Hydroxychloroquine as Steroid-Sparing Agent in Pulmonary Sarcoidosis (HySSAS).

Recruitment & Eligibility

Inclusion Criteria

patients between 18 and 70 years
parenchymal pulmonary involvement at Chest X-Ray (CXR) AND one of the follows: physiologic abnormalities on pulmonary function testing and/or respiratory symptoms, and/or exercise-induced abnormalities.

Exclusion Criteria

Unable to understand protocol and to sign informed consent or not suitable candidate to comply with the requirements of this study, in the opinion of the investigator
Cardiac and neurological sarcoidosis or any other organ involvement
End stage lung disease at high-resolution computed tomography (HRCT)
Clinical evidence of active infection
Documented exposure to beryllium
Patients with Forced Expiratory Volume at one second (FEV1) changes after salbutamol inhalation ≥20%
Comorbidity: advanced liver cirrhosis or abnormal liver function, unstable cardiac disease, moderate to severe renal insufficiency, poorly controlled diabetes
Pregnancy or lactation
A tuberculin skin test (5 I.U.) more than 5 mm
Psoriasis
Homozygous glucose-6-phosphatase deficiency
Known hypersensitivity to hydroxychloroquine or 4-aminoquinoline derivatives
Visual field changes attributable to 4-aminoquinolines
Concomitant therapies: any patient enrolled in the study must be off all prohibited medications at least 4 weeks before screening. Once patients completed the washout period, they may enter the screening period that may last up to 30 days
Previous therapies: any patient enrolled must be off all medications for sarcoidosis at least 4 weeks before screening.

Study & Design

Arm && Interventions

Group	Intervention	Description
Hydroxychloroquine + Prednisone	Hydroxychloroquine + Prednisone	Hydroxychloroquine per os 200 mg/die (or adjusted for body weight if less than 61 kg), twice/day + prednisone 0,15 mg/kg per os daily, once/day for 3 months, than for further 6 months between responders.
Prednisone	Prednisone	Prednisone per os 0,5 mg/kg/die once/day for 3 months. After 3 months, between responders, prednisone was slowly tapered (5 mg/week maintaining the new reduced dose for one week) to 0,2 mg/kg/die for further 6 months.

Primary Outcome Measures

Name	Time	Method
The primary EFFICACY measure is the per-subject overall success rate at the 3 month visit. Overall response is defined as a combined radiographic and clinical responses.	Baseline- After 3 months of treatment	Subjects is considered clinically cured at the 3 month visit if they will have radiographic success (determined if Chest X-Ray is resolved or improved compared to the baseline; improvement was assessed if there were reduction in hilar adenopathies, less pulmonary involvement, changing in radiographic stage) PLUS a change in at least one of the followings: symptoms (determined by dyspnea or cough index score decrease compared to the baseline), and/or functional improvement (determined by an increase in % of predicted Forced Vital Capacity and/or increase in % of predicted Single-Breath Diffusion capacity of Lung for Carbon monoxide DLCO-SB compared to the baseline), and/or increase in resting Partial pressure of Oxygen in the artery blood (PaO2), and/or worst oxygen saturation increase during 6 Minute Walk Test (6MWT) and/or increase in distance walked at 6MWT, compared to the baseline
The primary SAFETY endpoint is the percent change in lumbar spine (L1-L4) bone mineral density from baseline to month 9 as measured by Dual energy X-ray Absorptiometry (DXA)	Baseline - After 9 months of treatment

Secondary Outcome Measures

Name	Time	Method
Secondary SAFETY endpoint was the change from baseline in Body Mass Index	Baseline - After 3, 6 and 9 months
Secondary SAFETY endpoint was the change from baseline in bone turnover markers and mineral metabolism	At months 3 and 9 from the start of therapy
Secondary SAFETY endpoint was the change from baseline in HbA1c	At 3, 6 and 9 months of therapy
Secondary safety endpoint was the number of participants with Serious and Non-Serious Adverse Events	Within the 9 months of therapy
Secondary EFFICACY endpoint was the change from baseline in radiographic success rate after 9 month of therapy (measured by High Resolution Chest Tomography HRCT)	Baseline- After 9 months of therapy	The radiographic success is determined if HRCT is resolved or improved compared to the baseline after 9 months
Secondary SAFETY endpoint was the change from baseline in clinical laboratory tests (including inflammatory markers)	At 3, 6 and 9 months of therapy

Recruitment & Eligibility