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

February 9, 2022 updated by: Assistance Publique - Hôpitaux de Paris

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

"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. "

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

200

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in percentage of the predicted forced vital capacity (FVC) between inclusion and 6 months
Time Frame: 6 months
"Difference in percentage of the predicted forced vital capacity (FVC) between inclusion and 6 months "
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

March 1, 2022

Primary Completion (Anticipated)

March 1, 2023

Study Completion (Anticipated)

March 1, 2024

Study Registration Dates

First Submitted

February 9, 2022

First Submitted That Met QC Criteria

February 9, 2022

First Posted (Actual)

February 21, 2022

Study Record Updates

Last Update Posted (Actual)

February 21, 2022

Last Update Submitted That Met QC Criteria

February 9, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APHP191105
  • 2021-001834-20 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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