Impact of Pre-transplant Anti-fibrotic Therapy for Idiopathic Pulmonary Fibrosis Upon Lung Transplant Outcomes
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 320
- 试验地点
- 8
- 主要终点
- Disease progression while awaiting a transplant
研究概览
简要总结
Two oral medications, nintedanib and pirfenidone, were approved simultaneously by the FDA in October 2014 for the treatment of this disease. They are both considered anti-fibrotic agents and they each proved to slow the progression of disease in their respective clinical trials. Because of their anti-fibrotic properties, there have been concerns about the potential of these medications to impair wound healing following surgery. These concerns have led to variable approaches with respect to the management of the medications in patients listed for lung transplantation.
It is unknown whether continuing anti-fibrotic medications until the time of transplant increases the risks of intra-operative and post-transplant complications. Conversely, there are concerns that stopping the medications prematurely may promote a more rapid clinical decline in those awaiting transplantation and increase risk of death while on waiting lists. Whether there is a risk or benefit of continuing the medications during the pre-transplant period deserves investigation with the goal of establishing guidelines and best-practices. Once more is known about how best to manage anti-fibrotic therapy in the pre-transplant period, the question of whether these medications should be restarted following transplantation will also ultimately deserve exploration.
详细描述
Idiopathic pulmonary fibrosis (IPF) is a terminal illness that typically develops in the sixth and seventh decades of life. It is a relentless fibrotic parenchymal lung disease that results in restrictive physiology and worsening symptoms of cough and shortness of breath. The median life expectancy from the time of diagnosis is in the 3-5 year range. The only therapy that has proven to extend life expectancy is lung transplantation.
There are 3 relevant, unanswered questions pertaining to the use of anti-fibrotic therapy for IPF around the time of lung transplantation:
- Does stopping the medications prematurely while awaiting lung transplantation result in a greater risk of death due to acceleration of IPF?
- Does continuing the medications until the time of transplant increase the risk of intra- and/or post-operative complications?
- Is there a role for post-transplant anti-fibrotic therapy to reduce complications such as stenosis of the anastomosis, bronchiolitis obliterans syndrome and restrictive allograft syndrome, and/or to preserve native lung function following a single lung transplant?
The primary goal of this observational, pilot study is to collect retrospective data with the intention of using the findings to select primary outcomes and determine sample size for a sufficiently powered subsequent study.
The investigators will focus on the following aims:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of IPF
- •Taking one of the two anti-fibrotic therapies (nintedanib or pirfenidone) continuously for at least 90 days at the time of eligibility for listing
- •Listed for lung transplantation between July 1, 2015 and June 30, 2019
排除标准
- •Patients that underwent additional interventions (i.e. coronary artery bypass grafting, valve replacement) at the time of their lung transplant
结局指标
主要结局
Disease progression while awaiting a transplant
时间窗: From date of listed for transplant until the date of transplant or date of death from any cause assessed up to 54 months.
Changes in Lung Allocation Score (scale from 0-100; higher score reflecting higher priority for transplant) will be compared between groups.
Lung transplant complications
时间窗: 6 months
The proportions of patients in each group who develop (a) intra-operative outcomes and complications (need for ECMO/cardiopulmonary bypass and blood transfusions) and (b) post-transplant outcomes and complications (mechanical ventilation days, number of days with air leak and chest tube, primary graft dysfunction, anastomotic dehiscence, wound dehiscence, sternal breakdown / dehiscence, post-op infection, post-operative return to OR, blood transfusions) will be calculated.
Patient deaths while awaiting a transplant
时间窗: From date of listed for transplant until the date of death from any cause assessed up to 54 months.
The proportion of patients in each of the six groups who die after being listed and prior to receiving a transplant.
Short term survival
时间窗: 6 months
Post-transplant, patients will be followed for six months to estimate the mean, median, and variability of short-term survival in each group.
次要结局
未报告次要终点
研究者
Peter LaCamera
Chief of Pulmonary, Critical Care and Sleep Medicine
Steward St. Elizabeth's Medical Center of Boston, Inc.