Sarcoidosis, PulmonaryPhase 4CAESARNCT05841758
Hydroxychloroquine as a Steroid-sparing Agent in Extrapulmonary Sarcoidosis
A Phase 4 study testing Hydroxychloroquine in people with Sarcoidosis, Pulmonary, run by Hospices Civils de Lyon at 21 sites in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sarcoidosis, Pulmonary
- What is being tested?
- Hydroxychloroquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 21 sitesFrance
- Study dates
- 30 Jul 2024to 1 Jul 2029
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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)
Trial locations and contacts
21 sites in 1 country. Contact the study team or a site near you to ask about taking part.
21 sites in 1 country
France21 sites, 21 recruiting
- Recruiting
Service de Médecine Interne Infectiologie Aïgue Polyvalente- Hôpital Henri Duffaud
Avignon, 84 000
Philip Bielfed, Dr, 04 32 75 30 01, BIELEFELD.Philip@ch-avignon.fr
Philip Bielfed, Dr
- Not yet recruiting
Service de Pneumologie - Hôpital Avicenne
Bobigny, 93000
Hilario Nunes, Dr, 01 48 95 51 25 ext. 33, hilario.nunes@aphp.fr
Hilario Nunes, Dr
- Not yet recruiting
Service de medecine interne - Hôpital Henri Mondor
Créteil, 94000
Matthieu Mahévas, Dr, 01 49 81 20 76 ext. 33, matthieu.mahevas@aphp.fr
Matthieu Mahévas, Dr
- Not yet recruiting
Service de Médecine Interne et Immunologie Clinique - CHU Dijon Bourgogne
Dijon, 21 079
Bernard Bonnotte, Dr, 03 80 29 34 32, bernard.bonnotte@chu-dijon.fr
Bernard Bonnotte, Dr
- Not yet recruiting
Service de medecine interne - Hôpital Claude Huriez
Lille, 59 000
Emmanuel LEDOULT, Dr, 03 20 44 50 48, emmanuel.ledoult2@chu-lille.fr
Emmanuel LEDOULT
- Not yet recruiting
Service de medecine interne - Hôpital Duputryen
Limoges, 87 042
Kim Ly, Dr, 05 55 05 69 90, kim.ly@chu-limoges.fr
Kim Ly, Dr
- Recruiting
Service de médecine interne - Hôpital de la Croix Rousse
Lyon, 69004
Thomas El JAMMAL, Dr, 04.26.73.26.36, thomas.el-jammal@chu-lyon.fr
Thomas EL JAMMAL, MD
- Not yet recruiting
Service de médecine interne - Hôpital Edouard Herriot
Lyon, 69004
Barba Thomas, Dr, 04 72 11 77 91 ext. 33, Thomas.barba@chu-lyon.fr
Thomas Barba, Dr
- Recruiting
Service de médecine interne - Hôpital Lyon Sud
Lyon, 69004
Reynaud Quitterie, Dr, 04 78 86 13 54, Reynaud.quitterie@chu-lyon.fr
Reynaud Quitterie, Pr
- Not yet recruiting
Service de médecine interne - Centre Hospitalier Saint Joseph Saint Luc
Lyon, 69007
Laurent Perard, Dr, 04 78 61 83 08 ext. 33, lperard@ch-stjoseph-stluc-lyon.fr
Laurent Perard, Dr
- Not yet recruiting
Service de medecine interne - Hôpital Saint Eloi
Montpellier, 34 295
Sophie Rivière, Dr, 04 67 33 05 94, s-riviere@chu-montpellier.fr
Sophie Rivière, Dr
- Not yet recruiting
Service de medecine interne - Hôpital Hôtel Dieu
Nantes, 44000
Antoine Néel, Dr, 02 40 08 33 55, mohamed.hamidou@chu-nantes.fr
Antoine Néel, Dr
- Not yet recruiting
Service de médecine interne - Hôpital Lariboisière
Paris, 75010
Damien Sène, Dr, 01 49 95 63 21, damien.sene@aphp.fr
Damien Sène, Dr
- Not yet recruiting
Service de medecine interne 2- Hôpital de la Pitié-Salpétrière
Paris, 75013
Fleur Cohen, Dr, 01 42 17 81 66, Fleur.cohen@aphp.fr
Fleur Cohen, Dr
- Not yet recruiting
Hôpital Cochin - Médecine interne
Paris
Alexis REGENT, MD, 158411455 ext. +33, alexis.regent@aphp.fr
Alexis REGENT, MD
- Not yet recruiting
Hôpitaux Saint Joseph et Marie LANNELONGUE
Paris
Jean-Marc NACCACHE, MD, 144127582 ext. +33, jmnaccache@ghpsj.fr
Jean-Marc NACCACHE, MD
- Recruiting
Service de Médecine Interne et maladies infectieuses - Hôpital Haut Lévêque
Pessac, 33 604
Jean-François Viallard, 05 57 65 64 83, jean-francois.viallard@chu-bordeaux.fr
Jean-François Viallard, MD
- Recruiting
Service de Médecine Interne et Immunologie Clinique - Hôpital Sud
Rennes, 35 2000
Nicolas Belhomme, Dr, 02 99 26 71 28, nicolas.belhomme@chu-rennes.fr
Nicolas Belhomme, dr
- Not yet recruiting
Service de medecine interne - Hôpital Nord
Saint-Etienne, 42 055
Killian Martin, Dr, 04 77 82 83 42, pascal.cathebras@chu-st-etienne.fr
Killian Martin, Dr
- Recruiting
Service de médecine interne - Clinique Saint exupéry
Toulouse, 31077
Martin Michaud, Dr, 05 61 17 33 33 ext. 33, Martin.MICHAUD@clinique-saint-exupery.com
Martin Michaud, Dr
- Not yet recruiting
CHU Tours - Médecine interne
Tours
Stéphanie JOBARD, MD, 218370882 ext. +33, s.jobard@chu-tours.fr
Stéphanie JOBARD, MD
About this study
Official title: Hydroxychloroquine as a Steroid-sparing Agent in Extrapulmonary Sarcoidosis: Multicenter, Prospective, Placebo-controlled, Randomized Trial
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.
- Conditions
- Sarcoidosis, Pulmonary
- Being tested
- Hydroxychloroquine, Placebo
- Keywords
- Sarcoidosis, Hydroxychloroquine, steroid-sparing agent, Extra pulmonary sarcoidosis
- Medical subject headings
- Sarcoidosis, Pulmonary, Sarcoidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydroxychloroquine (200-400 mg /day during a 12 months double blind placebo-controlled period)
PlaceboDrug
Placebo during a 12 months double blind placebo-controlled period
| Study group | Role | What they receive |
|---|---|---|
| Hydroxychloroquine | Experimental | 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) Receives: Drug: Hydroxychloroquine |
| Placebo arm | Placebo comparator | 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) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the steroid-sparing effect of hydroxychloroquine as an add-on therapy in patients with non severe extra-pulmonary sarcoidosis requiring a systemic treatment.
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.
Measured: at Year 1
Secondary outcomes (14)
Organ-specific response assessed by the extra-pulmonary Physician Organ Severity Tool (ePOST)
score comprised between 0 and 6
Measured: at Month 0, Month 1, Month 3, Month 6, Month 12, Month 18 and Month 24.
rate of complete, partial, stable or progression of the disease
Global clinical response will be assessed by the physician as complete, partial, stable, or progression
Measured: at Month 0, Month 1, Month 3, Month 6, Month 12, Month 18 and Month 24.
Assess the total dose of local steroid treatments
Total dose in Gramme of local steroid treatments
Measured: at Month 0, Month 1, Month 3, Month 6, Month 12, Month 18 and Month 24.
Assess the efficacy of HCQ in maintaining the relapse-free survival over a prolonged period
Relapse rate
Measured: at Month 0, Month 1, Month 3, Month 6, Month 12, Month 18 and Month 24.
Assess and compare the eventual reduction of steroid-related toxicity (side effects)
Frequencies of steroid-associated side-effects monitored clinically and biologically
Measured: at Month 0, Month 1, Month 3, Month 6, Month 12, Month 18 and Month 24.
Assess HCQ safety
HCQ safety will be assessed through initial and annual electroretinogram
Measured: at Month 3, Month 6 and Month 12
Assess HCQ safety
HCQ safety will be assessed through initial and annual autofluorescence
Measured: at Month 3, Month 6 and Month 12
Assess HCQ safety
HCQ safety will be assessed through initial and annual electroretinogram or autofluorescence or Optical Coherence Tomography (OCT), yearly eye evaluation and monitoring of eventual Adverse Event (AE)s. An AE will be considered as serious if it leads to HCQ cessation, hospitalization, or death.
Measured: at Month 3, Month 6 and Month 12
Assess HCQ safety
HCQ safety will be assessed through yearly eye evaluation with monitoring of eventual Adverse Event (AE)s. An AE will be considered as serious if it leads to HCQ cessation, hospitalization, or death.
Measured: at Month 3, Month 6 and Month 12
Assess HCQ safety
HCQ safety will be assessed through Optical Coherence Tomography (OCT)
Measured: at Month 3, Month 6 and Month 12
Assess patients' adherence
Patient's adherence will be controlled by patient notebooks
Measured: at Month 3, Month 6 and Month 12
Assess patients' adherence
Patient's adherence will be controlled by pharmacy count of returned tablets
Measured: at Month 3, Month 6 and Month 12
Assess patients' adherence
Patient's adherence will be controlled by serial dosages of blood HCQ levels
Measured: at Month 3, Month 6 and Month 12
Assess quality of life by the Study Short Form 36 questionnaire (SF-36 questionnaire).
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.
Measured: at Month 0, Month 1, Month 3, Month 6, Month 12, Month 18 and Month 24.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2023
- Study start30 Jul 2024
- Primary completion1 Jul 2029 (estimated)
- Study completion1 Jul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sarcoidosis, PulmonaryStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05841758
- Sponsor's protocol ID
- 69HCL21_1054
- Other IDs
- 2022-502155-65-00
- Acronym
- CAESAR
- Status last verified
- Sep 2026
- First submitted
- 17 Mar 2023
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No