Randomized Controlled Trial Testing the Efficacy of Corticosteroid Therapy Versus Placebo in Fibrotic Hypersensitivity Pneumonitis": RUBY Study (Randomised Trial, glUcocorticoids Versus placeBo in Fibrotic hYpersensitivity Pneumonitis)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 120
- 主要终点
- Absolute change in FVC (% pred)
研究概览
简要总结
Hypersensitivity Pneumonitis (HP) is an immune-mediated disease that manifests as interstitial lung disease after exposure to an inhaled antigen, often unidentified. HP can be classified as non-fibrotic or fibrotic HP. Fibrotic HP is associated with impaired quality of life (QoL) and reduced survival. The value and decline of forced vital capacity (FVC) are predictive factors of mortality in fibrotic HP. In most expert centres worldwide, corticosteroids are chosen as the first-line drug to treat fibrotic HP in clinical practice. However, this strategy has not been validated in a randomized controlled trial and it remains controversial, Moreover, corticosteroids are responsible for potentially serious adverse events. The hypothesis is that prednisolone, as a first-line treatment in fibrotic hypersensitivity pneumonitis (HP), slows down FVC decline compared to placebo.
The main objective is to assess the efficacy of first-line treatment with prednisolone against placebo, on the 6-month change in FVC in percent of predicted value (% pred).The primary endpoint will be the absolute change in FVC (% pred) from baseline (inclusion visit,M0) to 6 months (M6) will be compared between the placebo arm and the prednisolone arm.
详细描述
Hypersensitivity Pneumonitis (HP) is an immune-mediated disease that manifests as interstitial lung disease after exposure to an inhaled antigen, often unidentified. HP can be classified as non-fibrotic or fibrotic HP. Fibrotic HP is associated with impaired quality of life (QoL) and reduced survival. The value and decline of forced vital capacity (FVC) are predictive factors of mortality in fibrotic HP. In most expert centres worldwide, corticosteroids are chosen as the first-line drug to treat fibrotic HP in clinical practice. However, this strategy has not been validated in a randomized controlled trial and it remains controversial, Moreover, corticosteroids are responsible for potentially serious adverse events. The hypothesis is that prednisolone, as a first-line treatment in fibrotic hypersensitivity pneumonitis (HP), slows down FVC decline compared to placebo.
The main objective is to assess the efficacy of first-line treatment with prednisolone against placebo, on the 6-month change in FVC in percent of predicted value (% pred).The primary endpoint will be the absolute change in FVC (% pred) from baseline (inclusion visit,M0) to 6 months (M6) will be compared between the placebo arm and the prednisolone arm.
RUBY, is a national multicenter, randomized, double blind, placebo-controlled, superiority trial comparing the efficacy of prednisolone to placebo on the change in FVC (% pred) at 6 months.
The investigators will randomly assign participants (1:1 ratio, stratification according to the identification of an inciting antigen) to receive oral prednisolone or placebo for a period of 6 months with a follow-up of 12 months. The primary endpoint will be assessed at Month 6.
The investigators plan to include 120 participants.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient aged above 18 years and under 90 years old
- •Diagnosis of fibrotic HP ("definite" or "high confidence") after MDD according to the criteria proposed by guidelines [5]
- •Fibrosis extent ≥ 10% on chest HRCT
- •Mild to moderate functional impairment defined by FVC ≥ 50% pred and DLco ≥ 30% pred
- •Written informed consent for participation in study
- •Patient affiliated to a social security scheme or CMU beneficiary
- •Effective contraception for men and woman of childbearing age.
排除标准
- •Uncertain diagnosis of fibrotic HP ("low confidence" or "unlikely") after MDD according to the criteria proposed by guidelines [5].
- •Severe functional impairment defined by FVC < 50% pred and DLco < 30% pred.
- •Patient previously treated or currently being treated for fibrotic HP (with corticosteroids, any immunosuppressive agent, or anti- fibrotic therapies).
- •Person under guardianship/ curatorship (sous tutelle/curatelle)
- •Contraindication to corticosteroid therapy (hypersensitivity to the active substances or to one of the excipients, severe infections, psychotic states not controlled by treatment, live vaccines, uncontrolled diabetes mellitus and uncontrolled arterial hypertension.) or to auxiliary medicinal products
- •Patient deprived of liberty under judicial or administrative decision
- •Patient participating in another clinical trial with an investigational medicinal product. The patient may participate in another clinical trial after the 6 months of treatment in this study
- •Pregnancy or breastfeeding woman
- •Patient receiving AME (state medical assistance)
研究组 & 干预措施
Prednisolone (oral)
Prednisolone (oral) will be administered and tapered over 6 months, according to the schedule detailed in the protocol(Cumulative dose: 2430mg/ 6months).
Active Comparator: prednisolone. Oral prednisolone will be administered and tapered over 6 months, according to the following schedule: 0.5 mg/kg/day (not exceeding 40mg/day) x 4 weeks, 0.25 mg/kg/day (not exceeding 20mg/day) x 4 weeks, 15 mg/day x 4 weeks, 10 mg/days x 4 weeks, 5 mg/day x 10 weeks
干预措施: Prednisolone (Drug)
Placebo
Dispersible placebo administered and tapered over 6 months according to the schedule detailed in the protocol
干预措施: Placebo (Drug)
结局指标
主要结局
Absolute change in FVC (% pred)
时间窗: at month 6
Absolute change in FVC (% pred) from baseline (inclusion visit, M0) to 6 months (M6) will be compared between the placebo arm and the prednisolone arm.
次要结局
- Absolute change in FVC (% pred) according to the presence of a causal antigen at Month 6(at Month 6)
- The change in FVC (% pred) at 12 months (M12)(At month 12)
- The change in FVC (mL) at 12 months (M12)(At month 12)
- The changes in DLco (mmol/min/kPa) at Month 6(At Month 6)
- The changes in DLco (% pred) at Month 6(At Month 6)
- The changes in DLco (mmol/min/kPa) at Month 12(At Month12)
- The changes in DLco (% pred) at Month 12(At Month 12)
- The changes in distance walked during six-minute walt test 6MWT in meters (m) at Month 12(at Month12)
- The changes in distance walked during six-minute walt test 6MWT (% pred) at Month 12(At Month 12)
- The changes in distance walked during six-minute walt test 6MWT in meters (m) at Month 6(At Month 6)
- The changes in distance walked during six-minute walt test 6MWT (%pred) at Month 6(At Month 6)
- The change in health related QoL (the Saint Georges Hospital Respiratory Questionnaire (SGRQ) at Month 6(At Month 6)
- The change in health related QoL (King's Brief ILD questionnaire) at Month 6(At Month 6)
- The change in health related QoL (the Saint Georges Hospital Respiratory Questionnaire (SGRQ) at Month 12(At Month 12)
- The change in health related QoL (King's Brief ILD questionnaire) at Month 12(At Month 12)
- The proportion of patients who develop pulmonary progressive fibrosis (PPF) within 12 months(Over 12 months)
- The proportion of subjects who experience acute exacerbation (AE) or require unplanned hospitalization within 12 months(Over 12 months)
- Progression free survival (PFS) at 12 months(At month 12)