ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12620001041943

Ethics application status

Approved

Date submitted

14/09/2020

Date registered

13/10/2020

Date last updated

21/01/2022

Date data sharing statement initially provided

13/10/2020

Type of registration

Prospectively registered

Titles & IDs

Public title

Education and activity programs to improve health in people with painful knee osteoarthritis. A randomised controlled trial with cost-effectiveness analysis

Scientific title

Education and activity programs to improve health in people with painful knee osteoarthritis. A randomised controlled trial with cost-effectiveness analysis

Secondary ID [1]

National Health and Medical Research Council (NHMRC) of Australia project grant ID 1161634

Universal Trial Number (UTN)

U1111-1249-1672

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Knee osteoarthritis

Condition category

Condition code

Musculoskeletal

Osteoarthritis

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Description of interventions/exposure:
The two groups will have consistent graded walking and strengthening components, but a contrasting education component.

Intervention A:
Participants will attend four, 60-90 minute, in-person sessions with a physiotherapist at weekly intervals (over 4 weeks), during which they will receive Education A, a graded walking program and strengthening exercises. All in-person sessions will take place at the private physiotherapy clinic where the trial physiotherapist is employed. The in-person sessions will be followed by 4 weeks of at home activities (workbook and walking/strengthening progression) with weekly telephone calls or telehealth sessions by the Physiotherapist (20 mins each). A follow-up telephone call/telehealth sessions at 3 months (20 mins) and follow-up in-person sessions with the Physiotherapist (45-60mins) at 5 and 9 months will occur. All treatment components, including choice of telephone/telehealth for home sessions, will be individualised to the participant. To protect trial blinding, the nature of the treatment is being withheld from the registry but has been provided privately to ANZCTR staff and will be made publically available at the conclusion of the trial. The trial intervention will be provided by physiotherapists with a minimum of 5 years clinical experience.

Intervention adherence: This will be assessed via review of attendance records for in-person physiotherapy appointments, via review of participant workbook, walking, and strengthening diaries, and through adherence rating scales completed by participants.

Intervention fidelity: A random sample of treatment sessions (minimum of one for each therapist) will be audio recorded to allow audit of intervention fidelity for each group. Each physiotherapist (and physiotherapist clinic) will only provide one of the study interventions. Therapists’ case notes for each session, recorded via standardised templates, will also be used to evaluate intervention fidelity (e.g., ensure other treatments not given).

Intervention code [1]

Treatment: Other

Intervention code [2]

Lifestyle

Intervention code [3]

Behaviour

Comparator / control treatment

Intervention B:
Participants will attend four, 45-60 minute, in-person sessions with a qualified physiotherapist at weekly intervals (over 4 weeks), during which they will receive Education B, a graded walking program and strengthening exercises. All in-person sessions will take place at the private physiotherapy clinic where the trial physiotherapists is employed. The in-person sessions will be followed by 4 weeks of at home activities (workbook and walking progression) with weekly telephone calls/telehealth sessions by the Physiotherapist (20 mins each). A follow-up telephone call/telehealth session (3 months) and follow-up in-person sessions with the Physiotherapist (30-45mins) at 5 and 9 months will occur. The walking and strengthening program will be personalised to the participant. To protect trial blinding, the nature of the treatment is being withheld from the registry but has been provided privately to ANZCTR staff and will be made publically available at the conclusion of the trial. The trial intervention will be provided by physiotherapists with a minimum of 5 years clinical experience.

The same protocols for assessing intervention adherence and fidelity as Intervention A group will be followed.

Control group

Active

Outcomes

Primary outcome [1]

Western Ontario McMaster Universities OA Index (WOMAC) Total score

Timepoint [1]

Baseline, week 12, week 26, and week 52 (primary timepoint)

Primary outcome [2]

Physical activity level: Wrist-based accelerometry (GT9X Actigraph, Pensacola, US) will assess average daily step count over 7 days.

Timepoint [2]

Baseline, week 12, week 26, and week 52 (primary timepoint)

Secondary outcome [1]

Average pain over the past week will be assessed using an 11-point Numeric Rating Scale (NRS), and where 0 = no pain and 10 = worst pain possible.

Timepoint [1]

Baseline, week 12, week 26, week 52

Secondary outcome [2]

Knee pain intensity during walking: Average pain during walking over the past week will be assessed using a 11-point Numeric Rating Scale, where 0 = no pain and 10 = worst pain possible.

Timepoint [2]

Baseline, week 12, week 26, week 52

Secondary outcome [3]

Physical activity level: Wrist-based accelerometry (GT9X Actigraph, Pensacola, US) will assess average daily minutes of light, moderate, and vigorous physical activity

Timepoint [3]

Baseline, week 12, week 26, week 52

Secondary outcome [4]

Western Ontario McMaster Universities OA Index (WOMAC) Pain Subscale

Timepoint [4]

Baseline, week 12, week 26, week 52

Secondary outcome [5]

Western Ontario McMaster Universities OA Index (WOMAC) Function Subscale

Timepoint [5]

Baseline, week 12, week 26, week 52

Secondary outcome [6]

Pain self-efficacy as assessed by the Pain Self-Efficacy Questionnaire

Timepoint [6]

Baseline, week 12, week 26, week 52

Secondary outcome [7]

Depression as assessed by the 4-itme PROMIS Depression subscale

Timepoint [7]

Baseline, week 12, week 26, week 52

Secondary outcome [8]

Anxiety as assessed by the 4-item PROMIS Anxiety subscale

Timepoint [8]

Baseline, week 12, week 26, week 52

Secondary outcome [9]

Stress as assessed by the 4-item Perceived Stress Scale

Timepoint [9]

Baseline, week 12, week 26, week 52

Secondary outcome [10]

Fear of movement as assessed by the Brief Fear of Movement Scale

Timepoint [10]

Baseline, week 12, week 26, week 52

Secondary outcome [11]

Pain catastrophising as assessed by the 4-item Pain Catastrophizing Scale (PCS)

Timepoint [11]

Baseline, week 12, week 26, week 52

Secondary outcome [12]

Health-related quality of life as assessed by the EQ-5D-5L (used for health economic analyses)

Timepoint [12]

Baseline, week 12, week 26, week 52

Secondary outcome [13]

Perception of the knee as assessed by the Fremantle Knee Awareness questionnaire

Timepoint [13]

Baseline, week 12, week 26, week 52

Secondary outcome [14]

Global rating of change (GROC) as assessed by a 7-point Likert scale (1 = Much worse; 3 = No change; 7 – much better)

Timepoint [14]

Week 12, week 26, week 52

Secondary outcome [15]

Mediating factor: Conceptualisation of OA as assessed by the Osteoarthritis Pain and Physical Activity Conceptualisation Scale (custom-designed; psychometrics currently being evaluated)

Timepoint [15]

Baseline, week 12, week 26, week 52

Secondary outcome [16]

Mediating factor: Self-regulated learning ability (items taken from the Motivated Strategies for Learning Questionnaire and Regulation of Learning Questionnaire)

Timepoint [16]

Baseline, week 12, week 26, week 52

Secondary outcome [17]

Exploratory factor: Implicit movement bias as assessed by a computer-based implicit association test. [Note: this test might only be administered in a sub-sample of participants].

Timepoint [17]

Baseline, week 12

Secondary outcome [18]

Exploratory factor: Implicit environmental bias as assessed by hill steepness estimations using a computer-based task and via head-mounted display. [Note: this test might only be administered in a sub-sample of participants].

Timepoint [18]

Baseline, week 12

Secondary outcome [19]

Exploratory factor: Walking distance estimation task as assessed by in-person estimation of distance to set locations and estimation of ability to walk to those locations.

Timepoint [19]

Baseline, week 12

Secondary outcome [20]

Implicit motor imagery as assessed by left/right judgment tasks (for hands and feet images) using an app on a smartphone or tablet.

Timepoint [20]

Baseline, week 12

Secondary outcome [21]

Two point discrimination threshold as assessed using digital callipers; measured at the medial aspect of the knee (trial knee and control knee).

Timepoint [21]

Baseline, week 12

Secondary outcome [22]

Sensitivity to physical activity as assessed by the change in pain intensity from the start to the end of a modified 6-minute walk test (pain intensity measured at each minute)

Timepoint [22]

Baseline, week 12

Secondary outcome [23]

Osteoarthritis knee drawing: to assess changes in understanding of pain and the process of knee osteoarthritis, participants will be asked to ‘draw your osteoarthritis and how it hurts’. This will be a hypothesis generating measure.

Timepoint [23]

Baseline, week 12, week 36 (at 9-month in-person session)

Secondary outcome [24]

Procedural outcome: COVID-19 impact on physical activity as assessed by 7-item Likert scale

Timepoint [24]

Baseline, week 12, week 26, week 52

Secondary outcome [25]

Procedural outcome: Treatment expectancy as assessed by a 5-point Likert scale (0 = no effect at all; 4 = complete recovery) to the question, what effect do you think the physiotherapy intervention will have on your knee problem?

Timepoint [25]

After first treatment session

Secondary outcome [26]

Procedural outcome: Perceived treatment credibility as assessed by modified 4-item Credibility/Expectancy Questionnaire (CEQ)

Timepoint [26]

After first treatment session

Secondary outcome [27]

Procedural outcome: Intention to exercise via the total score of 3 items (I am committed to engage in physical activity over the next two weeks; I am motivated to engage…; I am determined to engage…), each assessed on a 7-point Likert scale (1 = very strongly disagree; 7 = very strongly agree)

Timepoint [27]

After first treatment session, week 12, week 26, week 52

Secondary outcome [28]

Procedural outcome: Adherence to walking program as assessed by four customised questions.

Timepoint [28]

week 12, week 26, week 52

Secondary outcome [29]

Procedural outcome: Adherence to strengthening program as assessed by four customised questions.

Timepoint [29]

week 12, week 26, week 52

Secondary outcome [30]

Procedural outcome: Therapist beliefs about exercise via Therapist beliefs about exercise questionnaire)

Timepoint [30]

Baseline (pre-trial training) and end of the trial.

Secondary outcome [31]

Procedural outcome: Therapist beliefs about pain via the Pain Attitudes and Beliefs Scale for Physiotherapists

Timepoint [31]

Baseline (pre-trial training) and end of the trial.

Secondary outcome [32]

Procedural outcome: Therapist pain knowledge via the revised Neurophysiology of Pain Questionnaire

Timepoint [32]

Baseline (pre-trial training) and end of the trial.

Secondary outcome [33]

Procedural outcome: Therapist self-rated connection with participant via the Therapist Connectedness Scale

Timepoint [33]

At week 4 (for each participant they treat)

Secondary outcome [34]

Procedural outcome: Therapist perceived intervention credibility via the modified credibility and expectancy questionnaire Connection with participant via the therapist connectedness scale via the revised Neurophysiology of Pain Questionnaire

Timepoint [34]

After pre-trial training (baseline), after the first 8 weeks of treatment with their pilot participant, mid-way through the trial (i.e. halfway through recruitment), at the end of the trial

Secondary outcome [35]

Procedural outcome: Blinding (assessed for participants and treating physiotherapists) as assessed by guesses about group allocation and reasons for guesses

Timepoint [35]

week 52 (participants), end of trial (physiotherapists)

Secondary outcome [36]

Adverse events (in the study knee or elsewhere in the body) measured via customised adverse events questionnaire

Timepoint [36]

week 12, week 26, week 52

Eligibility

Key inclusion criteria

i) Aged greater than or equal to 50 years
ii) Average knee pain intensity of at least 4/10 (overall and/or while walking) over past week using a 0-10 numerical rating scale, where 0 = no pain at all and 10 = worst pain possible
iii) Moderate disability due to the knee over the past week (greater than or equal to 3 on the Global Disability Rating Scale)
iv) Painful knee OA at least 6 months duration that meets the NICE diagnostic criteria for symptomatic knee OA

Minimum age

50 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

i) Conditions that prevent safe participation in physical activity as listed in the American College of Sports Medicine guidelines (e.g., cardiac or lung disease)
ii) Pain in other body areas that currently limits walking ability (e.g., back pain, foot pain, hip pain)
iii) Neurological disorders affecting lower limb movement (e.g., multiple sclerosis, stroke)
iv) Inflammatory arthritis (including rheumatoid arthritis)
v) Fibromyalgia
vi) Previous knee replacement (on painful knee) or planned knee replacement/surgery (next 6 months) or recent knee replacement on the non- or less-painful knee (<6 months)
vii) Previously operated knee is the most painful knee
viii) Intra-articular therapy use in the 12 weeks preceding enrolment
ix) Any condition impacting decision-making/memory (e.g., Alzheimer’s, dementia)
x) Severe depression (>17 on the 4-item PROMIS depression subscale)
xi) Current moderate/vigorous physical activity levels above guideline recommendations (>150 minutes/week; assessed using the Active Australia Physical Activity Questionnaire)
xii) Current purposeful walking for exercise of 30 mins or more per day on 5 or more days per week.
xiii) Unable to commit to study requirements (unable to attend study appointments or complete study outcomes)

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Allocation will be concealed using central automated allocation, with security in place to ensure data cannot be accessed/influenced. It will be stored within an electronic system (REDCap) that will be password-protected (as well as via a hardcopy of the raw randomisation schedule in case the electronic system fails, which will be stored in a secure location). The person who determines if a participant is eligible for inclusion in the trial will be unaware, when this decision is made, to which group the participant will be allocated.

Eligible patients who have provided informed consent will be allocated to the treatment groups by the trial coordinator who will then coordinate treatment appointment scheduling with the appropriate physiotherapist. Only the unblinded trial coordinators (Adelaide, Melbourne) will have access to raw copies of the randomisation schedules.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Participants will be randomly allocated (1:1), using permutated blocks of varying size (4 and 6), and stratified by sex (due to its influence physical activity) and site (South Australia or Victoria). An independent statistician will create the randomisation schedule (using computer generated random numbers).

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Participants will be advised that they will be randomised to receive one of two active physiotherapy treatments that aim to improve overall health (i.e., limited disclosure). We will not disclose the details of group interventions prior to randomisation. After randomisation, participants will be provided only with details of the intervention they will be undertaking. Given that both groups receive active treatment and that we will not disclose the primary outcomes of the trial, we anticipate that this will be sufficient for blinding the participants to group assignment.

The outcome assessor will be a researcher whose role is independent to treatment allocation and delivery, thus will remain blinded to group. Participants will be explicitly instructed not to discuss their treating therapist with the outcome assessor. In-person follow-up assessments will occur at baseline and week 8, and will be performed by the same, blinded assessor at each site. The remaining outcome assessments will be completed by participants independently (i.e. self-reported) via electronic or postal surveys.

Treating therapists will be unavoidably aware of group assignment, but each therapist will be assigned to deliver only one intervention only, and both groups are providing an active intervention. Therapists will not be involved in any outcome assessment.

An independent, blinded statistician will perform data analyses.

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

A total of 198 participants will be recruited (n=99/group). Sample size calculation details have been withheld from the registry to protect trial blinding, but detailed calculations have been provided privately to ANZCTR staff and will be made publically available at the conclusion of the trial.

Primary analysis plan:
The data will be analysed by intention-to-treat and by a statistician blinded to group allocation. We will use linear mixed models with random intercepts for individuals (account for correlation for repeated measures) and will analyse the effect of treatment separately for each outcome. The model will include terms for important prognostic factors, measured prior to randomisation (e.g., sex, age, BMI). We will also include terms for treating therapist and site. Depending on the trial circumstances due to COVID-19, a time-varying covariate for COVID impact may be included (via data derived estimation of COVID impact on the ability to undertake physical activity), as well as a term for treatment mode (e.g., as intended versus telehealth replacing in-person sessions). If necessary, multiple imputation will be used for missing data. We will construct linear contrasts to compare the adjusted mean change in outcome from baseline to each time point between the groups (and 95% confidence interval) to obtain estimates of the effect.

Exploratory mediation analyses:
Using contemporary methodology, we will perform causal mediation analysis to understand the mechanisms by which the intervention of interest works. Details have been withheld from the registry to protect trial blinding, but the proposed analyses have been provided privately to ANZCTR staff and will be made publically available at the conclusion of the trial.

A detailed statistical analysis plan will be published online prior to analysis and unblinding.

Health economic evaluation:
A cost-utility analysis will be undertaken from the perspective of the health system with health related quality of life as assessed by the EQ5D-5L as the main measure of outcome. We will also utilise the primary clinical outcome measures from the trial (WOMAC Total, physical activity levels) as secondary outcome measures for assessing cost effectiveness. Utility-based outcomes generated from application of the EQ5D-5L will be incorporated into the economic analysis to calculate the incremental costs per quality adjusted life year (QALY) gained for the intervention. The resource use items associated with the development and administration of the education intervention including staff time spent in a) the development and provision of face-to-face, evidence-based education sessions and b) development and provision of home activities and weekly development goals, workbook and telephone contacts will be measured and valued using appropriate unit costs. Health service utilisation data for the trial duration including the frequency and duration of hospital in-patient admissions will be accessed from administrative data-sets, and PBS and MBS data will be extracted from Medicare following participant consent. Unit costs will be derived from hospital finance departments, published data sets including PBS and MBS and Refined Diagnosis Related Groups cost weights. Incremental cost effectiveness ratios and their associated confidence intervals will be estimated and cost effectiveness acceptability curves for varying threshold values of cost effectiveness will also be presented. An assessment of the sensitivity of the results obtained to variation in measured resource use, effectiveness and/or unit costs will be undertaken using appropriate one-way and multi-way sensitivity analysis.

A detailed health economic analysis plan will be published online prior to analysis and unblinding.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

2/11/2020

Actual

3/03/2021

Date of last participant enrolment

Anticipated

1/12/2022

Actual

Date of last data collection

Anticipated

1/12/2023

Actual

Sample size

Target

198

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

SA,VIC

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and Medical Research Council (NHMRC)

Address [1]

Level 1, 16 Marcus Clarke Street, Canberra, ACT

Country [1]

Australia

Primary sponsor type

University

Name

The University of South Australia

Address

IIMPACT in Health, Allied Health & Human Performance, G.P.O. Box 2471, Adelaide, South Australia, 5001

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

University of South Australia Human Research Ethics Committee

Ethics committee address [1]

University of South Australia
Ethics and Integrity Services, Human Research Ethics Committee
GPO Box 2471
Adelaide, South Australia 5001
Australia

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

02/07/2019

Approval date [1]

12/09/2019

Ethics approval number [1]

20237

Ethics committee name [2]

Central Adelaide Local Health Network Human Research Ethics Committee

Ethics committee address [2]

North Terrace, Adelaide, SA, 5000

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

16/12/2019

Approval date [2]

06/01/2020

Ethics approval number [2]

12579

Ethics committee name [3]

University of Melbourne Human Research Ethics Committee

Ethics committee address [3]

Alan Gilbert Building, Level 5, 161 Barry Street, Victoria 3010

Ethics committee country [3]

Australia

Date submitted for ethics approval [3]

28/07/2020

Approval date [3]

06/08/2020

Ethics approval number [3]

2057540

Summary

Brief summary

Despite profound health and disease-specific benefits of physical activity, 9 of 10 people with knee osteoarthritis (OA) are inactive. Here we aim to assess the effect of two types of education programs added to an individualised, physiotherapist-led walking and strengthening program to determine if it can improve overall health. Cost-effectiveness of the treatments will be undertaken, as will mediation analyses to consider the mechanistic underpinnings of the treatments.

Using a parallel-group, multicentre randomised controlled trial, participants will be randomised to one of two active treatment groups. Both groups will receive 4 weekly in-person treatment sessions with a physiotherapist, followed by 4 weeks of at-home activities (and weekly check-in by physiotherapist via phone/telehealth), with follow-up sessions at 3 months (via phone/telehealth) and 5 and 9 months (in-person sessions). Primary outcomes are physical activity level (step count via wrist-based accelerometry) and knee symptoms (WOMAC Total score) at 12 months.

Trial website

Trial related presentations / publications

Public notes

An additional 26 pilot participants were recruited to test study processes and to allow for training of the trial physiotherapists. These participants will not be included in the final analysis,

Contacts

Principal investigator

Name

A/Prof Tasha Stanton

Address

The University of South Australia
IIMPACT in Health, Allied Health & Human Performance
G.P.O. Box 2471,
Adelaide, SA
5001

Country

Australia

Phone

+61 883022090

Fax

[email protected]

Contact person for public queries

Name

Dr Felicity Briathwaite

Address

The University of South Australia
IIMPACT in Health, Allied Health & Human Performance
G.P.O. Box 2471,
Adelaide, SA
5001

Country

Australia

Phone

+61450638971

Fax

[email protected]

Contact person for scientific queries

Name

A/Prof Tasha Stanton

Address

The University of South Australia
IIMPACT in Health, Allied Health & Human Performance
G.P.O. Box 2471,
Adelaide, SA
5001

Country

Australia

Phone

+61 883022090

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

All of the individual participant data collected during the trial, after de-identification

When will data be available (start and end dates)?

Immediately following publication, no end date

Available to whom?

Case-by-case basis at the discretion of Primary Sponsor

Available for what types of analyses?

For IPD meta-analyses, etc.

How or where can data be obtained?

Access subject to approvals by Primary Investigator (email contact: [email protected]).

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
9145	Informed consent form					380579-(Uploaded-14-09-2020-13-47-23)-Study-related document.docx

Results publications and other study-related documents

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Trial Review

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