search
Back to results

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

Primary Purpose

Pulmonary Sarcoidosis

Status
Completed
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
Prednisone
Hydroxychloroquine + Prednisone
Sponsored by
University of Milano Bicocca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Sarcoidosis focused on measuring sarcoidosis, treatment, lung, glucocorticoids, hydroxychloroquine

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Università degli Studi di Milano - Bicocca

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Prednisone

Hydroxychloroquine + Prednisone

Arm Description

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 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.

Outcomes

Primary Outcome Measures

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
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)

Secondary Outcome Measures

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
Secondary SAFETY endpoint was the change from baseline in Body Mass Index
Secondary SAFETY endpoint was the change from baseline in HbA1c
Secondary SAFETY endpoint was the change from baseline in clinical laboratory tests (including inflammatory markers)
Secondary SAFETY endpoint was the change from baseline in bone turnover markers and mineral metabolism
Secondary safety endpoint was the number of participants with Serious and Non-Serious Adverse Events

Full Information

First Posted
July 10, 2014
Last Updated
July 24, 2014
Sponsor
University of Milano Bicocca
Collaborators
Agenzia Italiana del Farmaco
search

1. Study Identification

Unique Protocol Identification Number
NCT02200146
Brief Title
Hydroxychloroquine as Steroid-Sparing Agent in Pulmonary Sarcoidosis (HySSAS).
Acronym
HySSAS
Official Title
Hydroxychloroquine as Steroid-Sparing Agent in Pulmonary Sarcoidosis (HySSAS). A Multicenter, Prospective, Controlled, Randomized Trial.
Study Type
Interventional

2. Study Status

Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Milano Bicocca
Collaborators
Agenzia Italiana del Farmaco

4. Oversight

Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Sarcoidosis
Keywords
sarcoidosis, treatment, lung, glucocorticoids, hydroxychloroquine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
94 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Prednisone
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Hydroxychloroquine + Prednisone
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine + Prednisone
Intervention Description
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.
Primary Outcome Measure Information:
Title
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.
Description
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
Time Frame
Baseline- After 3 months of treatment
Title
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 Measure Information:
Title
Secondary EFFICACY endpoint was the change from baseline in radiographic success rate after 9 month of therapy (measured by High Resolution Chest Tomography HRCT)
Description
The radiographic success is determined if HRCT is resolved or improved compared to the baseline after 9 months
Time Frame
Baseline- After 9 months of therapy
Title
Secondary SAFETY endpoint was the change from baseline in Body Mass Index
Time Frame
Baseline - After 3, 6 and 9 months
Title
Secondary SAFETY endpoint was the change from baseline in HbA1c
Time Frame
At 3, 6 and 9 months of therapy
Title
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
Title
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
Title
Secondary safety endpoint was the number of participants with Serious and Non-Serious Adverse Events
Time Frame
Within the 9 months of therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alberto Pesci
Organizational Affiliation
Università Milano Bicocca
Official's Role
Principal Investigator
Facility Information:
Facility Name
Università degli Studi di Milano - Bicocca
City
Milano
ZIP/Postal Code
20126
Country
Italy

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs