Hydroxychloroquine as a Steroid-sparing Agent in Extrapulmonary Sarcoidosis: Multicenter, Prospective, Placebo-controlled, Randomized Trial

Status: Recruiting
Location: See all (21) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 4
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

⁃ at least 18 years of age

• pathologically proven sarcoidosis as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS)/World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) criteria

• non severe ocular sarcoidosis requiring systemic treatment

• non severe skin sarcoidosis requiring systemic treatment

• non severe osseous sarcoidosis requiring systemic treatment

• non severe sarcoidosis with joint involvement requiring systemic treatment

• non severe sarcoidosis-related hypercalcemia requiring systemic treatment

• non severe peripheral nervous system sarcoidosis requiring systemic treatment

• non severe sarcoidosis-related non-severe Ear, Nose and Throat (ENT) involvement requiring systemic treatment

• symptomatic hypercalciuria \>200 mg/24h (24 h urine) OR

∙ \- \> 20 mg/mmol creatinine on urine sample

‣ \- \> 180 mg/g creatinine on urine sample

• signed informed consent

• affiliated to National French social security system

Locations
Other Locations
France
Service de Médecine Interne Infectiologie Aïgue Polyvalente- Hôpital Henri Duffaud
RECRUITING
Avignon
Service de Pneumologie - Hôpital Avicenne
NOT_YET_RECRUITING
Bobigny
Service de medecine interne - Hôpital Henri Mondor
NOT_YET_RECRUITING
Créteil
Service de Médecine Interne et Immunologie Clinique - CHU Dijon Bourgogne
NOT_YET_RECRUITING
Dijon
Service de medecine interne - Hôpital Claude Huriez
NOT_YET_RECRUITING
Lille
Service de medecine interne - Hôpital Duputryen
NOT_YET_RECRUITING
Limoges
Service de médecine interne - Centre Hospitalier Saint Joseph Saint Luc
NOT_YET_RECRUITING
Lyon
Service de médecine interne - Hôpital de la Croix Rousse
RECRUITING
Lyon
Service de médecine interne - Hôpital Edouard Herriot
NOT_YET_RECRUITING
Lyon
Service de médecine interne - Hôpital Lyon Sud
NOT_YET_RECRUITING
Lyon
Service de medecine interne - Hôpital Saint Eloi
NOT_YET_RECRUITING
Montpellier
Service de medecine interne - Hôpital Hôtel Dieu
NOT_YET_RECRUITING
Nantes
Hôpital Cochin - Médecine interne
NOT_YET_RECRUITING
Paris
Hôpitaux Saint Joseph et Marie LANNELONGUE
NOT_YET_RECRUITING
Paris
Service de médecine interne - Hôpital Lariboisière
NOT_YET_RECRUITING
Paris
Service de medecine interne 2- Hôpital de la Pitié-Salpétrière
NOT_YET_RECRUITING
Paris
Service de Médecine Interne et maladies infectieuses - Hôpital Haut Lévêque
NOT_YET_RECRUITING
Pessac
Service de Médecine Interne et Immunologie Clinique - Hôpital Sud
RECRUITING
Rennes
Service de medecine interne - Hôpital Nord
NOT_YET_RECRUITING
Saint-etienne
Service de médecine interne - Clinique Saint exupéry
RECRUITING
Toulouse
CHU Tours - Médecine interne
NOT_YET_RECRUITING
Tours
Contact Information
Primary
Thomas El Jammal, Dr
thomas.el-jammal@chu-lyon.fr
04.26.73.26.29
Backup
Camille BOUCHENY
camille.boucheny@chu-lyon.fr
04 26 73 27 39
Time Frame
Start Date: 2024-07-30
Estimated Completion Date: 2029-07-01
Participants
Target number of participants: 140
Treatments
Experimental: 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_comparator: Placebo arm
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)
Sponsors
Leads: Hospices Civils de Lyon

This content was sourced from clinicaltrials.gov