Hydroxychloroquine as Steroid-Sparing Agent in Pulmonary Sarcoidosis (HySSAS). A Multicenter, Prospective, Controlled, Randomized Trial.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 94
- 试验地点
- 1
- 主要终点
- 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)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Prednisone (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.
干预措施: Hydroxychloroquine + Prednisone (Drug)
结局指标
主要结局
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)
时间窗: Baseline - After 9 months of treatment
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.
时间窗: 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
次要结局
- 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 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 HbA1c(At 3, 6 and 9 months of therapy)
- Secondary safety endpoint was the number of participants with Serious and Non-Serious Adverse Events(Within the 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)
- Secondary SAFETY endpoint was the change from baseline in clinical laboratory tests (including inflammatory markers)(At 3, 6 and 9 months of therapy)