Pulmonary Sarcoidosis
Conditions
Keywords
sarcoidosis, treatment, lung, glucocorticoids, hydroxychloroquine
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.
Interventions
DRUGPrednisone
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.
DRUGHydroxychloroquine + 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.
Sponsors
Agenzia Italiana del Farmaco
University of Milano Bicocca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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 |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 EFFICACY endpoint was the change from baseline in radiographic success rate after 9 month of therapy (measured by High Resolution Chest Tomography HRCT) | Baseline- After 9 months of therapy | The radiographic success is determined if HRCT is resolved or improved compared to the baseline after 9 months |
| Secondary safety endpoint was the number of participants with Serious and Non-Serious Adverse Events | Within the 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 change from baseline in Body Mass Index | Baseline - After 3, 6 and 9 months | — |
Countries
Italy
Outcome results
None listed