Trial document





This trial has been registered retrospectively.
drksid header

  DRKS00000796

Trial Description

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Title

Prospective randomized, double-blind, and placebo-controlled clinical trial with
hydroxychloroquine (HCQ) in patients with inflammatory osteoarthritis (OA) of
the hands

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

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.

4. Amendment applicated 08.12.2015
Leading Ethical Committe Approval 13.01.2016

Changes in target sample size.
Amended exclusion criteria 16 - malignancy.

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Brief Summary in Scientific Language

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 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) signaling, 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 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.

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Organizational Data

  •   DRKS00000796
  •   2015/03/23
  •   [---]*
  •   yes
  •   Approved
  •   13/0029 - EK 13, Ethik-Kommission des Landes Berlin
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Secondary IDs

  •   U1111-1121-1623 
  •   2011-001689-16 
  •   4038845 
  •   01KG1106  (BMBF-Förderkennzeichen)
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Health Condition or Problem studied

  •   M15.4 -  Erosive (osteo)arthrosis
  •   M15.9 -  Polyarthrosis, unspecified
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Interventions/Observational Groups

  •   Capsules body weight adapted to pharmaceutical package (30 - 49 kg one capsule with 200 mg HCQ as daily single dose; 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; > 65 kg two capsules with 200 mg HCQ as single dose)
  •   One capsule with oral placebo application
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, investigator/therapist, caregiver, assessor, data analyst
  •   Placebo
  •   Treatment
  •   Parallel
  •   II-III
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Primary Outcome

Clinical endpoint: Australian-Canadian OA Index
(AUSCAN, German version) for pain, and hand disability as co-primary clinical outcome at week 52.

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Secondary Outcome

1) 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)Radiographic progression assessed by the
Kallman Score at week 52.
3) 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.
4) 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.
5) To compare cumulative dosage of consumption per week of standard therapy
(NSAIDs, Coxibs)

6) Assessment of safety: Safety and tolerability of HCQ with reports on AE and SAE.
7) The eye examination will be performed by an ophthalmologist (baseline and every 6 months).

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

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Recruitment

  •   Actual
  •   2013/11/21
  •   202
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   40   Years
  •   80   Years
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Additional Inclusion Criteria

1) Men and women from 40 to 80 years.
2) Presence of clinical inflammatory hand OA according to ACR criteria.
3) Conforming to the ACR criteria for hand OA supported by X-ray of both hands, dating less than 6 months ago, X-ray of the hands
showing radiological signs of digital erosive OA in one or more joints. This criterion is checked by a central assessment.
4) Symptoms of digital inflammatory OA (pressure pain of the joints and/or florid joint swelling and/or redness and/or warmth) with more than 3 finger joints for more than 3 months despite taking analgesics and NSAIDs. An existing medication with NSAIDs/coxibs
should be continued according to the individual need two weeks prior to study entry.
5) Pain ≥ 4 as evaluated by the AUSCAN-NRS (0 – 10),
6) Function as co-primary clinical outcome with ≥ 26 using the AUSCAN.
7) The ability to understand the trial information for patients [AMG
§40 (1) and 3b],
8) The ability to sign the informed consent form including written the data protection form [according AMG § 40(1) and 3b]

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Exclusion Criteria

1) Patients who are currently treated with HCQ or have received HCQ in the past due to OA of the hands already.
2) Patients who have not been tolerated HCQ (e. g. skin disease or malaria prophylaxis) or patients who HCQ was discontinued due to
an eye disease (e. g. by an ophthalmologist).
3) Existence of painful syndrome of upper limbs likely to interfere with the monitoring of pain.
4) Patients suffering or having suffered from secondary OA after one of the following diseases (e. g. infectious arthritis, acromegaly,
ochronosis, hemochromatosis, Gout, etc.) or inflammatory joint diseases.
5) Any unstable medical condition which would expose the patient to an unacceptable risk.
6) Planned Surgery.
7) Local injection of finger- or hand joints with glucocorticoids or other medications within the previous three months.
8) Current intake of oral, intra–articular (i.a.) or systemic glucocorticoids (i.v., i.m.).
9) Presence of retinopathy.
10) Known hypersensitivity to HCQ or to one of the drug in this study protocol and treatment with digoxine.
11) Other serious clinical situations that expose the patient at risk of the opinion of the local investigator.
12) Current participation in another clinical trial or taking an experimental treatment.
13) Patients who are underage or are incapable to understand the aim,
importance and consequences of the study and to give legal informed consent [according to AMG § 40(4) and § 42(2) and (3)].
14) Prisoners, and persons Patients who are institutionalized due to regulatory or judicial order [according to AMG § 40(1), no. 4]
15) Pregnant and breastfeeding women.
16) Have had lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of
the skin that have been resected with no evidence of recurrence for at least 5 years prior to screening.

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Addresses

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    • Charité - Universitätsmedizin Berlin Dep. Rheumatology and Clinical Immunology, CC12
    • Mr.  Prof.  Gerd-R.  Burmester 
    • Charitéplatz 1
    • 10117  Berlin
    • Germany
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    • Charité - Universitätsmedizin Berlin Dep. Rheumatology and Clinical Immunology, CC12
    • Ms.  Dr.  Jacqueline  Detert 
    • Charitéplatz 1
    • 10117  Berlin
    • Germany
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    • Charité - Universitätsmedizin Berlin Dep. Rheumatology and Clinical Immunology
    • Ms.  Dr.   Jacqueline   Detert 
    • Charitéplatz 1
    • 10117  Berlin
    • Germany
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    • Charité - Universitätsmedizin Berlin Dep. Rheumatology and Clinical Immunology, CC12
    • Ms.  Studienkoordinatorin  Tanja  Braun 
    • Charitéplatz 1
    • 10117  Berlin
    • Germany
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Sources of Monetary or Material Support

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    • Bundesministerium für Bildung und Forschung BMBF Lebenswissenschaften
    • Heinrich-Konen-Str. 1
    • 53227   Bonn
    • Germany
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Status

  •   Recruiting complete, follow-up complete
  •   2018/07/05
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Trial Publications, Results and other Documents

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