Nintedanib Plus Usual Transplant Care Compared to Usual Transplant Care Alone After Single Lung Transplantation in Patients With Idiopathic Pulmonary Fibrosis: a Pilot Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Change in FVC
研究概览
简要总结
The aim of this study is to assess the utility of nintedanib therapy in addition to usual transplant care in single lung transplant recipients with idiopathic pulmonary fibrosis (IPF). The investigators hypothesize that in IPF subjects who undergo single lung transplantation the administration of nintedanib 150 mg twice daily in addition to usual transplant care will result in better preservation of lung function at 24 months.
详细描述
Lung transplantation is the only treatment option that augments survival in patients with idiopathic pulmonary fibrosis (IPF). Despite several advancements in lung transplantation over the past three decades, long-term survival rates have remained low compared to other solid organ transplantations. The median survival after lung transplantation is only 5.8 years. Multiple factors account for the relatively low survival post-transplant, but chronic rejection resulting in obliterative bronchiolitis is a predominate cause. Further research is needed to develop medical therapeutic interventions that improve survival in IPF patients who undergo only single lung transplantation.
Nintedanib, a novel tyrosine kinase inhibitor, exhibits antifibrotic properties via multiple mechanisms including the inhibition of the receptor tyrosine kinases platelet derived growth factor (PDGF) receptor, fibroblast growth factor (FGF) receptor, and vascular endothelial growth factor (VEGF) receptor. Several mediators of pulmonary fibrosis including VEGF, FGF, and transforming growth factor beta (TGF-β) have also been implicated in the pathogenesis of bronchiolitis obliterans syndrome (BOS), the most common type of chronic lung allograft rejection.
Nintedanib is safe to continue until the time of lung transplantation and has not been shown to worsen perioperative outcomes in small case series, single center cohorts and our center's personal experience. The current practice in lung transplant medicine is to discontinue antifibrotic therapy after lung transplantation in IPF. In IPF patients who undergo single lung transplant, nintedanib therapy has the potential to preserve lung function in both the native fibrotic lung and the new lung allograft.
The investigators propose a randomized and placebo-controlled single center pilot trial comparing nintedanib therapy plus usual care to usual care only in IPF patients after single lung transplant. The investigators hypothesize that in IPF subjects who undergo single lung transplantation the administration of nintedanib 150 mg twice daily in addition to usual transplant care will result in better preservation of lung function at 24 months.
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
- 35 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults between the ages of 35-
- •Lung transplantation listing diagnosis of pulmonary fibrosis
- •Recipient of single lung transplantation within the past 60 days
排除标准
- •History of intolerability to nintedanib (i.e. discontinued nintedanib in the pre-transplant period due to adverse drug effects)
- •Liver transaminase elevation (AST or ALT > 1.5X the upper limit of normal)
- •Total bilirubin > 1.5X the upper limit of normal
- •Drugs that interfere with the metabolism or elimination of nintedanib or its metabolites - St. John's wort, carbamazepine, phenytoin, rifampin, dexamethasone, and others.
- •Any history of bronchial anastomosis dehiscence or stenosis
- •Bleeding risk, defined as any of the following:
- •Full-dose therapeutic anticoagulation (i.e. vitamin K antagonist, direct thrombin inhibitors, etc.)
- •History of hemorrhagic central nervous system (CNS) event within 12 months of enrollment
- •Coagulation parameters: international normalized ratio (INR) > 2, prolongation of prothrombin time (PT) and partial thromboplastin time (PTT) by > 1.5X the upper limit of normal at enrollment
研究组 & 干预措施
Nintedanib
Nintedanib 150 mg tablet by mouth twice daily for 24 months.
干预措施: Nintedanib (Drug)
Placebo
Placebo tablet by mouth twice daily for 24 months
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
Change in FVC
时间窗: Baseline to 24 months
Change in forced vital capacity (FVC)
Change in FEV1
时间窗: Baseline to 24 months
Change in forced expiratory volume in 1 second (FEV1)
次要结局
- Bronchial stenosis(Baseline to 24 months)
- Peripheral blood flow cytometry - CD8 T cells(Day 300)
- Bronchiolitis obliterans syndrome(Baseline to 24 months)
- Vascular endothelial growth factor (VEGF) - serum(Baseline to day 300)
- Drug discontinuation(Baseline to 24 months)
- Fibroblast growth factor (FGF) - BAL(Baseline to day 300)
- Peripheral blood flow cytometry - macrophages(Day 300)
- Adverse drug events(Baseline to 24 months)
- Fibroblast growth factor (FGF) - serum(Baseline to day 300)
- Peripheral blood flow cytometry - CD4 T cells(Day 300)
- Platelet derived growth factor (PDGF) - serum(Baseline to day 300)
- Platelet derived growth factor (PDGF) - BAL(Baseline to day 300)
- Peripheral blood flow cytometry - neutrophils(Day 300)
- Bronchial dehiscence(Baseline to 24 months)
- Acute cellular rejection(Baseline to 24 months)
- Vascular endothelial growth factor (VEGF) - BAL(Baseline to day 300)
- Survival(baseline to 24 months)