Mycophenolate Mofetil and Prednisolone Versus Prednisolone Alone in Fibrotic Hypersensitivity Pneumonitis: a Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 144
- 试验地点
- 10
- 主要终点
- Lung function (FVC) decline
研究概览
简要总结
To our knowledge, there is no randomized controlled trial assessing the efficacy of mycophenolate mofetil (MMF) in the treatment of HP. We aim to perform a randomized study to assess the efficacy and safety of a regimen consisting of MMF and prednisolone against a regimen consisting of prednisolone alone for treating fibrotic HP. We hypothesize that the treatment of patients with fibrotic HP with MMF and prednisolone will be more effective and safer than treatment with prednisolone alone.
详细描述
Hypersensitivity pneumonitis (HP) is a complex immunologically-mediated interstitial lung disease (ILD) resulting from sensitization to an inhaled antigen. It may be categorized into acute (acute/subacute) or chronic forms based on the duration of disease or evidence of chronicity on radiological or pathological findings. Lately, the American Thoracic Society (ATS) Guidelines 2020 has endorsed a new classification of HP into non-fibrotic and fibrotic types based on the absence or presence of signs of fibrosis on chest computed tomography (CT) or histology. According to a survey study, about three-fourths of respiratory physicians believe that fibrotic HP should be treated with glucocorticoids as the treatment of first choice, which also reflects the practice in most centers worldwide. However, there is some evidence that glucocorticoids may not be effective in the long-term treatment of fibrotic HP. Also, glucocorticoids are associated with several adverse effects especially when used over a long duration. Therefore, most experts recommend that glucocorticoids should be tapered to the lowest possible dose after a trial of about three months in chronic/fibrotic HP.
Hypersensitivity pneumonitis is characterized by an exaggerated T cell-mediated immune inflammatory response (T-lymphocytic alveolitis) due to increased migration, local proliferation, and decreased programmed cell death of lymphocytes. Mycophenolate mofetil (MMF) is an immunosuppressive drug that acts by inhibiting the proliferation of T-lymphocytes and suppressing the recruitment of lymphocytes and monocytes into the sites of inflammation. Therefore, MMF is likely to be effective in the treatment of HP. There are only a few retrospective studies on the efficacy of MMF in the treatment of HP. To our knowledge, there is no randomized controlled trial assessing the efficacy of MMF in the treatment of HP.
We aim to perform a randomized study to assess the efficacy and safety of a regimen consisting of MMF and prednisolone against a regimen consisting of prednisolone alone for treating fibrotic HP. We hypothesize that the treatment of patients with fibrotic HP with MMF and prednisolone will be more effective and safer than treatment with prednisolone alone.
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
- •i. A diagnosis of fibrotic hypersensitivity pneumonitis according to the criteria proposed in the American Thoracic Society Guideline 2020 ii. Screening FVC at least 40% of the predicted value iii. Able to provide a written, informed consent for participation in the trial
排除标准
- •i. Baseline FVC <40% predicted ii. Leucopenia (white blood cell count <4·0 × 10^9 per L), significant thrombocytopenia (platelet count <100 × 10^9 per L), or clinically significant anemia (hemoglobin <10 g/dL) iii. Baseline liver transaminases (alanine aminotransferase and aspartate aminotransferase) or bilirubin more than 1·5 times the upper normal limit (except in the case of Gilbert's syndrome) iv. Serum creatinine higher than 2.0 mg/dL v. Uncontrolled congestive heart failure vi. Receipt of prednisolone (more than or equal to 10 mg/day, or equivalent), in the 4 weeks before randomization vii. Prior use of prednisolone (more than or equal to 10 mg/day, or equivalent), MMF, azathioprine, cyclophosphamide, cyclosporine or any other non-glucocorticoid immunosuppressant drug, or antifibrotic agents for more than 12 weeks in the previous year viii. Active infection (lung or elsewhere) whose management would be compromised by MMF or prednisolone ix. Other serious concomitant medical illness (eg, cancer), chronic debilitating illness (other than chronic HP), or drug abuse x. Pregnancy (documented by urine pregnancy test) or breastfeeding xi. Unwilling to participate in the study
研究组 & 干预措施
Mycophenolate mofetil plus prednisolone
Oral prednisolone will be administered according to the schedule in the prednisolone alone arm. Mycophenolate mofetil will be administered starting from 2 weeks after randomization. It will be initiated at a dose of 500 mg twice daily and will be escalated to 1000 mg twice daily after two weeks.
干预措施: Mycophenolate Mofetil plus prednisolone (Drug)
Prednisolone alone
Oral prednisolone will be administered over 52 weeks, according to following schedule 0.75 mg/kg x 2 weeks 0.5 mg/kg x 2 weeks 20 mg/day x 4 weeks 15 mg/day x 4 weeks 10 mg/day x 4 weeks 5 mg/day x 10 weeks 5 mg on alternate days x 26 weeks
干预措施: Prednisolone (Drug)
结局指标
主要结局
Lung function (FVC) decline
时间窗: 52 weeks
Annual rate of decline in forced vital capacity (FVC) assessed using spirometry assessed over 52 weeks
次要结局
- FEV1 decline(52 weeks)
- Disease specific health status(52 weeks)
- Severity of breathlessness(52 weeks)
- Proportion of subjects who develop progressive pulmonary fibrosis (PPF)(52 weeks)
- Proportion of subjects who develop acute exacerbation(s)(52 weeks)
- Treatment-emergent adverse effects(52 weeks)
- Diffusion capacity(52 weeks)
- Six-minute walk distance(52 weeks)
研究者
Sahajal Dhooria
Additional Professor
Post Graduate Institute of Medical Education and Research, Chandigarh