Pragmatic Home-Based Exercise after Total Hip Arthroplasty - Silkeborg: Protocol for a prospective cohort study (PHETHAS-1)

Objectives

The primary objective is to indicate the preliminary efficacy of home-based rehabilitation using elastic band exercise on performance-based function after THA, based on the relationship between the performed exercise dose and the change in performance-based function (gait speed measured by 40-m fast-paced walk test) from 3 (start of intervention) to 10 weeks (end of intervention) after surgery.

The secondary objective is to investigate if a dose-response relationship exists between the performed exercise dose and changes in: hip-related disability, lower-extremity functional performance, and hip muscle strength.

Study design

The study is a pragmatic, single-center, prospective cohort study (single cohort) conducted in Silkeborg, Denmark. By pragmatic study we mean that the study reflects real life for the involved trial stakeholders. In this study this is for instance reflected by the type and dose of exercise which reflects our current practice. Outcome assessments will be performed at 3 (start of home-based strengthening exercise) and 10 weeks (after 7 weeks of home-based strengthening exercise) after surgery. Furthermore, patient-reported outcome measures will be collected pre-surgery (see the participant timeline in Table 1). It is the aim that all outcome assessments will be performed by three physiotherapists who have been thoroughly trained in performing the outcome assessments. The data collection methods, trial logistics and the intervention have been tested in a pilot study including 10 patients and adjustments have been made accordingly. The study will adhere methodologically to the STROBE guideline for prospective cohort studies and the CONSORT statement.

Study setting

All participants will be included from the Elective Surgery Centre at the public hospital, Silkeborg Regional Hospital. Exercise instruction as well as blinded outcome assessments will be performed by physiotherapists from Elective Surgery Centre. The physiotherapists are members of the staff of physiotherapists at Elective Surgery Centre and all have at least 6 months of experience working with THA.

Participants

Participants will be included by consecutive sampling. The inclusion criteria are: age above 18 years, scheduled for a primary THA at the Elective Surgery Centre due to osteoarthritis and able to understand written and spoken Danish. The exclusion criterion is: referral to supervised rehabilitation in the municipality (instead of the home-based rehabilitation exercise-program in the present study).

Intervention

We define rehabilitation exercise as: “A regimen or plan of physical activities designed and prescribed for specific therapeutic goals. Its purpose is to restore normal musculoskeletal function or to reduce pain caused by diseases or injuries." The exercise intervention in the present study reflects the standard rehabilitation exercise practice at Elective Surgery Centre; hence, a pragmatic approach is used. The exercises in the present trial are comparable to the control intervention in a previous study from our department where we compared usual care (home-based exercise using elastic band resistance) to supervised progressive resistance training in machines and found comparable effects¹⁹. During a short hospital stay (typically discharge on the day after surgery), all patients are instructed in an exercise program of unloaded exercises (not part of the intervention studied) to be performed at home during the initial 3 postoperative weeks until their scheduled follow up visit at the hospital. At this visit (3 weeks after surgery), and after the outcome assessment, the participants will receive a thorough instruction in the strengthening exercises that they are instructed to perform without supervision in their own homes the following 7 weeks. The instruction is conducted one-to-one by physiotherapists using approximately 20 minutes per participant and supported by an instruction booklet with written and illustrated exercise descriptions. The strengthening exercises included are: hip abduction, flexion and extension with elastic band resistance and sit-to-stand. The prescribed training load will be two sets with repetitions to contraction failure (neuromuscular fatigue) and a relative load of 10 to 20 repetition maximum (RM), performed every second day (3–4 times a week). The strengthening exercises are supplemented with daily stretching of hip flexor muscles and balance exercise (one-legged stance). Exercise compliance for the strengthening exercises will be monitored objectively (see Outcomes section). No efforts will be made to increase compliance beyond normal practice (e.g. SMS encouragements, or likewise), because we intent to measure actual, uninfluenced compliance as close to daily practice as possible. The patients are recommended to perform daily walking with increasing distance during their rehabilitation. They are advised to gradually increase their general activity level after the operation to comply with the recommendations on physical activity from the Danish Health and Medicines Authority (≥30 minutes/day of physical activity with moderate intensity + 20 minutes twice a week of physical activity with high intensity). Furthermore, they will be given instructions on how to handle pain during exercises and recreational activities (the pain management guide is available as Extended data)²⁰. To reinforce similar treatment administration, face-to-face meetings among the participating physiotherapists will be held per need to discuss issues experienced in the clinic. The exercise intervention is described in detail according to the exercise-specific Consensus on Exercise Reporting Template (CERT)²¹ (A completed CERT checklist is available as Extended data)²⁰, supplemented with the full set of strength training descriptors as suggested by Toigo and Boutellier (Table 2)²². Finally, the exercise intervention is described according to the Template for Intervention Description and Replication (TIDieR) checklist, which is a generic intervention-description template (a completed TIDieR checklist is available as Extended data)^20,23.

Patient information

The participants will be advised to gradually increase their activity level after the operation. Likewise, they will be instructed to gradually progress their exercises during the 7 weeks of training at home according to the described progression model, where the strengthening exercises are performed to failure in each set; when the possible repetitions exceed 20 in two of the three elastic band exercises they should change the elastic band so that a higher loading is possible. The participants are instructed that pain in relation to exercise is normal, and that up to 5 on a numeric rating scale (NRS) during exercise is considered acceptable based on the suggested pain monitoring system by Thomée et al.²⁴. However, the pain should decrease within 30 minutes after the exercise session. The participants are advised to contact the hospital if they experience increasing pain or other complications such as swelling or wound problems (the pain management guide is available as Extended data)²⁰.

Outcomes

Exposure. Performed exercise dose will be quantified as the total physiological exercise stimulus (Time under tension summary dose per week) recorded by a sensor (Bandcizer: commercially available from www.bandcizer.com) attached to the elastic exercise band. The sensor automatically switches on and stores data when the elastic exercise band is used^13,14. Furthermore, performed exercise dose will be quantified as the number of days with strengthening exercises being performed.

Primary outcome

Change in gait speed is chosen to be primary outcome, as walking ability is considered the most important function to improve by patients undergoing THA surgery²⁵. Furthermore, the 40-m fast-paced walk test is part of the core set of functional tests to include in clinical trials in patients with osteoarthritis in hip or knee recommended by OARSI^26,27.

Secondary outcomes

Other pre-specified outcomes

Changes to outcomes after trial registration

Embedded qualitative study (PHETHAS-2)

In addition to collecting quantitative data, we will also conduct an embedded qualitative study concerning the participants' experience with performing home-based exercise and resuming general physical activities. The aim will be to understand the patients' motivation and barriers related to home-based exercise and general physical activity after THA. The participants will be selected through theoretical sampling³³, expectedly a maximum of 20. Participants will be recruited partly from the PHETHAS-1 trial, and partly from the population of standard THA patients not involved in an exercise trial. This is done to elucidate the influence of participating in a trial with extra interventions such as exercise diary, outcome assessments, etc. Semi-structured interviews will be conducted 10 weeks postoperatively using an interview guide (available as Extended data)²⁰. This qualitative study is undertaken to refine the home-based intervention for future trials and clinical implementation. The embedded qualitative study will be reported in a separate paper with a clear reference to the PHETHAS-1 trial.

Sample size

The sample size estimation is based on a minimal clinical important difference of 0.2 m/sec³⁴ between changes in gait speed among participants with highest performed exercise dose compared to participants with smallest performed exercise dose. Based on results from a pilot study leading up to this trial, we expect a maximal difference of 4 hours in performed exercise dose (total Time under tension summary dose) during the 7-week intervention period between participants with highest and lowest exercise compliance. Also based on the pilot study, a SD of 1.06 hours for exercise dose and 0.16 m/sec for change in gait speed were used. The power is set at 0.90 to increase the power for secondary analyses, and with a 0.05 level of significance. Based on the above, the required sample size is estimated to be 88 participants.

Recruitment

The basis for recruitment makes the trial highly feasible due to the approximately 800 elective THA procedures performed annually at the Elective Surgery Centre. As there may be more eligible participants per day than for whom there is available equipment (BandCizers and ActivPAL sensors), we restrict inclusion by including consecutive participants from random sections of the department. That is, patients examined and booked for surgery in pre-specified clinics in the outpatient department. Patients are allocated to the specific clinics in the department by a secretary at random and with no influence from any personnel involved in the study. The estimated inclusion rate is approximately one to two participants per week; please see estimated participant flow and current recruitment status in Figure 1.

Figure 1. Estimated participant flow.

Blinding

The outcome assessors will be blinded to exercise compliance-data. Moreover, we will inform the participants that we measure how they perform their exercises and not how much they exercise or what the study hypothesis is. This is done with the purpose of minimizing sensor-induced influence on compliance and to reduce expectation bias.

Data collection methods

The elastic band sensor (BandCizer) automatically records and stores exercise data during elastic band exercises. It is a valid measure of date, time of day, number of repetitions and sets, total time-under-tension (TUT), and total single repetition TUT during commonly used home-based strength training exercises for the lower extremities¹⁴. The 40-m fast-paced walk test measures performance-based function and is part of the recommended core set of tests to assess physical function in people diagnosed with hip or knee osteoarthritis by the Osteoarthritis Research Society International (OARSI)^26,27. A high inter-tester reliability is shown (intraclass correlation coefficient (ICC) 0.95) in a population with hip osteoarthritis³⁴. The HOOS questionnaire measures patient-reported outcome in the subscales: symptoms, pain, ADL, function in sport and recreation and hip-related quality of life²⁸. HOOS is shown valid, responsible, and reliable (ICC >0.78) when evaluating patients undergoing THA³⁵. Hip muscle strength²⁹ and 30-s chair stand test will be conducted in accordance with previous published methods^27,29 showing acceptable relative and absolute inter-rater reliability when used after THA (ICC 0.83-0.93 and SEM 7–10%)³⁶. General Self-Efficacy Scale is a 10-item validated questionnaire holding a scale assessing optimistic self-beliefs to cope with a variety of difficult demands in life, scored between 1–4 points without any defined cut-off point³⁰. ActivPal movement-sensors measures physical activity as time spent in the sit/lie position (X-axis), standing (Y-axis) and walking (Z-axis). It has been validated in several studies in healthy adults³⁷ and in older adults with a hip fracture^38,39.

Data collection will continue for participants who discontinue their training. Data collection will only be discontinued if participants explicitly withdraw from the study or any major events or diseases prevent the outcome assessments. If participants do not attend their scheduled follow ups, they will be contacted and offered a new time.

Data management

Raw data from the Bandcizer will be uploaded to a secure online database using a tablet or smartphone. Here, the investigator will be able to access and analyze data and extract the following variables; date and number of training sessions, number of repetitions, time under tension for each repetition and total time under tension for each training session. Data from the outcome measurement will be double entered in EpiData 3.1 using anonymous coding with ID numbers and relevant range checks for data values to minimize typing errors. Completed data collection forms will be stored in a locked cabinet at Silkeborg Regional Hospital. Electronic data files will be stored on a secured hospital server with access requiring personal login. The linkage between ID numbers and personal identification data (e.g. civil registration number, name, address) will be stored as an electronic file as described above.

Statistical methods

All the planned analyses are listed in Table 3.

Descriptive analyses will be performed for demographic variables, supplementary descriptive variables, adverse events, motivation to perform prescribed exercises, evaluation of prescribed exercises and pain after exercise sessions (change in pain and pain flares). Data will be presented as means with 95% confidence intervals (CI) or medians with inter quartile ranges (IQR) for continues variables and as frequencies with percentages for categorical variables.

Primary analysis

Initially, scatterplots of outcome variables and exercise dose variables will be used to suggest starting model structures and possible more complex alternatives. The structures of the models used for the dose-response analysis will depend on the specific relationship between change in gait speed and the exercise dose variable. Because of this, and not having any prior knowledge of the structure of the relationship, multiple models will be fitted and evaluated by R-squared values to identify the models that fit data the best. As a starting point, the first model will be fitted as a fixed increase in outcome, based on exercise dose-change done by linear regression modelling. If necessary, more complex regression such as polynomial relationship and other nonlinear structures will also be evaluated.

In the case that none of the models seem to fit the data, a linear regression model with a categorical variable based on intervals of the exercise dose variable will be fitted. This model does not provide a direct dose response relationship but provides an estimate of the association between the outcome variable and the exercise dose variable within the specific intervals.

“Regression to the mean” may be present and will be evaluated by the correlation between the change and the measure at baseline. If regression to the mean is believed to be present for an outcome, the models of the outcome will additional include the baseline measure to adjust for regression to the mean.

Possible confounding variables (self-efficacy (baseline), physical activity (during intervention), and gait speed (baseline)) will also be included in the models. The confounding effect of each variable will be examined by comparison of dose response estimates in models with and without the confounder. If there is no relevant change between the estimates of the models, the confounder will be excluded from the model. Normality assumptions in the models are evaluated by QQ-plots

Secondary analyses

For the dose response relationship between change in HOOS ADL, the analysis will be similar to the analysis for change in gait speed outlined above.

The relationship between exercise compliance and HOOS subscales (symptoms, pain, quality of life), 30-s chair stand test and hip muscle strength will be presented as means with CIs or medians with IQRs within each of the compliance quartiles, as well as graphical representation of these values.

Exploratory analyses

To better understand what may relate to how patients comply with prescribed rehabilitation exercise after THA, we will investigate how different variables relate to exercise compliance (dependent variables: time under tension summary dose and total number of exercise sessions), using uni-variable modelling. Independent variables will be: pain flares (first two weeks of intervention), pain flares (entire intervention period), HOOS pain (baseline), motivation to perform exercises, belief in effect of exercises, self-belief in compliance to exercising, satisfaction with rehabilitation exercise, physical activity (mean upright time/day and mean number of steps/day) and self-efficacy (baseline).

To better understand what may relate to how physically active patients are after a THA, we will investigate how different variables relate to physical activity (dependent variables: mean upright time/day and mean number of steps/day), using univariate modelling. Independent variables will be: pain flares (first two weeks of intervention), HOOS pain (baseline), motivation to perform exercises, self-belief in compliance to exercising, and self-efficacy (baseline).

In the analysis of "result of the operation", the change in score from baseline to follow-up will be presented for each HOOS subscale (pain, symptoms, ADL, QOL) and gait speed. Data will be presented both for each response category of the anchor question, and for the subgroup of patients, who answered "excellent", "very good" or "good" data. This subgroup is considered to be reporting a hip-specific acceptable symptom state. Data will be presented by means with 95% CI or medians and interquartile ranges (IQR). In each response category of the question for "change in hip problems", the change in score from baseline to follow-up will be presented for each HOOS subscale (pain, symptoms, ADL, QOL) and gait speed. Data will be presented by mean scores with 95% CI or median and inter quartile range (IQR).

Furthermore, for each exercise dose quartile, the percentage of patients in each response category of the questions for "result of the operation" and "change in hip problems", will be presented graphically. Finally, HOOS cut points for PASS and MCII will be estimated by the mean score or mean change approach⁴⁰.

Handling of missing data

Based on the importance of the Bandcizer data, we have planned for how to use the data if we are not able to extract it as planned. Thus, we prioritize to use the Bandcizer data the following way depending on what is possible:

1) As planned with a valid total time-under-tension (TUT) estimate.

2) If 1) is not possible, we will use the total number of repetitions as an estimate of the total exercise dose.

3) If 1) and 2) is not possible, we will use the total number of days with performed exercise as an estimate of the total exercise dose.

We will report the proportion of missing data, e.g. self-reported non-compliance in Bandcizer use or invalid Bandcizer sensor-data. Furthermore, we will perform a sensitivity analysis using data on total exercise dose (days with exercise) from the exercise diary. This will inform if there is a comparable dose-response relationship when analyzing self-reported compliance data compared to objectively measured data (Bandcizer). The two types of data yield a risk of different types of bias. Self-reported exercise dose is often over-estimated and the Bandcizer data may induce problems with missing data as described above which could led to an underestimation of exercise-dose.

Missing items within the HOOS and General Self-efficacy scale will be handled as recommended in the guidelines (HOOS: <50% missing items in each subscale is accepted, self-efficacy: ≤3 missing items is accepted). Concerning ActivPal data, a minimum of four days of data collection will be accepted as sufficient to calculate min/day upright time and steps/day⁴¹. In situations where participants have to stop the physical tests due to pain, the data from the best performance are used no matter if the pre-defined number of repetitions is reached. It is noted if tests are interrupted due to pain to be able to perform sensitivity analysis if appropriate. If participants are lost to follow up (despite the before-mentioned efforts to keep every participant in the trial) they will be excluded from the analyses that include change scores. We will not use last-observation-carried-forward or other imputation procedures on exposure (exercise dose), as we aim to investigate relationships between actually performed exercise dose and changes in post-operative outcomes. However, on possible confounding variables that are included in the model, we will use multiple imputation if needed to retain the sample size of n=88 in the analysis. Models used in the imputation will include the remaining confounders with measures as predictors.

Data monitoring

Since the study involves no major changes to current practice it is not deemed necessary to establish a data monitoring committee or perform any interim analyses. Likewise, no provisions for post-trail care will be made.

Strength and limitations

The strengths of this study include the objectively measured exercise dose, the standardized and thoroughly described intervention and the inclusion of outcome variables at all levels in the International Classification of Function, Disability and Health (ICF). We chose gait speed measured by the 40-m fast-paced walk test as the primary outcome. Walking ability is considered the most important function to improve by patients undergoing THA surgery²⁵, and the 40-m fast-paced walk test is part of the core set of functional tests to include in clinical trials in patients with osteoarthritis in hip or knee recommended by OARSI²⁶. An important candidate for the choice of primary outcome for clinical research has been suggested to be a patient-reported one⁴⁴. Nevertheless, we chose a performance-based measure as the primary, as we were concerned about ceiling effects on patient reported outcomes that measures function and pain, such as the HOOS questionnaire after THA⁴⁵.

Multiple factors can potentially affect exercise compliance; therefore, we include measurements of physical activity and self-efficacy. Also, it is not known which outcomes that is most susceptible to exercise dose which is why we include a broad range of different outcome types to be able to explore potential dose-response relationships.

Blinding of participants in randomized exercise trials are often impossible, in the present study we seek to blind the participants to the specific focus om exercise dose, they are just told that we measure "the way they exercise". Hypothesis blinding is considered a design strength when blinding of participants regarding treatment is not possible⁴⁶. Furthermore, we blind the outcome assessor in the sense that they are not allowed to see the exercise diary or BandCizer data prior to the outcome assessment.

Research ethics approval

The Ethics Committee of Central Denmark Region accepted initiation of the study and reviewed the study as non-notifiable (Inquiry 270/2017). The study was approved by the Danish Data Protection Agency (ref. no: 1-16-02-589-15).

Informed consent

Trained Research staff (nurse or physiotherapist) will provide presentation of comprehensible information about the research to potential participants, confirmation that they understand the research, and assurance that their agreement to participate is voluntary. Potential participants will also receive information sheets. They will be offered deliberation time and, subsequently, written consent will be obtained from those who choose to participate. The informed consent document is available as Extended data²⁰.

Confidentiality

All records that contain names or other personal identifiers, such as informed consent forms, will be stored separately from study records identified by code number to protect confidentiality before, during, and after the trial.

Future availability of trial data

The principal investigator, as well as all co-authors, will have access to the full dataset as needed. A fully anonymized dataset and statistical analysis code will be made available for the scientific journal reviewing the manuscript within six months in line with the recent proposal from the International Committee of Medical Journal Editors (ICMJE)⁴⁷.

Dissemination policy

Results from the trial will be published in international, scientific peer-reviewed journals, no matter the trial outcome. The results will also be presented at relevant scientific conferences and symposiums. Authorships will be allocated according to the ICMJE recommendations. The following papers are planned:

Underlying data

No underlying data are associated with this article.

Extended data

Figshare: PHETHAS-1 protocol. https://doi.org/10.6084/m9.figshare.8256014²⁰.

This project contains the following extended data:

Extended data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).

Reporting guidelines

Figshare: SPIRIT checklist for “Pragmatic Home-Based Exercise after Total Hip Arthroplasty - Silkeborg: Protocol for a prospective cohort study (PHETHAS-1)”. https://doi.org/10.6084/m9.figshare.8256014²⁰.