Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000732987
Ethics application status
Approved
Date submitted
18/05/2020
Date registered
13/07/2020
Date last updated
23/09/2020
Date data sharing statement initially provided
13/07/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of hyaluronic acid injections into the base of thumb joint on pain and function for osteoarthritis
Scientific title
Effectiveness of intra-articular hyaluronic acid compared to corticosteroid or placebo injections to treat basal thumb osteoarthritis: a prospective, randomised, blinded clinical study
Secondary ID [1] 301301 0
Nil known
Universal Trial Number (UTN)
U1111-1252-1589
Trial acronym
HAITOA
Linked study record
Nil

Health condition
Health condition(s) or problem(s) studied:
osteoarthritis 317487 0
Condition category
Condition code
Musculoskeletal 315589 315589 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention requires an intra-articular injection of one of 3 randomised substances to the participant's carpometacarpal joint with the goal to examine which intervention is the most effective at reducing pain and improving function after a single injection.
Participants will initially receive 2ml of 2% lignocaine injected subcutaneously at the injection site at least four minutes prior to intervention. Participants will be randomised in equal proportions between the following three treatment options: a single 1ml injection of 8mg hyaluronic acid (arm 1), a single 1ml injection of 40mg methylprednisolone acetate (arm 2) or a single 1ml injection of sterile saline (arm 3) which will be injected intra-articularly to the first carpometacarpal joint of the affected hand using radiological guidance with a mini c-arm. The injections will be performed by one of two hand surgeons at Plastic Surgery Victoria.
Participants will also be given a "pain killer diary" to record their use of analgesia in the 2 weeks prior to and 6 months after their intervention. This diary will be viewed at every visit to monitor adherence.
Intervention code [1] 317605 0
Treatment: Devices
Intervention code [2] 317717 0
Treatment: Drugs
Comparator / control treatment
The control treatments for this study are methylprednisolone acetate 40mg in 1ml and normal saline 40mg in 1ml. The methylprednisolone acetate is an active control. Normal saline is a placebo control.
Control group
Active

Outcomes
Primary outcome [1] 323823 0
Change in pain of the affected hand as measured by the Visual Analogue Scale.
Timepoint [1] 323823 0
Outcomes will be assessed pre-intervention (on the day of intervention) and at 2, 4, 12 and 26 weeks (primary endpoint) post intervention.
Primary outcome [2] 323824 0
Patient Global Assessment score measuring function, pain and disability
Timepoint [2] 323824 0
Outcomes will be assessed pre-intervention (on the day of intervention) and at 2, 4, 12 and 26 weeks (primary endpoint) post intervention.
Primary outcome [3] 323825 0
Disease Activity Assessment score
Timepoint [3] 323825 0
Outcomes will be assessed pre-intervention (on the day of intervention) and at 2, 4, 12 and 26 weeks (primary endpoint) post intervention.
Secondary outcome [1] 382997 0
Pinch and grip strength measured with a hand dynamometer (composite primary outcome)
Timepoint [1] 382997 0
Outcomes will be assessed pre-intervention (on the day of intervention) and at 2, 4, 12 and 26 weeks (primary endpoint) post intervention.
Secondary outcome [2] 382998 0
The secondary outcome of adverse events recorded for each treatment arm including rash, oedema, blisters, lymphadenopathy (at elbow or axilla of affected side), septic arthritis and anaphylaxis)
Timepoint [2] 382998 0
At any point during the study from intervention to 26 weeks post intervention as self reported by participant or discovered during clinical examination at intervention, and at 2, 4, 12 and 26 weeks (secondary endpoint) post intervention.
Secondary outcome [3] 383456 0
First carpometacarpal joint range of motion measured with a goniometer (primary outcome)
Timepoint [3] 383456 0
Outcomes will be assessed pre-intervention (on the day of intervention) and at 2, 4, 12 and 26 weeks (primary endpoint) post intervention.
Secondary outcome [4] 383986 0
Change in use of analgesia as measured by patients' "pain killer diary" (primary outcome)
Timepoint [4] 383986 0
The "pain killer diary" will be completed for 2 weeks pre-intervention until 26 weeks after intervention.

Eligibility
Key inclusion criteria
Participants eligible for the trial must comply with all of the following at randomization:
1. Age greater or equal to 40 years
2. Symptomatic 1st carpometacarpal osteoarthritis requiring non-operative treatment, diagnosed by both standard clinical and radiographic measures as below
a. Clinical osteoarthritis includes the following
i. History of carpometacarpal tenderness, thumb or wrist pain at rest or with activity, joint stiffness or decreased function
ii. Examination yielding dorsoradial prominence of the thumb metacarpal base, tenderness over the joint, crepitus, positive “grind” test or positive “distraction” test
b. Radiographic evidence of osteoarthritis of any Eaton-Littler-Burton classification

Patients who have received previous injections to the carpometacarpal joint to be treated of either hyaluronic acid or steroid will be included if they have had 1 or 2 prior injections with reported improvement in pain and function after the injections as they will be likely to have benefit from a further injection.
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prior surgery to affected thumb/wrist
2. Injury to joint in last 6 months
3. Prior or current infection in affected joint
4. History of inflammatory arthritis or skin disease at the injection site
5. Pre-existing chondrocalcinosis, thoracic outlet syndrome, carpal tunnel syndrome, Guyon’s canal syndrome, cubital tunnel syndrome, diabetic neuropathy or cheiroarthropathy, palmar tenosynovitis, trigger thumb, fibromyalgia, pain syndrome, psoriasis
6. Pregnant or lactating women
7. Known allergy to local anaesthetic, cortisone or hyaluronic acid derivative products
8. Visual Analogue Scale <40mm
9. Regular opiate use for a concomitant condition or analgesics unless stable dosage for over or equal to 1 month
10. If participants have had more than 2 injections of either hyaluronic acid or corticosteroid to the first carpometacarpal joint or an injection in the last 6 months.

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)
Participants will be randomly assigned to either control, corticosteroid injection or hyaluronic acid injection with a 1:1:1 allocation as per a computer generated randomisation schedule.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The study statistician will generate the treatment list using randomisation function in STATA by a random number generator which will allocate participants by order of consenting to the three treatment groups. The statistician will not refer again to the list until all data analysis is complete.
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
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The hyaluronic acid arm will be compared with the methylprednisolone acetate and normal saline arms for all primary analysis.
The collected data will be entered into and stored in the REDCap program using a custom designed project structure. It will be exported into an excel spreadsheet and loaded into Stata IC (StataCorp, College Station, Texas, USA) for statistical comparison.
Statistical analysis will be carried out by the Department of Surgery Research Co-ordinator.
Continuous data distribution will be determined by Shapiro Wilks test for normality. This is important in determining what type of comparative statistical test may be appropriate and how data should be described or presented. Comparisons will use appropriate tests: t-tests or ANOVAs (parametric) or Wilcoxon-Mann Whitney or Kruskal Wallis (non-parametric) depending on nature of data and its distribution. Two-sided statistical tests will be used and reported. The data may also be assessed by regression analysis or a specialised form of regression analysis: generalized linear mixed models. The latter are very useful for analysis of biological data as it can be applied to normal and non-normal data and are especially useful when data structure is complex and not normally distributed for which there are very few tests, and when data transformation fails to bring data to a normal distribution without skewness or kurtosis problems. In this study, for example there will be comparison of multiple data points for each participant to be compared across treatment arms. It also allows us to test for effect of modifiers such as whether the participant is male or female or if they have had previous treatment, what type, what frequency, severity of pre-treatment disease and so on. These are all important to understand as whether they have any predictive value in the outcome, as these may then be highlighted when presenting or publishing the research results as part of the decision-making process in whether or not to use this treatment for different patients (medical treatment algorithm).
Categorical data will be presented as percentage frequency and assessed using chi-square or Fisher’s exact tests or the generalized linear mixed models using appropriate family and link functions to work with categorical data.
Statistical significance will require P values less than or equal to 0.05.
For presentation, data will be shown in either in tables or graphs. Continuous data will be presented as either mean ± standard deviation (normal distribution) or median & range (min, max; non-normal distribution) in either bar graphs or in tables. Categorical data will be presented as percent frequency & samples size as either bar graphs or in tables.
For comparisons, the output of paired t-tests and repeated measures ANOVAs and their equivalents for non-normally distributed data will be reported as the output of the test (ie t or Z value) and the p-value. The output of regression or generalised linear mixed model analysis will be described as either regression co-efficient or odds ratios, and 95% confidence intervals and p values.
The numbers of any missing data will be assessed and reported.
Please note, that data found to be outliers compared to other data from the same treatment group can be identified and removed from further analysis. However, after identifying but before removing, the data accuracy will be checked if possible (referring to original data collection if not directly into REDCap. If data is to be removed from further analysis, the number and identity of outlier data will be recorded and reported. Outliers are usually assessed as values falling outside of the interquartile range of values. A mixture of graphics (box plots) and coding in STATA will be used to assess and identify any outlier data. Any data removed will not be replaced but treated as missing data. The choice of statistical test will also be sensitive to whether or not there is missing data.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
5/10/2020
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
90
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 16692 0
Frankston Hospital - Frankston
Recruitment hospital [2] 16693 0
Peninsula Private Hospital - Frankston - Frankston
Recruitment postcode(s) [1] 30291 0
3199 - Frankston

Funding & Sponsors
Funding source category [1] 305743 0
Self funded/Unfunded
Name [1] 305743 0
Country [1] 305743 0
Primary sponsor type
Individual
Name
Prof. Warren Rozen
Address
Plastic Surgery Victoria
Suite 17
Peninsula Private Hospital
525 McClelland Drive
Langwarrin 3910
Victoria
Country
Australia
Secondary sponsor category [1] 306195 0
None
Name [1] 306195 0
None
Address [1] 306195 0
None
Country [1] 306195 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306018 0
Monash Health Human Research Ethics Committee
Ethics committee address [1] 306018 0
Ethics committee country [1] 306018 0
Australia
Date submitted for ethics approval [1] 306018 0
06/05/2020
Approval date [1] 306018 0
28/07/2020
Ethics approval number [1] 306018 0
RES-20-0000-280A

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 102438 0
Prof David Hunter-Smith
Address 102438 0
Frankston Hospital
2 Hastings Road
Frankston 3199
Victoria
Country 102438 0
Australia
Phone 102438 0
+61 409787500
Fax 102438 0
Email 102438 0
[email protected]
Contact person for public queries
Name 102439 0
Lisa Ellis
Address 102439 0
Frankston Hospital
2 Hastings Road
Frankston 3199
Victoria
Country 102439 0
Australia
Phone 102439 0
+61 433394331
Fax 102439 0
Email 102439 0
[email protected]
Contact person for scientific queries
Name 102440 0
Lisa Ellis
Address 102440 0
Frankston Hospital
2 Hastings Road
Frankston 3199
Victoria
Country 102440 0
Australia
Phone 102440 0
+61 433394331
Fax 102440 0
Email 102440 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Patients details will be kept strictly confidential and results will be presented as pooled data in a de-identified fashion


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.