QUIDOSE: Randomized Controlled Trial of Hydroxychloroquine Combined With Low-dose Corticosteroid in Pulmonary Sarcoidosis

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05247554

Collaborator

(none)

200

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

"The reference treatment for pulmonary sarcoidosis is prolonged systemic corticosteroid therapy, which improves dyspnea, fatigue and respiratory function. However, corticosteroid therapy doesn't improve quality of life, possibly due to its adverse effects. Furthermore, in an international survey study, the first priority in treatment outcome for sarcoidosis patient was quality of life.

Hydroxychloroquine an antimalarial drug, has been shown to be effective in cutaneous and pulmonary forms of sarcoidosis but in studies with imperfect methodology. Our hypothesis is that hydroxychloroquine associated with low-dose corticosteroids improves lung function as much as conventional medium-dose corticosteroid therapy but with fewer side effects and a better quality of life in pulmonary sarcoidosis. "

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Sarcoidosis	Drug: Hydroxychloroquine + low-dose prednisone Drug: Prednisone	Phase 3

Detailed Description

"Sarcoidosis is a systemic granulomatosis of unknown etiology with almost systematic pulmonary involvement. The reference treatment for pulmonary sarcoidosis is prolonged systemic corticosteroid therapy, which improves dyspnea, fatigue and respiratory function. However, corticosteroid therapy doesn't improve quality of life, possibly due to its adverse effects, which are dose- and time-dependent, such as weight gain, diabetes, insomnia, hypertension. Furthermore, in an international survey study, the first priority in treatment outcome for sarcoidosis patient was quality of life. Recent optimizations have reduced the attack treatment duration from 3 to 1 month, but with a persistence of adverse effects appearing in the first months.

Hydroxychloroquine is an antimalarial drug, used for systemic lupus erythematosus with a very good benefit/risk ratio and low cost, but also for rheumatoid arthritis. Its anti-inflammatory effects involve inhibition of antigenic presentation, chemotaxis, phagocytosis, lymphocyte proliferation, cytokine production (e.g TNFα), or Toll-like receptors expression. These immunological mechanisms are also involved in the pathogenesis of sarcoidosis. In addition, Hydroxychloroquine decreases the risk of developing diabetes mellitus, dyslipidemia or thrombotic events. Hydroxychloroquine has been shown to be effective in cutaneous and pulmonary forms of sarcoidosis, and in hypercalcemia, but in studies with imperfect methodology. Baltzan et al. showed that a maintenance treatment of hydroxychloroquine versus placebo reduced the risk of relapse and lung function decline in pulmonary sarcoidosis. Our hypothesis is that hydroxychloroquine associated with low-dose corticosteroids improves lung function as much as conventional medium-dose corticosteroid therapy but with fewer side effects and a better quality of life in pulmonary sarcoidosis. The main objective is to demonstrate the non-inferiority of the combination of hydroxychloroquine and low-dose corticosteroids versus medium-dose corticosteroid therapy on the improvement of respiratory function at 6 months.

The secondary objectives are to (i) demonstrate the superiority of the combination of hydroxychloroquine and low-dose corticosteroids versus medium-dose corticosteroid therapy at 3, 6 months and 1 year on general quality of life, respiratory quality of life, fatigue, adverse drug event, treatment compliance and (ii) demonstrate the non-inferiority of the combination of hydroxychloroquine and low-dose corticosteroids versus medium-dose corticosteroid therapy at 3, 6 months and 1 year on : respiratory function using complementary tools, respiratory symptoms, and activity of thoracic and extra-thoracic sarcoidosis. "

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Randomized Controlled Trial Testing the Effect of Hydroxychloroquine Combined With Low-dose Corticosteroid Therapy in Pulmonary Sarcoidosis

Anticipated Study Start Date :

Mar 1, 2022

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hydroxychloroquine+low-dose prednisone Hydroxychloroquine, tablets, 400mg/day for 6 months combined with Prednisone, 20mg/day for 1 month, then 10mg/day for 20 weeks (ie up to M6). The cumulative doses of prednisone during the 6 months of the study will be 1820mg	Drug: Hydroxychloroquine + low-dose prednisone Hydroxychloroquine, tablets, 400mg/day for 6 months combined with Prednisone, 20mg/day for 1 month, then 10mg/day for 20 weeks (ie up to M6). The cumulative doses of prednisone during the 6 months of the study will be 1820mg Other Names: Experimental Arm
Active Comparator: Medium-dose prednisone "prednisone, tablets, 40mg/day for 4 weeks, then 30mg/day for 2 weeks, then 20mg/day for 2 weeks, then 15mg/day for 2 weeks, then 10mg/day for 14 weeks (i.e. up to M6). The cumulative doses of prednisone during the 6 months of the study will be 2870mg "	Drug: Prednisone "prednisone, tablets, 40mg/day for 4 weeks, then 30mg/day for 2 weeks, then 20mg/day for 2 weeks, then 15mg/day for 2 weeks, then 10mg/day for 14 weeks (i.e. up to 6 months ). The cumulative doses of prednisone during the 6 months of the study will be 2870mg " Other Names: Standard Arm

Arm

Intervention/Treatment

Experimental: Hydroxychloroquine+low-dose prednisone

Hydroxychloroquine, tablets, 400mg/day for 6 months combined with Prednisone, 20mg/day for 1 month, then 10mg/day for 20 weeks (ie up to M6). The cumulative doses of prednisone during the 6 months of the study will be 1820mg

Drug: Hydroxychloroquine + low-dose prednisone

Other Names:

Experimental Arm

Active Comparator: Medium-dose prednisone

"prednisone, tablets, 40mg/day for 4 weeks, then 30mg/day for 2 weeks, then 20mg/day for 2 weeks, then 15mg/day for 2 weeks, then 10mg/day for 14 weeks (i.e. up to M6). The cumulative doses of prednisone during the 6 months of the study will be 2870mg "

Drug: Prednisone

"prednisone, tablets, 40mg/day for 4 weeks, then 30mg/day for 2 weeks, then 20mg/day for 2 weeks, then 15mg/day for 2 weeks, then 10mg/day for 14 weeks (i.e. up to 6 months ). The cumulative doses of prednisone during the 6 months of the study will be 2870mg "

Other Names:

Standard Arm

Outcome Measures

Primary Outcome Measures

Difference in percentage of the predicted forced vital capacity (FVC) between inclusion and 6 months [6 months]
"Difference in percentage of the predicted forced vital capacity (FVC) between inclusion and 6 months "

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age between 18-80 years old
Pulmonary sarcoidosis meeting the diagnostic criteria form ATS 2020 AJRCCM diagnostic criteria.
Patient with radiographic stage II (mediastinal-hilar bilateral lymphadenopathy and parenchymal involvement) or III (involvement pulmonary parenchymatous) and FVC<80% and respiratory symptom(s) among the following: cough, dyspnea, chest pain).
Effective contraception for women of childbearing ages
Informed consent signed.
Affiliation to the social security system

Exclusion Criteria:

Severe impairment requiring an immediate and urgent result and/or high doses of corticosteroids (neurological, cardiac, ophthalmic (severe uveitis with ocular sequala), laryngeal, nasosinusal, renal, severe hypercalcemia)
Cardiomyopathy with heart failure
Presence of other conditions that may influence respiratory function: COPD, Asthma, Obesity (BMI>30) pulmonary fibrosis disease, pulmonary neoplasia;
Contraindication to hydroxychloroquinehypersensitivity to active substances or to excipients, retinopathy or severe cataract, or unilateral blindness, QTc prolongation, exposure to known treatments to prolong QT)
Tamoxifen use
Renal insufficiency with clearance <60ml/min
History of retinopathy or maculopathy
Contraindication to corticosteroid therapy (hypersensitivity of active substancies, infections and progressive virosis, glaucoma, psychotic state not controlled by treatment, live vaccine, uncontrolled diabetes mellitus and hypertension)
Intermittent porphyria (risk of acute porphyria crisis)
Glucose-6-Phosphate Dehydrogenase deficiency
Seropositivity to HIV, HBV, HCV
Systemic corticosteroid therapy or immunosuppressive therapy for at least 7 days in the previous year;
History of treatment with hydroxychloroquine for sarcoidosis;
Current pregnancy,
Breastfeeding,
Patient unable to answer questionnaires despite the presence of a caregiver.
Patient under trustee
Patient under legal protection
Participation in another therapeutic interventional trial within 6 months of inclusion

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

Principal Investigator: Florence JENY, MD, ASSISTANCE PUBLIQUE HOPITAUX DE PARIS, Hôpital Avicenne, Service de Pneumologie
Study Director: Dominique VALEYRE, MD, ASSISTANCE PUBLIQUE HOPITAUX DE PARIS, Hôpital Avicenne, Service de Pneumologie