Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12611001202954
Ethics application status
Approved
Date submitted
1/11/2011
Date registered
23/11/2011
Date last updated
30/11/2018
Date data sharing statement initially provided
30/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A comparison of arthroscopic synovial biopsy based targeted biologic therapy versus conventional therapy in rheumatoid arthritis (RA)
Scientific title
A comparison of arthroscopic synovial biopsy based targeted biologic therapy versus conventional therapy on the time to achieve remission in adults with rheumatoid arthritis (RA)
Secondary ID [1] 273307 0
Nil
Universal Trial Number (UTN)
U1111-1125-5934
Trial acronym
ARBITRATE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 279078 0
Condition category
Condition code
Inflammatory and Immune System 279268 279268 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This trial will randomize patients to either of 2 arms; both arms will have an arthroscopic synovial biopsy at the onset and at 6 months. The arthroscopic synovial biopsy is expected to take around 30 minutes, and will be done with a small bore arthroscopy; the site will of arthroscopy will be a clinically involved joint and the procedure will be done in the operating theatre under an anaesthetic agent (type of anaesthesia as per the anaesthesiologist's preference).

The first arm will be the study group (will commence immediately post synovial biopsy). Participants in this group will receive a biologic disease modifying anti rheumatic drug (bDMARD), either abatacept (T cell co stimulation inhibitor, abatacept administered subcutaneously- 125 mg weekly after a single intravenous dose of ~10 mg/kg ) or a tumor necrosis factor (TNF) inhibitor (adalimumab, subcutaneously 40 mg every other week), depending on the immunohistochemistry of their synovium. The bDMARD will be given for 6 months.

The other arm will be the comparator arm.
Intervention code [1] 283653 0
Treatment: Drugs
Comparator / control treatment
The comparator arm will receive standard combination conventional DMARD therapy (methotrexate, sulfasalazine, hydroxychloroquine with further sequential addition, if indicated, of gold, azathioprine, cyclosporine). Doses (oral): Methotrexate 10 mg/week, Sulfasalazine 500 mg twice a day (increasing to 1g bd over 2 weeks), hydroxychloroquine 200 mg bd; methotrexate dose will be increased if remission not achieved to a maximum dose of 25 mg weekly (and changed to subcutaneous formulation if not tolerated). If necessary, the other drugs will be added to the protocol, if the patient does not achieve remission on this combination.

If after 6 months of conventional therapy, participants have active disease and qualify for PBS (pharmaceutical benefits scheme, Australia) subsidized bDMARDs, they will go on to that bDMARD.

If not eligible at 6 months, patients will be continued on combination DMARD therapy long term.
Control group
Active

Outcomes
Primary outcome [1] 279889 0
Time to achieve remission between the two study arms using composite measures of disease activity: DAS28 (disease activity score using 28 joint count) and ACR (American College of Rheumatology) and EULAR (European League against Rheumatism) response criteria
Timepoint [1] 279889 0
6 months, 12 months
Secondary outcome [1] 294688 0
Indicators of disease activity by clinical assessment, xray at baseline 0, 6, 12 months, MRI (wrist/ hand) at baseline and 6 months.
Timepoint [1] 294688 0
0, 3, 6, 12 months
Secondary outcome [2] 294772 0
Synovial and serum biomarkers predictive of treatment response
Timepoint [2] 294772 0
6 and 12 months
Secondary outcome [3] 294773 0
Adverse events, related to drug toxicity; the events monitored will be generally common for all the oral DMARDs used (except hydroxychloroquine for which visual field testing will be done by the ophthalmology unit at baseline and yearly thereafter). Detailed information sheets will be given to patients, and adverse events for DMARDs will be assessed on basis of symptoms (nausea and vomiting, gastrointestinal symptoms, rash) and abnormal blood counts, renal and liver function tests. In addition for methotrexate and leflunomide, baseline lung function tests will be done, if patients have a history of smoking; these tests may be repeated in case of new and persistent respiratory symptoms (like dry cough and shortness of breath).
Symptoms with DMARDs will lead to withdrawing the offending agents, if not able to be controlled by simple means (for e.g. control of nausea secondary to methotrexate by giving folic acid).

For biologic DMARDs (bDMARDs), serious adverse events (recurrent / serious infections, cancers except non-melanoma skin cancer) will lead to withdrawal of the agent.
Timepoint [3] 294773 0
0. 6. 12 months, as well as monitoring during each follow up visit (except for hydroxychloroquine as mentioned in the secondary outcome box above).

Eligibility
Key inclusion criteria
Anti cyclic citrullinated peptide (CCP) positive active (>/=2 joints) rheumatoid arthritis, duration of disease </=12 months
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previously received DMARD/ bDMARD for RA; ANA positive >320, hepatitis B/ C/ HIV positivity, concomitant treatment with experimental drug

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)
Simple randomisation by using a randomisation table created by computer software (computerised sequence generation by a statistician offsite). The person who determined if a subject was eligible for inclusion in the trial will be unaware, when this decision was made, to which group the subject would be allocated.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by using a randomisation table created by computer software (computerised sequence generation).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/11/2011
Actual
17/04/2012
Date of last participant enrolment
Anticipated
29/07/2020
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
104
Accrual to date
67
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment postcode(s) [1] 4678 0
5000
Recruitment postcode(s) [2] 24976 0
5042 - Bedford Park
Recruitment postcode(s) [3] 24977 0
5046 - Oaklands Park

Funding & Sponsors
Funding source category [1] 284172 0
Self funded/Unfunded
Name [1] 284172 0
Country [1] 284172 0
Australia
Primary sponsor type
Individual
Name
Professor Malcolm D Smith
Address
Rheumatology Unit, Flinders Medical Centre, Bedford Park SA 5042
Country
Australia
Secondary sponsor category [1] 269097 0
Individual
Name [1] 269097 0
Dr Mihir D Wechalekar
Address [1] 269097 0
Rheumatology Unit, Flinders Medical Centre, Bedford Park SA 5042
Country [1] 269097 0
Australia
Secondary sponsor category [2] 269098 0
Individual
Name [2] 269098 0
Dr Jennifer Walker
Address [2] 269098 0
Rheumatology Unit, Flinders Medical Centre, Bedford Park SA 5042
Country [2] 269098 0
Australia
Secondary sponsor category [3] 269099 0
Individual
Name [3] 269099 0
A/ Prof Susanna Proudman
Address [3] 269099 0
Rheumatology Unit, Royal Adelaide Hospital, Port Rd, Adelaide SA 5000
Country [3] 269099 0
Australia
Secondary sponsor category [4] 269100 0
Individual
Name [4] 269100 0
Prof John Slavotinek
Address [4] 269100 0
Medical Imaging
Flinders Medical Centre
Bedford Park SA 5042
Country [4] 269100 0
Australia
Secondary sponsor category [5] 269101 0
Individual
Name [5] 269101 0
A/Prof Michael Ahern
Address [5] 269101 0
Rheumatology Unit, Flinders Medical Centre, Bedford Park SA 5042
Country [5] 269101 0
Australia
Secondary sponsor category [6] 288307 0
Individual
Name [6] 288307 0
Professor Leslie G Cleland
Address [6] 288307 0
Rheumatology Unit, Royal Adelaide Hospital, Port Rd, Adelaide SA 5000
Country [6] 288307 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 272097 0
Flinders Medical Centre Ethics Committee
Ethics committee address [1] 272097 0
Southern Adelaide Clinical Human Research Ethics Committee
SA Local Health Network
Room 2A221 - Inside Human Resources
Flinders Medical Centre, Bedford Park SA 5042
Ethics committee country [1] 272097 0
Australia
Date submitted for ethics approval [1] 272097 0
Approval date [1] 272097 0
20/09/2011
Ethics approval number [1] 272097 0
1/10/0199
Ethics committee name [2] 272098 0
Royal Adelaide Hospital Ethics Committee
Ethics committee address [2] 272098 0
Research Ethics Committee
Royal Adelaide Hospital
Level 3 Hanson Institute
Royal Adelaide Hospital
North Terrace, Adelaide SA 5000
Ethics committee country [2] 272098 0
Australia
Date submitted for ethics approval [2] 272098 0
Approval date [2] 272098 0
07/10/2011
Ethics approval number [2] 272098 0
100911b

Summary
Brief summary
The aim of this study is to investigate if the treatment of rheumatoid arthritis (RA) based on the results of analysis of a biopsy of the involved joint lining is better than usual therapy (not based on the results of biopsy).
The way standard care or bDMARD therapy will be chosen will be by the process called randomization (which will happen only once at the beginning of the study), which essentially is the equivalent of tossing a coin and deciding the treatment option on the basis of the result. This gives equal chance of going to either the bDMARD or standard care treatment arm. Once the patient has chosen to participate, they will receive an arthroscopic biopsy from the lining of an inflamed joint (called the synovium). The bDMARD will be chosen on the basis of the biopsy.
Trial website
Nil
Trial related presentations / publications
Nil
Public notes

Contacts
Principal investigator
Name 33338 0
Prof Professor Malcolm D Smith
Address 33338 0
Rheumatology Unit, Flinders Medical Centre, Bedford Park SA 5042
Country 33338 0
Australia
Phone 33338 0
+61882046429
Fax 33338 0
+61882044150
Email 33338 0
[email protected]
Contact person for public queries
Name 16585 0
Dr Mihir D Wechalekar
Address 16585 0
Rheumatology Unit, Flinders Medical Centre, Bedford Park SA 5042
Country 16585 0
Australia
Phone 16585 0
+61882046429
Fax 16585 0
+61882044150
Email 16585 0
[email protected]
Contact person for scientific queries
Name 7513 0
Dr Mihir D Wechalekar
Address 7513 0
Rheumatology Unit, Flinders Medical Centre, Bedford Park SA 5042
Country 7513 0
Australia
Phone 7513 0
+61882046429
Fax 7513 0
+61882044150
Email 7513 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


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
SourceTitleYear of PublicationDOI
EmbaseImmune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression.2018https://dx.doi.org/10.1371/journal.pone.0192704
N.B. These documents automatically identified may not have been verified by the study sponsor.