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

Phase

Condition

Sarcoidosis

Lung Disease

Treatment

N/A

Clinical Study ID

NCT05247554

APHP191105

2021-001834-20

Ages 18-80
All Genders

Study 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. "

Eligibility Criteria

Inclusion

Inclusion Criteria:

Age between 18-80 years old
Pulmonary sarcoidosis meeting the diagnostic criteria form ATS 2020 AJRCCM diagnosticcriteria.
Patient with radiographic stage II (mediastinal-hilar bilateral lymphadenopathy andparenchymal involvement) or III (involvement pulmonary parenchymatous) and FVC<80% andrespiratory 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

Exclusion Criteria:

Severe impairment requiring an immediate and urgent result and/or high doses ofcorticosteroids (neurological, cardiac, ophthalmic (severe uveitis with ocularsequala), 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 toexcipients, 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 bytreatment, 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 inthe 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 Design

March 01, 2022

March 01, 2024

Study 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. "