ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12617001524381

Ethics application status

Approved

Date submitted

28/07/2017

Date registered

2/11/2017

Date last updated

6/05/2021

Date data sharing statement initially provided

6/03/2020

Type of registration

Prospectively registered

Titles & IDs

Public title

A randomised trial of colchicine for osteoarthritis of the hand (COLAH)

Scientific title

A randomised trial of colchicine for reducing osteoarthritis-related pain in the hand (COLAH)

Secondary ID [1]

Nill known

Universal Trial Number (UTN)

U1111-1199-9761

Trial acronym

COLAH

Linked study record

N/A

Health condition

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

Hand Osteoarthritis

Condition category

Condition code

Musculoskeletal

Osteoarthritis

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Colchicine , Oral Tablet, 0.5mg, twice daily.
Duration of administration, 12 weeks
To monitor adherence, at the week 6 phone call participants will be asked to count their remaining pills to determine how many have been taken.
All pill packets will be returned at week 12 visit to determine left over pills.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

identical placebo (cellulose) Oral Tablet, twice daily

Control group

Placebo

Outcomes

Primary outcome [1]

VAS pain scores

Timepoint [1]

0 weeks, 6 weeks, 12 weeks and 16 weeks

Secondary outcome [1]

AUSCAN score

Timepoint [1]

0 weeks, 6 weeks, 12 weeks and 16 weeks

Secondary outcome [2]

Ultrasound measured synovitis

Timepoint [2]

0 weeks and 12 weeks

Secondary outcome [3]

Adverse effects (measured by patient report, renal, haematological and hepatic function)

Timepoint [3]

Week 6, Week 12 and Week 16

Secondary outcome [4]

C-reactive protein (from blood samples) at week 0 and week 12

Timepoint [4]

Week 12

Secondary outcome [5]

Grip strength measured by dynamometer at week 0 and week 12.

Timepoint [5]

Week 12

Secondary outcome [6]

Number of tender joints of affected hand at week 0 and week 12

Timepoint [6]

Week 12

Secondary outcome [7]

Number of swollen joints at week 0 and week 12

Timepoint [7]

Week 12

Eligibility

Key inclusion criteria

1) Aged between 40 and 80 years old
2) Men and women with significant hand pain within the last 48 hours (defined as a VAS greater than or equal to 40 mm) with a history of Hand pain for minimum of 6 months.
3) Radiological OA (Kellgren and Lawrence (KL) grade > 1) in > 1 joint
4) Meet American College of Rheumatology (ACR) clinical criteria for hand OA

Minimum age

40 Years

Maximum age

80 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. Concomitant inflammatory rheumatic disease
2. Contraindication to colchicine. This includes renal dysfunction (eGFR <50, abnormal LFT, haematologic condition
3. Chronic glucocorticoid, DMARD or immunosuppressant therapy for arthritis or other indications
4. Women who are pregnant or breast feeding
5. Use of any investigational drug(s) and/or devices within 30 days prior to randomisation
6. Presence of any serious medical illness that may preclude 24 week follow up.
7. Inability to provide informed consent.

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)

Central randomisation by computer at the clinical trial pharmacy

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

Simple randomisation using a randomisation table created by computer software

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes

Intervention assignment

Parallel

Other design features

Phase

Phase 2

Type of endpoint/s

Efficacy

Statistical methods / analysis

An intention-to-treat approach will be taken, consistent with CONSORT guidelines. Baseline characteristics between groups will be analysed by unpaired t test. For the primary endpoint, we will use a random intercept longitudinal regression model over each time point, with the constraint that the baseline means for the two groups are equal. Safety data will be analysed by means of descriptive statistics. Subgroup analysis will be performed for those participants with synovitis identified by ultrasound (exploratory analysis)

Sample Size
The average VAS in a previous RCT of symptomatic hand OA similar to the proposed study was 67.1mm (standard deviation 13.1mm). With 31 in each group, the study will have 80% power to detect a VAS pain difference of 10mm, including projected 10% drop-out rate.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

20/11/2017

Actual

20/03/2018

Date of last participant enrolment

Anticipated

31/12/2018

Actual

10/10/2019

Date of last data collection

Anticipated

30/04/2019

Actual

30/01/2020

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

The Queen Elizabeth Hospital - Woodville

Recruitment postcode(s) [1]

5011 - Woodville

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

The Hospital Research Foundation

Address [1]

60 Woodville Road Woodville, SA 5011

Country [1]

Australia

Primary sponsor type

Individual

Name

Dr Catherine Hill

Address

Rheumatology Clinical Trials
TQEH, Level 5C
28 Woodville Road
Woodville South, SA 5011

Country

Australia

Secondary sponsor category [1]

Charities/Societies/Foundations

Name [1]

Arthritis Australia

Address [1]

Arthritis Australia
Level 2/255 Broadway
GLEBE NSW 2037

Country [1]

Australia

Secondary sponsor category [2]

Charities/Societies/Foundations

Name [2]

The Hospital Research Foundation

Address [2]

60 Woodville Rd, Woodville, SA 5011

Country [2]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

HREC of The Queen Elizabeth Hospital. (TQEH/LMH/MH)

Ethics committee address [1]

The Queen Elizabeth Hospital
Ethics: DX465101
Ground Floor, Basil Hetzel Institute
28 Woodville Road
WOODVILLE SOUTH SA 5011

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

16/11/2016

Approval date [1]

01/06/2017

Ethics approval number [1]

HREC/16/TQEH/261

Summary

Brief summary

BACKGROUND: Osteoarthritis (OA) is the most common joint disease and frequently involves the hand. Painful hand OA is associated with a significant disease burden and reduced quality of life. Indeed, the effect of symptomatic hand OA on quality of life is comparable to rheumatoid arthritis, but affects considerably more people (prevalence ~20% versus ~1% in older adults). With an ageing population, the burden and health-care costs related to hand OA will increase. Patients often rely on NSAIDs or opiates with concomitant adverse effects in this age group to control pain.  Hand OA is a heterogeneous condition with approximately 50% of patients having evidence of synovitis. This phenotype of hand OA with inflammatory signs i.e. those with evidence of synovitis is associated with increased pain. In addition, hand OA joints with synovitis are 3.5 times more likely to experience rapid joint destruction and radiographic progression than those without synovitis. Ultrasound (US) has been shown to reliably detect synovitis in the joints of the hand when performed by an experienced technician. Therefore, this is the subgroup of patients with hand OA that are most in need of evidence-based therapies. Previous study to assess treatments for hand OA using of plaquenil, etanercept or adalimumab found not superior to placebo to alleviate pain. There is possible effect if structural modification with etanercept and adalimumab has been shown to be beneficial in erosive and inflamed hand OA. The cost however of these medications in 20K/per year, therefore there use is an expensive alternative.

Currently, there are no proven pharmacological treatments for hand OA. The lack of categorization of hand OA according to inflammatory phenotype may have contributed to previous negative outcomes in clinical trials.  Cost-effective therapies targeting synovitis may offer a novel approach for reducing disease burden from hand OA. 

Colchicine is a low cost drug which has long been used in the anti-inflammatory treatment of acute gout. There has been recent renewed interest in this ancient drug, particularly its effects in cardiovascular diseases such as pericarditis. The primary mechanism of action of colchicine is tubulin disruption leading to subsequent down-regulation of multiple inflammatory pathways and modulation of innate immunity. Preliminary studies in knee OA have indicated that colchicine may have a beneficial effect on pain and a larger randomized clinical trial of colchicine in knee OA is currently underway.  No studies of colchicine have been undertaken in hand OA. 

STUDY AIMS
Primary hypothesis: 
Colchicine decreases pain (assessed by 100mm VAS) by 10mm more than identical placebo over 12 weeks in patients with clinical hand OA.

STUDY DESIGN
Randomised, placebo-controlled double-blind clinical trial. 
This study will be carried out at The Queen Elizabeth Hospital and Royal Adelaide Hospital.

Trial website

Trial related presentations / publications

Public notes

Attachments [1]

/AnzctrAttachments/372964-Approval Letter - Q20161109 - Hill.pdf (Ethics approval)

Attachments [2]

/AnzctrAttachments/372964-ColchicineprotocolbookTQEH.V3, 30MAY 2017 clean.docx (Protocol)

Attachments [3]

/AnzctrAttachments/372964-COLAH_PICF -V3, 30th MAY 2017_clean.docx (Participant information/consent)

Contacts

Principal investigator

Name

Prof Catherine Hill

Address

TQEH, Level 5C
28 Woodville Rd
Woodville, 5011
South Australia

Country

Australia

Phone

+61 8 8222 6688

Fax

[email protected]

Contact person for public queries

Name

Carlee Ruediger

Address

TQEH, Level 5C
28 Woodville rd
Woodville, 5011
South Australia

Country

Australia

Phone

+61 8 8222 7369

Fax

[email protected]

Contact person for scientific queries

Name

Catherine Hill

Address

TQEH, Level 5C
28 Woodville rd
Woodville, 5011
South Australia

Country

Australia

Phone

+61 8 8222 6688

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 of results, without an end date

Available to whom?

At the discretion of the principle investigator, upon application.

Available for what types of analyses?

This will be assessed on a case by case basis, likely meta-analyses would be acceptable.

How or where can data be obtained?

From the principle investigator upon request.

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
7266	Study protocol					372964-(Uploaded-28-10-2019-14-34-25)-Study-related document.docx

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Colchicine is not effective for reducing osteoarthritic hand pain compared to placebo: A randomised, placebocontrolled trial (COLAH).	2020	https://dx.doi.org/10.1111/imj.14932
Embase	Colchicine is not effective for reducing osteoarthritic hand pain compared to placebo: a randomised, placebo-controlled trial (COLAH).	2021	https://dx.doi.org/10.1016/j.joca.2020.11.002

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically