Description

DESIGN

The EduEx trial will be a multicentre, stratified (by site), block randomized (allocation 1:1), controlled, parallel-group superiority trial. 150 people with hip OA will be recruited from the Orthopedic Departments at hospitals and from physiotherapy clinics, social media and newspapers. Participants will be randomized to PRT+EDU or EDU.

All 150 participants will be included in the clinical evaluation study (CLIN) while only the last 40 participants randomized to PRT+EDU and EDU, respectively, will also be included in the mechanistic evaluation study (MECH, n=80), by being asked to participate in additional outcome assessments including magnetic resonance imaging of the hip.

The primary endpoint will be the 12 months follow-up for both the CLIN and MECH study, while the secondary endpoint will be the 3-month follow-up.

RANDOMIZATION

After baseline assessment, participants will be randomized in a 1:1 ratio to PRT+EDU or EDU. A computer-generated list of random numbers will be generated in the Research Electronic Data Capture (REDCap) system. The randomization will be stratified by site and block randomized, to ensure equal distribution of allocations among trial sites. Two lists of random numbers will be generated, one for the first 70 participants and one for the last 80 participants recruited, to enable an even distribution of treatment allocation of the 80 participants in the MECH subsample. Treatment allocation will be concealed as one of the principal investigators will use the randomization tool only after the baseline assessment has been performed.

INTERVENTIONS

The PRT and EDU interventions will be conducted either at the collaborating hospital departments or physiotherapy clinics across Denmark.

PRT: Participants allocated to receive PRT will attend 3 months of supervised PRT followed by 9 months of unsupervised PRT with the addition of 8 exercise booster sessions. The PRT program consists of two weekly training sessions (60 min per session) with ≥48 hours of rest between sessions. All supervised PRT sessions will be group-based (up to 5 participants) supervised by one physiotherapist.

EDU: Both treatment arms will attend three EDU sessions provided by a trained physiotherapist involving important disease-specific information. The sessions will address knowledge of OA, treatment options with a specific focus on physical activity recommendations, advice on self-management and more. All three sessions will emphasize on engaging the participants actively and sharing experiences with each other.

STATISTICAL ANALYSIS PLAN

The analyses will be based on the between-group difference in change in the primary and secondary outcomes from baseline to the 12 months follow-up, according to the intention-to-treat (ITT) principle. Additionally, per protocol analyses will be performed including only participants with high adherence to the EDU sessions (at least 2 sessions attended) and high adherence to the exercise sessions (≥80% of the planned sessions completed) and high exercise fidelity (≥80% of prescribed repetitions performed). Between-group comparisons of change from baseline to follow-up in the primary and secondary continuous outcomes will be analysed using a repeated measures mixed model with participants and sites as random effects and with visits and treatment arm as fixed effects.

DATA MANAGEMENT

All data and outcomes collected from participants will be entered into the REDCap database. For the patient reported outcomes, participants will fill out questionnaires directly into REDCap. If a participant is unable to do so, they will fill out paper versions of the questionnaires and the tester will enter it into REDCap and shred the paper versions. The data will be maintained in storage for five years after trial termination.

PATIENT AND PUBLIC INVOLVEMENT

In the EduEx trial we have established an advisory board of four patients with hip osteoarthritis and a physiotherapists. Patients and physiotherapists have been invited to participate in the board throughout the research project. The board have and will continue to influence clinical outcomes, practicalities, and content of the interventions. The board will have one meeting every three months during the planning, conducting and dissemination processes of the trial and will give advice (consultation level of involvement) throughout.

ETHICAL CONSIDERATIONS

The study intervention is non-invasive and is expected to result in a generally optimized health status of the included participants. Approval from the Central Denmark Region Committee on Health Research has been obtained for the EduEx trial. Written informed consent will be obtained from all participants prior to inclusion and the project will be performed in accordance with the Helsinki Declaration. Authorship eligibility will be based on the recommendations from The International Committee of Medical Journal Editors. Any important protocol amendments for The EduEx trial will be registered at ClinicalTrial.gov and reported to the Central Denmark Region Committee on Health Research.

RESEARCH RESULTS

The results from this trial will be published in peer-reviewed scientific journals and presented at congresses, regardless of whether the results are inconclusive, negative or positive.

There are 3 preplanned studies to be conducted on the results from this trial that will be reported in 3 separate research papers:

1. The primary clinical evaluation study (CLIN) comparing effects of PRT+EDU and EDU alone on the primary outcome of HOOS ADL is study number one.
2. The primary mechanistic evaluation study (MECH) comparing PRT+EDU and EDU alone on changes in hip joint tissue is study number two.
3. A secondary MECH evaluation study (MECH2) is study number three, in which the mechanisms of exercise are investigated by looking at associations of changes in other outcomes with the changes seen for hip pain and physical function.