Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
2011 05 30-1
Study information
Scientific title
Prospective, randomised, double-blind, placebo-controlled clinical trial with hydroxychloroquine (HCQ) in patients with inflammatory osteoarthritis (OA) of the hands
Acronym
OA Treat
Study hypothesis
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
Approval pending as of 11/05/2011
Study design
Interventional randomised placebo-controlled double-blind multicentre study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
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
Other
Phase
Not Applicable
Drug names
Primary outcome measure
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
Secondary outcome measures
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)
Overall trial start date
04/12/2011
Overall trial end date
31/12/2015
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
510
Participant 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
Recruitment start date
04/12/2011
Recruitment end date
31/12/2015
Locations
Countries of recruitment
Germany
Trial participating centre
Charité - University of Medicine, Berlin
Berlin
10117
Germany
Sponsor information
Organisation
Charité - University of Medicine, Berlin (Germany)
Sponsor details
c/o Prof. Gerd-R. Burmester
Department of Rheumatology and Clinical Immunology
Charitéplatz 1
Berlin
10117
Germany
+49 (0)30 450 513 061
gerd.burmester@charite.de
Sponsor type
University/education
Website
Funders
Funder type
Government
Funder name
German Federal Ministry of Education and Research (Bundesministerium Fur Bildung und Forschung [BMBF]) (Germany)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2014 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/25348033
Publication citations
-
Protocol
Detert J, Klaus P, Listing J, Höhne-Zimmer V, Braun T, Wassenberg S, Rau R, Buttgereit F, Burmester GR, Hydroxychloroquine in patients with inflammatory and erosive osteoarthritis of the hands (OA TREAT): study protocol for a randomized controlled trial., Trials, 2014, 15, 1, 412, doi: 10.1186/1745-6215-15-412.