A European Multi-center, Randomised, Double-blind Trial of Pirfenidone in Bronchiolitis-obliterans-syndrome Grade 1-3 in Lung Transplant Recipients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 90
- 试验地点
- 9
- 主要终点
- To evaluate the effect of Pirfenidone on the change in FEV1 in liters over 6 months in lung transplant recipients with bronchiolitis obliterans syndrome.
研究概览
简要总结
A European multi-centre, randomised, double-blind placebo-controlled trial of Pirfenidone in bronchiolitis-obliterans-syndrome grade 1-3 in lung transplant recipients.
Randomized double blinded, placebo controlled study. Eligible patients are to be randomized in a 1:1 ratio to receive either Pirfenidone 2403 mg/d or the matching placebo treatment for 6 months.
Primary objective To evaluate the effect of Pirfenidone on the change in FEV1 in liters over 6 months in lung transplant recipients with bronchiolitis obliterans syndrome.
详细描述
Title of the study: A European multi-centre, randomised, double-blind placebo-controlled trial of Pirfenidone in bronchiolitis-obliterans-syndrome grade 1-3 in lung transplant recipients
Study design: Randomized double blinded, placebo controlled study. Eligible patients are to be randomized in a 1:1 ratio to receive either Pirfenidone 2403 mg/d or the matching placebo treatment for 6 months.
Study objectives Primary objective:
Change in FEV1 in liters over 6 months in lung transplant recipients with bronchiolitis obliterans syndrome.
Secondary objectives:
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
- Triple (Participant, Care Provider, Investigator)
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
- •Patients >18 years of age
- •Azithromycin therapy for at least 4 weeks prior to study start, with an Azithromycin dose of minimum 250 mg/day at least 3 times per week as this is considered standard therapy for bronchiolitis obliterans syndrome.
- •Double lung transplantation is required.
- •Patients must be at least 6 months after transplantation and must have documented post-transplant baseline value of FEV1 (mean of the 2 highest values measured at least 3 weeks apart according to ISHLT criteria).
- •Patients must have BOS grade 1 to BOS grade
- •Patients must have documented progressive disease as demonstrated by all of the following criteria:
- •Patients must have at least 3 FEV1-measurements in the last 6 months, each at least 3 weeks apart
- •a total decline of at least 200ml in FEV1 i
- •a decline of at least 50 ml in the last two measurements
- •Exclusion Criteria
- •Patients with lung redo transplantation, combined transplantation (including heart and lung transplantation) or single lung recipients.
- •Patients with any severe comorbidity complicating BOS which might determine the prognosis and functional level of the patient (e.g. invasive aspergillosis, active malignant disease) within the last 12 months.
- •FEV1 decline related to other non BOS causes (eg pneumothorax, bronchial stenosis, effusion, etc.)
- •Patients who have developed BOS grade
- •Patients who on Thorax CT at entry demonstrate new significant findings which are not compatible with BOS like interstitial fibrosis, consolidation, appearances suggesting Restrictive Allograft Syndrome (RAS) and acute pulmonary infection as cause of decline in lung function.
- •Documented acute perivascular rejection higher than grade A1 or findings compatible with antibody mediated rejection
- •Pregnancy or lactation (women of childbearing capacity are required to have a negative serum pregnancy test before treatment and must agree to maintain highly effective contraception by practicing abstinence or by using at least two methods of birth control from the date of consent through the end of the study).
- •Renal insufficiency (Creatinine clearance <30 ml/min calculated by the CKD-Epi formula.
- •Any of the following liver test criteria above the specified limit:
- •Total bilirubin above the upper limit of the normal range (ULN), except in patients with predominantly unconjugated hyperbilirubinemia (e.g., Gilbert's syndrome)
- •Aspartate or alanine aminotransferase (AST or ALT) >3 × ULN
- •Known allergy or hypersensitivity to Pirfenidone
- •Ongoing use or expected use of any of the following therapies:
- •Strong inhibitors of CYP1A2 (e.g. fluvoxamine or enoxacin)
- •Moderate inhibitors of CYP1A2 (e.g. mexiletine, thiabendazole, or phenylpropanolamine [Note: ciprofloxacin will be allowed only at doses ≤500 mg BID])
- •Previous treatment with Pirfenidone after transplantation
- •Patients who have resumed smoking after transplantation
排除标准
- 未提供
研究组 & 干预措施
Placebo
Receive placebo tablets
干预措施: Placebo (Drug)
Pirfenidone
Upon enrollment, subjects will be randomized to either the treatment group (Pirfenidone) or to the placebo group (1:1 ratio). The trial medication will be administered as 267-mg oral capsules and titrated to a maintenance dose of 2403 mg/d (3 capsules TID, for a total of 9 capsules/day).
干预措施: Pirfenidone (Drug)
结局指标
主要结局
To evaluate the effect of Pirfenidone on the change in FEV1 in liters over 6 months in lung transplant recipients with bronchiolitis obliterans syndrome.
时间窗: 6 months
次要结局
- - Change in QoL as assessed by EQ5D(6 months)
- - Categorical percentage change in FEV1(6 months)
- - Change in Forced Vital Capacity (FVC)(6 months)
- - Change in Total Lung Capacity (TLC)(6 months)
- - Change in FEV1/FVC ratio(6 months)
- - Number of patients with treatment failure(6 months)
- - Change in functional level as assessed by the 6MWT(6 months)
- - Hospital admission for any reason(6 months)
- - Change in BOS grade(6 months)
- - Change in percent predicted diffusion capacity (DLCO)(6 months)
- - Death or re-transplantation rates(6 months)
研究者
Michael Perch
Medical Director Danish National Lung Transplant Program
Rigshospitalet, Denmark