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

• ClinicalTrials.gov Identifier: NCT02200146
• Recruitment Status: Completed
• First Posted: July 25, 2014
• Last Update Posted: July 25, 2014
• Sponsor: University of Milano Bicocca
• Collaborator: Agenzia Italiana del Farmaco
• Information provided by (Responsible Party): University of Milano Bicocca

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pulmonary Sarcoidosis	Drug: Prednisone; Drug: Hydroxychloroquine + Prednisone	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 94 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Hydroxychloroquine as Steroid-Sparing Agent in Pulmonary Sarcoidosis (HySSAS). A Multicenter, Prospective, Controlled, Randomized Trial.
• Study Start Date: March 2009
• Actual Primary Completion Date: July 2013
• Actual Study Completion Date: September 2013

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 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.	Drug: 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.
Experimental: 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.	Drug: 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.

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: 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
2. 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) [ Time Frame: Baseline - After 9 months of treatment ]

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Italy

Università degli Studi di Milano - Bicocca

Milano, Italy, 20126

Sponsors and Collaborators

University of Milano Bicocca

Agenzia Italiana del Farmaco

Investigators

• Principal Investigator: Alberto Pesci; Università Milano Bicocca

More Information

• Responsible Party: University of Milano Bicocca
• ClinicalTrials.gov Identifier: NCT02200146
• Other Study ID Numbers: HySSAS-FARM639KLZ
• First Posted: July 25, 2014
• Last Update Posted: July 25, 2014
• Last Verified: July 2014

Keywords provided by University of Milano Bicocca:

sarcoidosis; treatment; lung; glucocorticoids; hydroxychloroquine

Additional relevant MeSH terms:

Sarcoidosis, Pulmonary; Sarcoidosis; Prednisone; Lymphoproliferative Disorders; Lymphatic Diseases; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Hydroxychloroquine; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Anti-Infective Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents