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

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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Sarcoidosis
• Intervention / Treatment: Drug: Prednisone; Drug: Hydroxychloroquine + Prednisone

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Milano, Italy, 20126
    • Università degli Studi di Milano - Bicocca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Milano Bicocca
• Collaborators: Agenzia Italiana del Farmaco
• Investigators: Principal Investigator: Alberto Pesci, Università Milano Bicocca

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (ACTUAL): July 1, 2013
• Study Completion (ACTUAL): September 1, 2013

Study Registration Dates

• First Submitted: July 10, 2014
• First Submitted That Met QC Criteria: July 24, 2014
• First Posted (ESTIMATE): July 25, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): July 25, 2014
• Last Update Submitted That Met QC Criteria: July 24, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: treatment; lung; hydroxychloroquine; glucocorticoids; sarcoidosis
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Lung Diseases; Lung Diseases, Interstitial; Sarcoidosis, Pulmonary; Sarcoidosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Prednisone; Hydroxychloroquine
• Other Study ID Numbers: HySSAS-FARM639KLZ