Hydroxychloroquine as a Steroid-sparing Agent in Extrapulmonary Sarcoidosis
- Registration Number
- NCT05841758
- Lead Sponsor
- Hospices Civils de Lyon
- Brief Summary
Sarcoidosis is a systemic granulomatous disease of unknown aetiology, mainly affecting the lungs and lymphatics. It affects people worldwide (incidence, 4.7-64/100000; prevalence, 1-36/100000/year). Although it is most often a benign acute or subacute condition, sarcoidosis may progress to a disabling chronic disease in 25% of the cases, with severe complications in about 5%, such as lung fibrosis, cardiac or neurosarcoidosis, defacing lupus pernio or blindness due to uveitis.
When indicated, corticosteroids (CS) are the mainstay of treatment. Due to the kinetics of granuloma resolution, the usual and quite 'dogmatic' duration of treatment is said to be one year, following four classical steps. The long-term use of CS is hindered by cumulative toxicity and efforts have to be made to taper them, as quickly as possible, to the lowest effective dose. A recent report mentioned 39% of the CS-treated patients requiring a steroid-sparing agent. Chloroquine (CQ) and hydroxychloroquine (HCQ) are anti-malarial drugs that have been used since the 1960's as steroidsparing agents on the basis of a landmark study by Siltzbach reporting their efficacy in 43 patients with skin and intrathoracic sarcoidosis. Subsequently, two small randomized controlled trials have shown significant and prolonged improvement on pulmonary symptoms. Only small case series/reports have shown CQ/HCQ efficacy on extra-pulmonary sarcoidosis with response rates ranging from 67 to 100%. Nevertheless, CQ/HCQ are daily used for skin, bone, and joint sarcoidosis, as well as hypercalcemia. Nowadays, HCQ is preferred over CQ because of a lower incidence of gastrointestinal and ocular adverse reactions, which can be minimized by close attention to the dosage and regular retinal examination. Its profile of safety is well-known since it has long been employed to treat systemic lupus erythematous or rheumatoid arthritis. Its action is thought to rely on its ability to accumulate in lysosomes of phagocytic cells, to affect antigen presentation and reduce pro-inflammatory cytokines. The investigator hypothesize that HCQ may be an efficacious add-on therapy for extra-pulmonary sarcoidosis leading to a significant steroid-sparing effect.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 140
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Hydroxychloroquine Hydroxychloroquine prednisone (scheduled protocol) + hydroxychloroquine (200-400 mg /day during a 12 months double blind placebo-controlled period, then according to the treating the physician for an additional open period of 12 months) Placebo arm Placebo prednisone (scheduled protocol) + placebo (1-2 tablets/day during a 12 months double blind placebocontrolled period, then the treatment is left to the physician's discretion until M24)
- Primary Outcome Measures
Name Time Method Evaluate the steroid-sparing effect of hydroxychloroquine as an add-on therapy in patients with non severe extra-pulmonary sarcoidosis requiring a systemic treatment. at Year 1 The primary endpoint is the percentage of patients in remission and off prednisone at month 9, without relapse until month 12. The primary endpoint will thus be assessed at M12.
Remission is defined by either complete or partial response. Complete response is defined as the absence of clinical or paraclinical sign of disease activity. Partial response is defined as the persistence of clinical or paraclinical sign of disease activity, which do not require substantial treatment modification (high dose CS, immunosuppressant or anti-Tumor Necrosis Factor (TNF) drugs). Relapse is defined as the persistence, or recurrence of existing manifestations and/or the occurrence of new sarcoidosis manifestations requiring substantial treatment modification.
- Secondary Outcome Measures
Name Time Method Assess the total dose of local steroid treatments at Month 0, Month 1, Month 3, Month 6, Month 12, Month 18 and Month 24. Total dose in Gramme of local steroid treatments
Assess the efficacy of HCQ in maintaining the relapse-free survival over a prolonged period at Month 0, Month 1, Month 3, Month 6, Month 12, Month 18 and Month 24. Relapse rate
Organ-specific response assessed by the extra-pulmonary Physician Organ Severity Tool (ePOST) at Month 0, Month 1, Month 3, Month 6, Month 12, Month 18 and Month 24. score comprised between 0 and 6
Assess patients' adherence at Month 3, Month 6 and Month 12 Patient's adherence will be controlled by serial dosages of blood HCQ levels
Assess quality of life by the Study Short Form 36 questionnaire (SF-36 questionnaire). at Month 0, Month 1, Month 3, Month 6, Month 12, Month 18 and Month 24. 11 questions are asked, the minimum score is 36 and the maximum score is 149. Statistical analysis of the SF-36 questionnaire will be performed by a statician, analysis is more complex than only higher score means better health.
rate of complete, partial, stable or progression of the disease at Month 0, Month 1, Month 3, Month 6, Month 12, Month 18 and Month 24. Global clinical response will be assessed by the physician as complete, partial, stable, or progression
Assess and compare the eventual reduction of steroid-related toxicity (side effects) at Month 0, Month 1, Month 3, Month 6, Month 12, Month 18 and Month 24. Frequencies of steroid-associated side-effects monitored clinically and biologically
Assess HCQ safety at Month 3, Month 6 and Month 12 HCQ safety will be assessed through Optical Coherence Tomography (OCT)
Trial Locations
- Locations (21)
Service de Médecine Interne Infectiologie Aïgue Polyvalente- Hôpital Henri Duffaud
🇫🇷Avignon, France
Service de Pneumologie - Hôpital Avicenne
🇫🇷Bobigny, France
Service de medecine interne - Hôpital Henri Mondor
🇫🇷Créteil, France
Service de Médecine Interne et Immunologie Clinique - CHU Dijon Bourgogne
🇫🇷Dijon, France
Service de medecine interne - Hôpital Claude Huriez
🇫🇷Lille, France
Service de medecine interne - Hôpital Duputryen
🇫🇷Limoges, France
Service de médecine interne - Hôpital de la Croix Rousse
🇫🇷Lyon, France
Service de médecine interne - Hôpital Edouard Herriot
🇫🇷Lyon, France
Service de médecine interne - Hôpital Lyon Sud
🇫🇷Lyon, France
Service de médecine interne - Centre Hospitalier Saint Joseph Saint Luc
🇫🇷Lyon, France
Scroll for more (11 remaining)Service de Médecine Interne Infectiologie Aïgue Polyvalente- Hôpital Henri Duffaud🇫🇷Avignon, FrancePhilip Bielfed, DrPrincipal Investigator