Hydroxychloroquine (HCQ) in patients with inflammatory osteoarthritis (OA) of the hands

ISRCTN ISRCTN46445413
DOI https://doi.org/10.1186/ISRCTN46445413
EudraCT/CTIS number 2011-001689-16
Secondary identifying numbers 2011 05 30-1
Submission date
10/05/2011
Registration date
09/06/2011
Last edited
19/05/2022
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Musculoskeletal Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Gerd - R. Burmester
Scientific

Charité - University of Medicine, Berlin
Department of Rheumatology and Clinical Immunology
Charitéplatz 1
Berlin
10117
Germany

Study information

Study designInterventional randomised placebo-controlled double-blind multicentre study
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleProspective, randomised, double-blind, placebo-controlled clinical trial with hydroxychloroquine (HCQ) in patients with inflammatory osteoarthritis (OA) of the hands
Study acronymOA Treat
Study objectivesOsteoarthritis (OA) is a heterogeneous group of conditions with a disturbed integrity of articular cartilage and changes in the underlying bone. The pathogenesis of OA is multifactorial and involves a complex interplay of genetic, metabolic, biochemical, and biomechanical factors with variable components of inflammation. The disease, as one of the most prevalent musculoskeletal diseases, leads to pain in and around the affected joints and to swelling, stiffness, deformity, and gradual loss of function. It is not just a disease of elderly people, but also affects the younger working age population. Hydroxychloroquine (HCQ) is a disease modifying anti-rheumatic drug (DMARD) that in clinical practice is also used for inflammatory OA and has been employed for the treatment of various rheumatic and dermatologic diseases. Current research has further enhanced our understanding of the pharmacologic mechanisms of action of these drugs involving inhibition of endosomal toll - like receptor (TLR) signalling, which limits B cells and dendritic cell activation. Three studies of HCQ in OA, including one abstract and one letter are available. Most studies show that currently a wide variety of outcome measures are used in rather small patient populations.

Despite initial indications for a good effect of HCQ, there has been no randomized, double-blind, and placebo-controlled trial in a larger patient group. In the European League Against Rheumatism (EULAR) evidence based recommendations for the management of hand OA HCQ was not included as a therapeutic option, apparently because of the currently missing randomized clinical trials. The aim of the proposed study is to investigate the efficacy of HCQ by clinical and radiological outcome compared to placebo in patients with severe and refractory inflammatory hand OA.
Ethics approval(s)Approved as of 17/04/2013
Health condition(s) or problem(s) studiedRefractory inflammatory hand osteoarthritis
InterventionArm 1:
1. Capsules body weight adapted to pharmaceutical package (30 - 49 kg one capsule with 200 mg HCQ as daily single dose
2. 50 – 64 kg one capsule with 200 mg HCQ as single dose on day 1 and two capsules with 200 mg HCQ as single dose on day 2
3. > 65 kg two capsules with 200 mg HCQ as single dose

Arm 2:
One capsule with oral placebo application characteristics
Intervention typeDrug
Pharmaceutical study type(s)
PhasePhase III
Drug / device / biological / vaccine name(s)Hydroxychloroquine
Primary outcome measure1. Australian-Canadian OA Index (AUSCAN, German version) for pain, and hand disability as co-primary clinical outcome at week 52
2. Radiographic co-primary endpoint: Radiographic progression assessed by the Kallman Score at week 52
Secondary outcome measures1. Efficacy of HCQ with respect to AUSCAN at week 26 to patient’s global assessment of disease activity, patient’s assessment of stiffness, and physician’s global assessment of disease activity at week 26, 52
2. To compare pain, functioning, disability, quality of life, patient-acceptable symptoms and health (HAQ, SF-36, SACRAH, FiHOA, AUSCAN, Backman score, etc.) week 0, 26, 52
3. To assess and to compare the inflammatory status using the following parameters: joint pain and joint swelling, night pain, morning stiffness, local erythema/redness, CRP - and ESR - levels from baseline to week 26, 52
4. To compare cumulative dosage of consumption per week of standard therapy (NSAIDs, COXibs)
5. Assessment of safety: Safety and tolerability of HCQ with reports on adverse event (AE) and serious advere event (SAE)
6. The eye examination will be performed by an ophthalmologist (baseline and every 6 months)
Overall study start date04/12/2011
Completion date05/07/2018

Eligibility

Participant type(s)Patient
Age groupAdult
SexBoth
Target number of participants510
Key inclusion criteria1. Men and women from 40 to 80 years
2. Presence of clinical hand OA according to American College of Rheumatology (ACR) criteria
3. Conforming to the ACR criteria for hand OA with recent X ray, dating less than 6 months ago, X ray of the hands showing radiological signs of digital OA in one or more joints as defined by grades 2 or higher, per Kellgren and Lawrence scale or alternatively using the Kallman method or alternativly using the Verbruggen Score;
4. Symptomatic digital OA with more than three finger joints for more than 3 months (at least every other day) despite taking analgesics and non-steroidal anti-inflammatory drugs (NSAIDs)
5. Pain above 35 mm as evaluated by the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) -Visual Analogue Scale( VAS) (0 - 100 mm)
6. Function as co-primary clinical outcome with ≥ 9 using the AUSCAN LK function subscale, or ≥ 225 F (out of maximum of 800) on the AUSCAN VA function subscale
Key exclusion criteria1. Patients who have already been treated with HCQ
2. Existence of painful syndrome of upper limbs likely to interfere with the monitoring of pain
3. Patients suffering or having suffered from secondary OA after one of the following diseases (e.g. infectious arthritis, acromegaly, ochronosis, haemochromatosis, gout, etc.) or inflammatory joint diseases
4. Any unstable medical condition which would put the patient at an unacceptable risk
5. Planned Surgery
6. Local injection with glucocorticoids or other medications within the previous three months
7. Oral glucocorticoids
8. Presence of retinopathy
Date of first enrolment04/12/2011
Date of final enrolment31/12/2015

Locations

Countries of recruitment

  • Germany

Study participating centre

Charité - University of Medicine, Berlin
Berlin
10117
Germany

Sponsor information

Charité - University of Medicine, Berlin (Germany)
University/education

c/o Prof. Gerd-R. Burmester
Department of Rheumatology and Clinical Immunology
Charitéplatz 1
Berlin
10117
Germany

Phone +49 (0)30 450 513 061
Email gerd.burmester@charite.de
Website http://rheumatologie.charite.de
ROR logo "ROR" https://ror.org/001w7jn25

Funders

Funder type

Government

German Federal Ministry of Education and Research (Bundesministerium Fur Bildung und Forschung [BMBF]) (Germany)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing planNot provided at time of registration

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Protocol article protocol 27/10/2014 Yes No
Basic results 21/03/2022 19/05/2022 No No

Editorial Notes

19/05/2022: EU Clinical Trials Register results added.
24/01/2019: The following changes have been made to the trial record:
1. The overall trial end date has been changed from 31/12/2015 to 05/07/2018
2. The EudraCT number was added
3. Ethics approval was changed from approval pending as of 11/05/2011 to approved as of 17/04/2013