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

ISRCTN	ISRCTN46445413
DOI	https://doi.org/10.1186/ISRCTN46445413
Clinical Trials Information System (CTIS)	2011-001689-16
Protocol serial number	2011 05 30-1
Sponsor	Charité - University of Medicine, Berlin (Germany)
Funder	German Federal Ministry of Education and Research (Bundesministerium Fur Bildung und Forschung [BMBF]) (Germany)

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

Primary study design	Interventional
Study design	Interventional randomised placebo-controlled double-blind multicentre study
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Prospective, randomised, double-blind, placebo-controlled clinical trial with hydroxychloroquine (HCQ) in patients with inflammatory osteoarthritis (OA) of the hands
Study acronym	OA Treat
Study objectives	Osteoarthritis (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) studied	Refractory inflammatory hand osteoarthritis
Intervention	Arm 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 type	Drug
Phase	Phase III
Drug / device / biological / vaccine name(s)	Hydroxychloroquine
Primary outcome measure(s)	1. 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
Key secondary outcome measure(s)	1. Efficacy of HCQ with respect to AUSCAN at week 26 to patients global assessment of disease activity, patients assessment of stiffness, and physicians 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)
Completion date	05/07/2018

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	510
Key inclusion criteria	1. 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 criteria	1. 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 enrolment	04/12/2011
Date of final enrolment	31/12/2015

Locations

Countries of recruitment

Germany

Study participating centre

Charité - University of Medicine, Berlin

Berlin
10117
Germany

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan	Not 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
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

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