NCT04314193进行中（未招募）4 期
The PREDMETH Trial: Effectiveness of Methotrexate Versus Prednisone As First-line Therapy for Pulmonary Sarcoidosis - a Randomized Controlled Trial
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 138
- 试验地点
- 17
- 主要终点
- Forced Vital Capacity (FVC)
研究概览
简要总结
This is a prospective, randomized, non-blinded, multi-center, non-inferiority trial designed to compare effectiveness and side-effects of methotrexate versus prednisone as first-line therapy for pulmonary sarcoidosis.
详细描述
Sarcoidosis is a multisystem, granulomatous disorder, most commonly affecting the lungs. Symptom burden is high, and quality of life (QoL) and social participation are negatively affected. In patients with pulmonary sarcoidosis, treatment is recommended in case of significant symptoms and/or impaired or deteriorating lung function. Evidence-based treatment recommendations are limited, outdated and largely based on expert opinion.
Prednisone is currently the first-choice therapy in pulmonary sarcoidosis and leads to short-term improvement of lung function. Unfortunately, prednisone has major side-effects and is associated with impaired QoL. Methotrexate is presently considered second-line therapy, and appears to have fewer side-effects. The investigators hypothesize that first-line treatment with methotrexate is as effective as prednisone, with fewer side-effects and better QoL.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of sarcoidosis according to the ATS/ERS/WASOG criteria, in case of absent histology a diagnosis of sarcoidosis can also be established in a multidisciplinary team meeting in a sarcoidosis expert center based on a highly suggestive clinical and radiological picture.
- •Age ≥18 years.
- •A pulmonary indication for treatment and parenchymal involvement on X-ray or CT-scan conducted within three months before inclusion (determined by the treating physician and conform current guidelines).
- •A forced vital capacity (FVC) of ≤90% of predicted, or a diffusion capacity of the lung for carbon monoxide (DLCO) ≤70% of predicted, or ≥5% FVC absolute decline/≥10% DLCO absolute decline in the past year. For pulmonary functions tests GLI reference values are used.
排除标准
- •Any condition or circumstance that, in the opinion of the investigator, may make a subject unlikely or unable to complete the study or comply with study procedures.
- •Previous immunosuppressive treatment for sarcoidosis
- •Use of systemic immunosuppressive therapy within the preceding three months for another disease than sarcoidosis
- •Pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study treatment or within 90 days after the last dose in the randomized study phase. For males; planning to pro-create during the study or within 90 days after the last dose of the randomized study phase.
- •Primary systemic treatment indication being an extra pulmonary location of sarcoidosis (e.g. cardiac of neurological)
- •Contra-indication for methotrexate or corticosteroids:
- •severely impaired renal function (creatinine clearance <30 ml/min)
- •impaired hepatic function (serum bilirubin-value >5 mg/dl or 85,5 micromole/l)
- •bone marrow insufficiency with severe leukopenia, thrombocytopenia, or anaemia
- •severe acute or chronic infections, such as tuberculosis, HIV, parasitic infections or other immunodeficiency syndromes
- •mouth, stomach or duodenal ulcers
研究组 & 干预措施
methotrexate
Experimental
干预措施: Methotrexate (Drug)
prednisone
Active Comparator
干预措施: Prednisone (Drug)
结局指标
主要结局
Forced Vital Capacity (FVC)
时间窗: 24 weeks after inclusion
Change in hospital-measured FVC between baseline and 24 weeks
次要结局
- Forced Vital Capacity (FVC)(16 weeks)
- Time to major pulmonary improvement measured by FVC(24 weeks)
- Change in FVC(24 weeks)
- Change in DLCO(24 weeks)
- Changes in Angiotensin-Converting Enzyme (ACE)(2 years)
- Between group changes in sACE levels during treatment(2 years)
- Changes in soluble interleukin-2 receptor (sIL-2R)(2 years)
- Between group changes in sIL-2R levels during treatment(2 years)
- Changes in extracellular vesicles during treatment(2 years)
- Between group changes in extracellular vesicles absolute numbers(2 years)
- Changes in protein expression levels in extracellular vesicles during treatment(2 years)
- Between group changes in protein expression levels in extracellular vesicles(2 years)
- Changes in T lymphocyte phenotypes during Treatment(2 years)
- Between group changes in T lymphocyte phenotypes(2 years)
- Changes in T lymphocyte absolute cell numbers(2 years)
- Between group changes in T lymphocyte absolute cell numbers(2 years)
- Changes in the distribution of T lymphocytes during treatment(2 years)
- Between group changes in the distribution of T lymphocytes(2 years)
- Changes in dendritic cell phenotypes during Treatment(2 years)
- Between group changes in dendritic cell phenotypes(2 years)
- Changes in dendritic cell absolute cell numbers(2 years)
- Between group changes in dendritic cell absolute cell numbers(2 years)
- Changes in the distribution of dendritic cells during treatment(2 years)
- Between group changes in the distribution of dendritic cells(2 years)
- Changes in monocyte subset phenotypes during Treatment(2 years)
- Between group changes in monocyte subset phenotypes(2 years)
- Changes in monocyte absolute cell numbers(2 years)
- Between group changes in monocyte absolute cell numbers(2 years)
- Changes in the distribution of monocytes during treatment(2 years)
- Between group changes in the distribution of monocytes(2 years)
- Correlation between biomarkers and clinical parameters(2 years)
- The King's Sarcoidosis Questionnaire (KSQ)(baseline and 2 years after inclusion)
- The Chronic Respiratory Questionnaire (CRQ)(baseline and 2 years after inclusion)
- The global rating of change scale (GRC)(baseline and 2 years after inclusion)
- The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)(baseline and 2 years after inclusion)
- The Medical Research Council Dyspnea scale(Baseline and 2 years after inclusion)
- The fatigue assessment scale (FAS)(Baseline and 2 years after inclusion)
- Number of patients who discontinue/switch medication(During 24 weeks)
- Patient Experience and Satisfaction with Medication questionnaire(2 years)
研究者
Marlies Wijsenbeek
Principal investigator
Erasmus Medical Center
研究点 (17)
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