Informations générales (source: ClinicalTrials.gov)
Hydroxychloroquine as a Steroid-sparing Agent in Extrapulmonary Sarcoidosis: Multicenter, Prospective, Placebo-controlled, Randomized Trial (CAESAR)
Interventional
Phase 4
Hospices Civils de Lyon (Voir sur ClinicalTrials)
juillet 2024
juillet 2029
02 juillet 2025
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.
Etablissements
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| AP-HP - Hôpital Avicenne | Hilario Nunes, Dr | Contact (sur clinicalTrials) | |||
| AP-HP - Hôpital Cochin | Alexis REGENT, MD | Contact (sur clinicalTrials) | |||
| AP-HP - Hôpital Henri Mondor-Albert Chenevier | Matthieu Mahévas, Dr | Contact (sur clinicalTrials) | |||
| GH PARIS SITE SAINT JOSEPH | Jean-Marc NACCACHE, MD | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| CHU Tours - Médecine interne - Tours - France | Stéphanie JOBARD, MD | Contact (sur clinicalTrials) | |||
| Service de médecine interne - Centre Hospitalier Saint Joseph Saint Luc - 69007 - Lyon - France | Laurent Perard, Dr | Contact (sur clinicalTrials) | |||
| Service de médecine interne - Clinique Saint exupéry - 31077 - Toulouse - France | Martin Michaud, Dr | Contact (sur clinicalTrials) | |||
| Service de medecine interne - Hôpital Claude Huriez - 59 000 - Lille - France | Emmanuel LEDOULT, Dr | Contact (sur clinicalTrials) | |||
| Service de médecine interne - Hôpital de la Croix Rousse - 69004 - Lyon - France | Thomas El JAMMAL, Dr | Contact (sur clinicalTrials) | |||
| Service de medecine interne - Hôpital Duputryen - 87 042 - Limoges - France | Kim Ly, Dr | Contact (sur clinicalTrials) | |||
| Service de médecine interne - Hôpital Edouard Herriot - 69004 - Lyon - France | Barba Thomas, Dr | Contact (sur clinicalTrials) | |||
| Service de medecine interne - Hôpital Hôtel Dieu - 44000 - Nantes - France | Antoine Néel, Dr | Contact (sur clinicalTrials) | |||
| Service de médecine interne - Hôpital Lariboisière - 75010 - Paris - France | Damien Sène, Dr | Contact (sur clinicalTrials) | |||
| Service de médecine interne - Hôpital Lyon Sud - 69004 - Lyon - France | Reynaud Quitterie, Dr | Contact (sur clinicalTrials) | |||
| Service de medecine interne - Hôpital Nord - 42 055 - Saint-Étienne - France | Killian Martin, Dr | Contact (sur clinicalTrials) | |||
| Service de medecine interne - Hôpital Saint Eloi - 34 295 - Montpellier - France | Sophie Rivière, Dr | Contact (sur clinicalTrials) | |||
| Service de medecine interne 2- Hôpital de la Pitié-Salpétrière - 75013 - Paris - France | Fleur Cohen, Dr | Contact (sur clinicalTrials) | |||
| Service de Médecine Interne et Immunologie Clinique - CHU Dijon Bourgogne - 21 079 - Dijon - France | Bernard Bonnotte, Dr | Contact (sur clinicalTrials) | |||
| Service de Médecine Interne et Immunologie Clinique - Hôpital Sud - 35 2000 - Rennes - France | Nicolas Belhomme, Dr | Contact (sur clinicalTrials) | |||
| Service de Médecine Interne et maladies infectieuses - Hôpital Haut Lévêque - 33 604 - Pessac - France | Jean-François Viallard | Contact (sur clinicalTrials) | |||
| Service de Médecine Interne Infectiologie Aïgue Polyvalente- Hôpital Henri Duffaud - 84 000 - Avignon - France | Philip Bielfed, Dr | Contact (sur clinicalTrials) | |||
Critères
Tous
- Inclusion Criteria :
- 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
- Exclusion Criteria :
- severe sarcoidosis involvement requiring another immunosuppressant or anti-TNF
antibody or methylprednisolone i.v. pulses
- previous (<3 months before screening) or concurrent treatment with
immunosuppressants
- previous treatment with corticoid (patient weaned for 3 months before
inclusion)
- previous treatment with antimalarial drugs (HCQ/CQ) (patient must have been off
plaquenil for at least 12 months)
- treatment with citalopram, escitalopram, hydroxyzin, domperidone and
piperaquine
- known hypersensitivity or intolerance to HCQ/CQ or 4-aminoquinoline derivatives
and prednisone
- heart rhythm disorders on EKG (QT prolongation) (except atrial fibrillations)
- severe ophthalmological impairment or ophthalmological impairment that does not
allow ophthalmic monitoring; previous history of maculopathy or retinopathy
- end-stage lung, liver, cardiac, or renal disease
- sarcoidosis with central nervous system involvement
- cardiac sarcoidosis
- clinical evidence of active infection (including infection with herpes virus
and varicella-zoster virus) or severe/unstabilized comorbidity (e.g. moderate
to severe heart failure) or unstabilized psychosis
- chronic viral (HIV or HBV) infection
- untreated latent/active tuberculosis
- pregnancy or lactation (βHCG will be test by blood analysis at inclusion)
- concurrent vaccination with live vaccines during therapy
- inability to understand information about the protocol and to sign informed
consent or not suitable candidate to comply with the requirements of this study
- patient participating in other interventional research
- persons under court protection
- Use of effective contraception for the duration of the study . (Contraception
is considered effective when it consists of one of the following: use of a male
condom during all sexual activity and/or efficient oral hormonal contraception
(better considered combined contraception) and/or an intrauterine device (IUD)
and/or hormone-releasing intrauterine system (IUS) and/or history of bilateral
tubal ligation and/or history of vasectomy, provided the male partner is the
trial participant's only sexual partner and/or sexual abstinence)
- 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
- Exclusion Criteria :
- severe sarcoidosis involvement requiring another immunosuppressant or anti-TNF
antibody or methylprednisolone i.v. pulses
- previous (<3 months before screening) or concurrent treatment with
immunosuppressants
- previous treatment with corticoid (patient weaned for 3 months before
inclusion)
- previous treatment with antimalarial drugs (HCQ/CQ) (patient must have been off
plaquenil for at least 12 months)
- treatment with citalopram, escitalopram, hydroxyzin, domperidone and
piperaquine
- known hypersensitivity or intolerance to HCQ/CQ or 4-aminoquinoline derivatives
and prednisone
- heart rhythm disorders on EKG (QT prolongation) (except atrial fibrillations)
- severe ophthalmological impairment or ophthalmological impairment that does not
allow ophthalmic monitoring; previous history of maculopathy or retinopathy
- end-stage lung, liver, cardiac, or renal disease
- sarcoidosis with central nervous system involvement
- cardiac sarcoidosis
- clinical evidence of active infection (including infection with herpes virus
and varicella-zoster virus) or severe/unstabilized comorbidity (e.g. moderate
to severe heart failure) or unstabilized psychosis
- chronic viral (HIV or HBV) infection
- untreated latent/active tuberculosis
- pregnancy or lactation (βHCG will be test by blood analysis at inclusion)
- concurrent vaccination with live vaccines during therapy
- inability to understand information about the protocol and to sign informed
consent or not suitable candidate to comply with the requirements of this study
- patient participating in other interventional research
- persons under court protection
- Use of effective contraception for the duration of the study . (Contraception
is considered effective when it consists of one of the following: use of a male
condom during all sexual activity and/or efficient oral hormonal contraception
(better considered combined contraception) and/or an intrauterine device (IUD)
and/or hormone-releasing intrauterine system (IUS) and/or history of bilateral
tubal ligation and/or history of vasectomy, provided the male partner is the
trial participant's only sexual partner and/or sexual abstinence)