Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000398808
Ethics application status
Approved
Date submitted
24/02/2021
Date registered
9/04/2021
Date last updated
16/11/2023
Date data sharing statement initially provided
9/04/2021
Date results information initially provided
16/11/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Frequency of manual therapy for individuals with knee osteoarthritis: The Opti-OK Trial
Scientific title
Does the frequency of manual therapy improve clinical outcomes for individuals aged over 45 years with knee osteoarthritis : The Opti-OK Trial?
Secondary ID [1] 303543 0
None
Universal Trial Number (UTN)
U1111-1265-3200
Trial acronym
Linked study record
ACTRN12616000337471p

This was the feasibility trial for the current study

Health condition
Health condition(s) or problem(s) studied:
Knee osteoarthritis 320890 0
Condition category
Condition code
Musculoskeletal 318706 318706 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: Manual therapy involving passive accessory movements, passive physiological movements, and mobilisations with movement, applied to the tibio-femoral, patello-femoral and superior tibio-fibular joints. Forces applied and number of repetitions will be decided by the physiotherapist, aiming to alter joint structures while accounting for the tolerance of individual participants. The pain response of the participant will guide these decisions. At the final (sixth) treatment session every participant will receive exercise therapy, advice and education on managing their osteoarthritis. A multi-modal exercise programme including range of motion, strengthening, aerobic and co-ordination exercises,will be individually tailored to each participant using variations in amount of resistance, and number of exercise repetitions. The aim is to challenge the participant and fatigue the muscles, in order to produce a treatment effect. The exercise programme and education/advice will also be provided in written format. The treatment will be provided by New Zealand registered physiotherapists, at a frequency of twice per week for three weeks. Each session will be of 45 minutes duration. The intervention will be provided in University Physiotherapy Clinics or Physiotherapy Private Practices.
Arm 2: As for Arm 1 but provided at a frequency of once per week for six weeks. Each session will be of 45 minutes duration.
Adherence to compliance with the allocated treatment frequency will be reported by reviewing the electronic attendance record. Fidelity to treatment protocols will be monitored by random audit of participant notes, and observation of at least two treatment sessions per trial physiotherapist, conducted by the Primary Investigator (CC).
Intervention code [1] 319827 0
Treatment: Other
Intervention code [2] 319828 0
Lifestyle
Comparator / control treatment
Arm 3 - participants will attend for one treatment session with a New Zealand registered physiotherapist, in a University Physiotherapy Clinic, or a Physiotherapy Private Practice. This will be of 45 minutes duration. Participants will receive an individually tailored exercise programme, education and advice about how to manage their osteoarthritis. A multi-modal exercise programme including range of motion, strengthening, aerobic and co-ordination exercises, will be individually tailored to each participant using variations in amount of resistance, and number of exercise repetitions. The aim is to challenge the participant and fatigue the muscles, in order to produce a treatment effect. The exercise programme and education/advice will also be provided in written format. Exercises will include quadriceps and hamstrings strengthening exercises, knee flexion and extension range of motion exercises, stretches for quadriceps/hamstrings/gastrocnemius muscles, neuromuscular coordination exercises such as weaving through cones, step-ups, and sit-to-stand exercises.
Control group
Active

Outcomes
Primary outcome [1] 326637 0
Function using the function/daily living subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS)
Timepoint [1] 326637 0
4-weeks and 7-weeks after intervention starts, and 6-months (primary timepoint) from randomisation
Secondary outcome [1] 392228 0
Knee pain using the pain subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS)
Timepoint [1] 392228 0
4-weeks and 7-weeks after intervention starts, and 6-months from randomisation
Secondary outcome [2] 392229 0
Quality of life using the quality of life subscale of the KOOS
Timepoint [2] 392229 0
4-weeks and 7-weeks after intervention starts, and 6-months from randomisation
Secondary outcome [3] 392230 0
Physical performance measure (PPM) 30-second sit-to-stand
Timepoint [3] 392230 0
4-weeks and 7-weeks after intervention starts, and 6-months from randomisation
Secondary outcome [4] 392231 0
PPM - timed stair climb
Timepoint [4] 392231 0
4-weeks and 7-weeks after intervention starts, and 6-months from randomisation
Secondary outcome [5] 392232 0
PPM - a timed 40 metre self-paced walk
Timepoint [5] 392232 0
4-weeks and 7-weeks after intervention starts, and 6-months from randomisation
Secondary outcome [6] 392233 0
Knee range of motion measured with a goniometer
Timepoint [6] 392233 0
4-weeks and 7-weeks after intervention starts, and 6-months from randomisation
Secondary outcome [7] 392234 0
Participant global; rating of change (GROC)
Timepoint [7] 392234 0
4-weeks and 7-weeks after intervention starts, and 6-months from randomisation
Secondary outcome [8] 392235 0
Quality of life using the EuroQOL (EQ-5D-5L)
Timepoint [8] 392235 0
6-months from randomisation
Secondary outcome [9] 392236 0
Costs and resource use will be collected using a costs questionnaire, which incorporates the Osteoarthritis Costs and Consequences Questionnaire (OCC-Q) and the EQ-5D-5L
Timepoint [9] 392236 0
6-months from randomisation
Secondary outcome [10] 392237 0
For Arms 1 and 2: Participant rated need for further treatment, with question "If you were not enrolled in this clinical trial, would you consider your knee good enough to be discharged from physiotherapy?"
Timepoint [10] 392237 0
At each follow-up treatment session (5 times)
Secondary outcome [11] 392238 0
For Arms 1 and 2: Physiotherapist rated need for further treatment with the question ""If the participant was not enrolled in this clinical trial, would you consider their knee good enough to be discharged from physiotherapy?"
Timepoint [11] 392238 0
At each follow-up treatment session (5 times)

Eligibility
Key inclusion criteria
Adults (45yrs or older) with persistent knee pain (pain on most days in the last month)
Clinical classification criteria for knee OA (American College of Rheumatology): persistent knee pain plus 3 of the following: morning knee stiffness that eases within 30 mins; no heat/effusion; bony enlargement; pain on palpation; crepitus; age 50 years or over.
In addition, the nominated knee must lack full extension (at least 5 degrees loss of movement).
Minimum age
45 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previous lower limb joint arthroplasty, lower limb surgery in previous 12 months, significant injury (requiring medical specialist treatment) to lower limb in previous 12 months, a course of conservative management for knee OA in previous 12 months, consultation with orthopaedic/rheumatology specialist for OA, on waiting list for knee surgery, commencement of new medication for OA (previous 1 month); knee joint injection in previous 3 months; other forms of arthritis particularly inflammatory disease such as rheumatoid arthritis, plus comorbidities that will preclude safe application of manual or exercise therapy e.g. severe osteoporosis, uncontrolled hypertension.

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)
Randomisation will be conducted by the clinical trial coordinator. It will be done using randomly generated identification numbers and allocation using opaque sealed envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be stratified by ethnicity to ensure equal and representative numbers of Maori are included in each arm of the trial.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size: Total sample size was calculated as 180 (60 in each group). A minimal clinically important difference (MCID) of ten points on the KOOS was used as the effect size and 15 points as the standard deviation (SD). We selected a level of 90% power to detect a significant difference (p< 0.05) in the main outcome measures. The estimated total sample size was increased to allow for an approximated 15% dropout rate and missing data, based on a 13% dropout rate in the feasibility study.

Descriptive statistics will be used to present baseline characteristics of study participants.

Primary Analysis.
Analysis will be conducted on a modified intention to treat basis (using all available data and multiple imputation to replace missing values). Tests will be two-sided and significance level set at 5%.
Linear mixed models will be used to detect between group differences for the outcomes at six months, and to evaluate between group differences at multiple time points. Additionally, Arms 1 & 2 will be combined to compare manual therapy with no manual therapy. The Bonferroni calculation will be used to adjust for multiple comparisons. Non- normal distribution of data will be transformed initially, followed by bootstrapping techniques.
Secondary Analysis.
OMERACT-OARSI responder criteria that combine information on pain, function and patient assessment of change, will be used to identify numbers of responders to treatment at six months, and between group differences will be compared using logistic regression, reporting odds ratios.
All analyses will be adjusted for known confounders in knee OA studies of age, gender and BMI.
Economic analysis
QALYs will be calculated by applying NZ general population utility weights to the EQ-5D . Gains in QALYs from baseline to six months will be reported. Total costs will be calculated by using data acquired from the OCC-Q and valuing these using national standardized valuations. Incremental Cost Utility Ratios (ICUR) will be calculated by dividing the difference in healthcare costs between groups by the difference in QALYs between groups, giving an indication of value for money.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
26/04/2021
Actual
28/05/2021
Date of last participant enrolment
Anticipated
22/10/2021
Actual
3/11/2022
Date of last data collection
Anticipated
22/04/2022
Actual
27/04/2023
Sample size
Target
180
Accrual to date
Final
154
Recruitment outside Australia
Country [1] 23486 0
New Zealand
State/province [1] 23486 0
Otago, Southland

Funding & Sponsors
Funding source category [1] 307967 0
Other
Name [1] 307967 0
The Stanley Paris Research Fellowship, University of Otago Alumni Office
Country [1] 307967 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
Centre for Innovation, Level 1 (East Wing), 87 St David St, Dunedin 9054, New Zealand
Country
New Zealand
Secondary sponsor category [1] 308683 0
None
Name [1] 308683 0
Address [1] 308683 0
Country [1] 308683 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307961 0
Southern Health and Disability Ethics Committee (New Zealand)
Ethics committee address [1] 307961 0
PO Box 5013
Wellington 6140
Ethics committee country [1] 307961 0
New Zealand
Date submitted for ethics approval [1] 307961 0
23/03/2021
Approval date [1] 307961 0
29/04/2021
Ethics approval number [1] 307961 0
21/STH/81

Summary
Brief summary
Manual therapy is an effective intervention for treatment of people with knee osteoarthritis (OA). However, the optimal treatment dose has yet to be defined. Dose is a well-recognised aspect of any treatment approach and is known to affect clinical outcomes. For example in the fields of medication or radiation therapy it would be unheard of not to prescribe a dose of treatment. Surprisingly, it has been scarcely investigated for manual therapy. Existing studies of manual therapy for knee OA show many differences in the frequency of treatment, varying from once to twice or three times per week. There are no rationales provided in any previous studies for the selection of treatment frequency, which may be due to uncertainty about the mechanisms of action of manual therapy. Variation in provision of treatment makes it difficult to directly compare results from different studies, or for physiotherapists to translate findings into clinical practice. Therefore there is a clear need for research to investigate the optimal dose of manual therapy for people with knee OA.
This research will investigate whether frequency of treatment with manual therapy for people with knee OA affects clinical outcomes at 6-month follow-up. In a fully-powered, 3-arm, clinical randomised controlled trial (RCT), participants receiving six manual therapy treatments at a frequency of twice per week will be compared to those receiving six treatments at a frequency of once per week, compared to a control group with best-practice usual care. Furthermore an economic analysis will evaluate if the interventions are cost-effective and value for money.
Findings from the OPTi-OK (Optimisation of Physiotherapy Treatment in Knee Osteoarthritis) RCT will provide practical information about delivery of care that will promote rapid translation into physiotherapy practice.
Trial website
www.otago.ac.nz/kneeoa

This will become active when ethics has been obtained and recruitment starts
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 109054 0
Dr Cathy Chapple
Address 109054 0
School of Physiotherapy
University of Otago
325 Great King Street
Dunedin 9016
Country 109054 0
New Zealand
Phone 109054 0
+64 0276811228
Fax 109054 0
Email 109054 0
[email protected]
Contact person for public queries
Name 109055 0
Dr Cathy Chapple
Address 109055 0
School of Physiotherapy
University of Otago
325 Great King Street
Dunedin 9016
Country 109055 0
New Zealand
Phone 109055 0
+64 0276811228
Fax 109055 0
Email 109055 0
[email protected]
Contact person for scientific queries
Name 109056 0
Dr Cathy Chapple
Address 109056 0
School of Physiotherapy
University of Otago
325 Great King Street
Dunedin 9016
Country 109056 0
New Zealand
Phone 109056 0
+64 0276811228
Fax 109056 0
Email 109056 0
[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?
De-identified patient demographic data and outcomes data
When will data be available (start and end dates)?
After data collection complete for 5 years. 28/04/2022 - 28/04/2027
Available to whom?
Other researchers for IPD meta-analyses who have gained ethical approval for their research
Available for what types of analyses?
IPD meta-analyses
How or where can data be obtained?
Via email from the PI Dr Cathy Chapple
[email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
10793Study protocol  [email protected] The research team is planning to publish the study... [More Details]
10794Other    A manual of trial interventions will be put togeth... [More Details]



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Plain language summaryNo Results not available yet

Documents added automatically
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