A Phase Two Randomized, Double-blinded, Placebo-controlled Study Combining Physiological, Radiographic, and Biological Biomarkers to Study the Anti-fibrotic Effect of Pirfenidone in CLAD Post Lung-transplantation
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Change in Percent of Functional Small Airways Disease (fSAD) as Measured by Parametric Response Mapping
研究概览
简要总结
Greater than 50% of lung transplant recipients show signs of chronic lung allograft dysfunction (CLAD) by 5 years post-transplantation.Therapies to prevent or slow CLAD are lacking. Anti-fibrotic therapies may offer an avenue to prevent progression of CLAD and prolong allograft survival. This study investigates if Pirfenidone therapy will stabilize lung function decline and slow progression of Functional small airways disease (fSAD) in lung transplant recipients with CLAD.
详细描述
The study aimed to enroll lung transplant recipients with an established diagnosis of CLAD. The patients were randomized to receive an anti-fibrotic drug Pirfenidone or Placebo pills for 6 month period. High-resolution CT scan of the chest was utilized to measure the primary endpoint of change in functional small airway disease (fSAD). Pulmonary function testing and spirometry were utilized to measure the secondary endpoint of change in FEV1 and FVC.
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
- Double (Participant, 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
- •Lung transplant recipients 18 years of age or older
- •Greater than 6 months after single or bilateral lung transplantation
- •Baseline FEV1 and FVC values (mean of two highest value measured 3 weeks apart) > 50% predicted (to assure viable graft)
- •Diagnosis of CLAD (two consecutive spirometric values of FEV1 alone or both FEV1 and FVC < 80% of baseline)
- •Exclusion Criteria
- •Acute Rejection (AR) diagnosis by biopsy in the 28 days prior to enrollment
- •Treatment with pulse steroids, Anti-thymocyte Globulin (ATG), extracorporeal photopheresis (ECP), plasmapheresis, or Immunoglobulin therapy aimed at CLAD within the 28 days prior to enrollment
- •If the subject is receiving chronic Azithromycin therapy, the dose must be stable for the 28 days prior to enrollment
- •Presence of active pulmonary infection at the time of enrollment as determined by an investigator in consultation with the treating pulmonologist
- •Diagnosis of bronchial stenosis either a) requiring stenting, or b) thought to be responsible for the spirometric decline by principal investigator
- •Abnormal liver function tests (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 x upper limit of normal (ULN), Alkaline phosphatase > 2.5 x ULN, total bilirubin > ULN) or known cirrhosis (>2 times upper limit of normal of AST/ALT/AP)
- •Total white blood cell (WBC) < 3.0 K/uL
- •Moderate to Severe Renal insufficiency (CrCl <15 mL/min calculated by the Cockcroft-Gault equation)
- •Use of any medication known to cause significant interactions with pirfenidone (strong CYP1A2 inhibitors such as Fluvoxamine or Enoxacin or inducers)
- •Pregnancy or lactation. Women of child-bearing potential will have a pregnancy test at enrollment and must agree to maintain highly effective contraception with two methods of birth control from the date of consent through the end of the study.
- •Tobacco use within 6 months
- •History of alcohol abuse in the past 1 year as determined by the treating pulmonologist
- •Any condition other than CLAD that will likely result in death in the next 1 year
- •Any condition in the judgement of the principal investigator that would preclude participation in this study
- •EKG with QTc interval > 500 msec at screening
- •Listed for repeat lung transplantation
排除标准
- 未提供
研究组 & 干预措施
Pirfenidone Capsule
Method of Administration: Oral (capsule)
Dosing:
- Days 1 through 7, 267 mg three times daily;
- Days 8 through 14, 534 mg three times daily;
- Days 15 through end of treatment (24 weeks), 801 mg three times daily
干预措施: Pirfenidone Capsule (Drug)
Placebo Capsule
Method of Administration: Oral (capsule)
Dosing:
- Days 1 through 7, 267 mg three times daily;
- Days 8 through 14, 534 mg three times daily;
- Days 15 through end of treatment (24 weeks), 801 mg three times daily
干预措施: Placebo Capsule (Drug)
结局指标
主要结局
Change in Percent of Functional Small Airways Disease (fSAD) as Measured by Parametric Response Mapping
时间窗: Baseline, 24 weeks
Evaluate if pirfenidone compared to placebo will stabilize progression of fSAD by comparison of inspiratory and expiratory high resolution computed tomography (HRCT) images through co-registration to provide quantitative measures of fSAD.
次要结局
- Change in Forced Expiratory Volume 1 Over 24 Weeks (FEV1)(Baseline, 24 weeks)
- Change in Forced Vital Capacity (FVC) Over 24 Weeks(Baseline, 24 weeks)
- Number of Adverse Events Related to Study Treatment(28 weeks)
- Number of Subjects With Treatment Intolerance(24 weeks)
研究者
Vibha Lama
Henry Sewall Research Professor of Pulmonary and Critical Care Medicine and Professor of Internal Medicine, Medical School
University of Michigan