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

Pulmonary Sarcoidosis Clinical Trial

— HySSAS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02200146
• Other study ID #: HySSAS-FARM639KLZ
• Status: Completed
• Phase: Phase 3
• First received: July 10, 2014
• Last updated: July 24, 2014
• Start date: March 2009
• Est. completion date: September 2013

Study information

• Verified date: July 2014
• Source: University of Milano Bicocca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 94
• Est. completion date: September 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pulmonary Sarcoidosis
• Sarcoidosis
• Sarcoidosis, Pulmonary

Intervention

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.
• 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.

Locations

Country	Name	City	State
Italy	Università degli Studi di Milano - Bicocca	Milano

Sponsors (2)

Lead Sponsor	Collaborator
University of Milano Bicocca	Agenzia Italiana del Farmaco

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	Yes
Secondary	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	No
Secondary	Secondary SAFETY endpoint was the change from baseline in Body Mass Index		Baseline - After 3, 6 and 9 months	Yes
Secondary	Secondary SAFETY endpoint was the change from baseline in HbA1c		At 3, 6 and 9 months of therapy	Yes
Secondary	Secondary SAFETY endpoint was the change from baseline in clinical laboratory tests (including inflammatory markers)		At 3, 6 and 9 months of therapy	Yes
Secondary	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	Yes
Secondary	Secondary safety endpoint was the number of participants with Serious and Non-Serious Adverse Events		Within the 9 months of therapy	Yes