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

Study Overview
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Brief Summary
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The aim of the study is determining the non-inferiority in the overall success rate and the safety for a combination therapy with hydroxychloroquine plus low dose glucocorticoids compared to that for high dose glucocorticoids at 3 and 9 months in patients with pulmonary sarcoidosis.

Official Title
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Hydroxychloroquine as Steroid-Sparing Agent in Pulmonary Sarcoidosis (HySSAS). A Multicenter, Prospective, Controlled, Randomized Trial.

Conditions
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Pulmonary Sarcoidosis

Intervention / Treatment
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* Drug: Prednisone
* Drug: Hydroxychloroquine + Prednisone


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Prednisone<br>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. | Drug: Prednisone<br>* 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.<br>|
| Experimental: Hydroxychloroquine + Prednisone<br>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. | Drug: Hydroxychloroquine + Prednisone<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 | Baseline- After 3 months of treatment | 
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary EFFICACY endpoint was the change from baseline in radiographic success rate after 9 month of therapy (measured by High Resolution Chest Tomography HRCT) | The radiographic success is determined if HRCT is resolved or improved compared to the baseline after 9 months | Baseline- After 9 months of therapy | 
| 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 HbA1c |  | At 3, 6 and 9 months of therapy | 
| Secondary SAFETY endpoint was the change from baseline in clinical laboratory tests (including inflammatory markers) |  | At 3, 6 and 9 months of therapy | 
| 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 number of participants with Serious and Non-Serious Adverse Events |  | Within the 9 months of therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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treatment, lung, glucocorticoids, hydroxychloroquine, sarcoidosis