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

NCT05247554 | Unknown Phase 3 DMC

• 2 other identifiers: APHP1911052021-001834-20
• Study Type: interventional
• Target: 200
• Locations: 0 countries
• Sites: N/A

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. "

Conditions

Pulmonary Sarcoidosis

Keywords

Sarcoidosis; Hydroxychloroquine; Pulmonary; Quality of life; Steroids

Outcome Measures

Primary Outcomes (1)

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

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

  6 months

Study Arms (2)

Hydroxychloroquine+low-dose prednisone

EXPERIMENTAL

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

Medium-dose prednisone

ACTIVE COMPARATOR

"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

Interventions

Hydroxychloroquine + low-dose prednisone DRUG

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

Also known as: Experimental Arm

Hydroxychloroquine+low-dose prednisone

Prednisone DRUG

"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 "

Also known as: Standard Arm

Medium-dose prednisone

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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,

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Related Publications (7)

• Broos CE, Wapenaar M, Looman CWN, In 't Veen JCCM, van den Toorn LM, Overbeek MJ, Grootenboers MJJH, Heller R, Mostard RL, Poell LHC, Hoogsteden HC, Kool M, Wijsenbeek MS, van den Blink B. Daily home spirometry to detect early steroid treatment effects in newly treated pulmonary sarcoidosis. Eur Respir J. 2018 Jan 18;51(1):1702089. doi: 10.1183/13993003.02089-2017. Print 2018 Jan. No abstract available.

  PMID: 29348185 BACKGROUND

• Crouser ED, Maier LA, Wilson KC, Bonham CA, Morgenthau AS, Patterson KC, Abston E, Bernstein RC, Blankstein R, Chen ES, Culver DA, Drake W, Drent M, Gerke AK, Ghobrial M, Govender P, Hamzeh N, James WE, Judson MA, Kellermeyer L, Knight S, Koth LL, Poletti V, Raman SV, Tukey MH, Westney GE, Baughman RP. Diagnosis and Detection of Sarcoidosis. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020 Apr 15;201(8):e26-e51. doi: 10.1164/rccm.202002-0251ST.

  PMID: 32293205 BACKGROUND

• Khan NA, Donatelli CV, Tonelli AR, Wiesen J, Ribeiro Neto ML, Sahoo D, Culver DA. Toxicity risk from glucocorticoids in sarcoidosis patients. Respir Med. 2017 Nov;132:9-14. doi: 10.1016/j.rmed.2017.09.003. Epub 2017 Sep 8.

  PMID: 29229111 BACKGROUND

• Baughman RP, Barriuso R, Beyer K, Boyd J, Hochreiter J, Knoet C, Martone F, Quadder B, Richardson J, Spitzer G, Valeyre D, Ziosi G. Sarcoidosis: patient treatment priorities. ERJ Open Res. 2018 Dec 21;4(4):00141-2018. doi: 10.1183/23120541.00141-2018. eCollection 2018 Oct.

  PMID: 30588477 BACKGROUND

• Ponticelli C, Moroni G. Hydroxychloroquine in systemic lupus erythematosus (SLE). Expert Opin Drug Saf. 2017 Mar;16(3):411-419. doi: 10.1080/14740338.2017.1269168. Epub 2016 Dec 14.

  PMID: 27927040 BACKGROUND

• Baltzan M, Mehta S, Kirkham TH, Cosio MG. Randomized trial of prolonged chloroquine therapy in advanced pulmonary sarcoidosis. Am J Respir Crit Care Med. 1999 Jul;160(1):192-7. doi: 10.1164/ajrccm.160.1.9809024.

  PMID: 10390399 BACKGROUND

• Judson MA, Baughman RP, Costabel U, Flavin S, Lo KH, Kavuru MS, Drent M; Centocor T48 Sarcoidosis Investigators. Efficacy of infliximab in extrapulmonary sarcoidosis: results from a randomised trial. Eur Respir J. 2008 Jun;31(6):1189-96. doi: 10.1183/09031936.00051907. Epub 2008 Feb 6.

  PMID: 18256069 BACKGROUND

MeSH Terms

Conditions

Sarcoidosis, Pulmonary; Sarcoidosis

Interventions

Hydroxychloroquine; Prednisone

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Florence JENY, MD

  ASSISTANCE PUBLIQUE HOPITAUX DE PARIS, Hôpital Avicenne, Service de Pneumologie

  PRINCIPAL INVESTIGATOR

• Dominique VALEYRE, MD

  ASSISTANCE PUBLIQUE HOPITAUX DE PARIS, Hôpital Avicenne, Service de Pneumologie

  STUDY DIRECTOR

Central Study Contacts

Florence JENY, MD

CONTACT

+331.48.95.52.80; florence.jeny@aphp.fr

Dominique VALEYRE, MD

CONTACT

dominique.valeyre@aphp.Fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2022
• First Posted: February 21, 2022
• Study Start: March 1, 2022
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2024
• Last Updated: February 21, 2022

Record last verified: 2022-01