: 80%; alpha level: 0.05), but 56 patients will be recruited in total anticipating a drop-out rate of 10%.
The statistical analysis over the results will be performed by a blinded expert. The Kolmogorov–Smirnov test will be adopted to check the normality of data distribution. Within and between-group comparisons will be performed by two-sample t-test or one-way and two-way ANOVA.
The extent of missing data will be explored in the outcomes, especially the primary outcome. Patterns of missing data will be explored and predictors of missingness examined, especially if these vary by intervention. If necessary, multiple imputation will be used to impute missing data assuming the missingness mechanism is missing at random. A detailed statistical analysis plan will be agreed to before the end of data entry and before the treatment code is broken.
Data will be expressed as mean standard deviation (normally distributed data) or median and interquartile range (non-normally distributed data). The threshold for statistical significance will be set to P = 0.05. All statistical tests will be performed with Matlab (The MathWorks, Inc., Natick, Massachusetts, United States) software package.