Clinical trial NCT04316780: Impact of Pre-transplant Anti-fibrotic Therapy for IPF Upon Lung Transplant Outcomes
Official title: Impact of Pre-transplant Anti-fibrotic Therapy for Idiopathic Pulmonary Fibrosis Upon Lung Transplant Outcomes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: Lung Transplant
Nintedanib
Pirfenidone
IPF
Lead sponsor: Steward St. Elizabeth's Medical Center of Boston, Inc.
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
First posted: 2020-03-20
Enrollment: 320
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with IPF listed for lung transplantation who were being treated with one of the 2 anti-fibrotic therapies continuously for at least 90 days at the time of their eligibility for listing will be included.

Brief summary: 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.

Detailed description: 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:

1. Does stopping the medications prematurely while awaiting lung transplantation result in a greater risk of death due to acceleration of IPF?
2. Does continuing the medications until the time of transplant increase the risk of intra- and/or post-operative complications?
3. 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:

Aim 1: Assess whether the time period between discontinuation of anti-fibrotic therapy for IPF and lung transplantation impacts (a) the risk of intra-operative and post-transplant complications and (b) short term survival.

Aim 2: Explore whether discontinuing anti-fibrotic therapy prior to lung transplantation is associated with increased risk of death while awaiting a transplant.

At the participating sites, all patients with IPF listed for lung transplantation who were being treated with one of the 2 anti-fibrotic therapies continuously for at least 90 days at the time of their eligibility for listing will be included. Outcomes include events that occurred after being listed and while waiting for lung transplantation, intra-operative and peri-operative events, and mortality data out to 6 months. Patients that underwent additional interventions (coronary artery bypass grafting, valve replacement) at the time of their transplant will be excluded.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of IPF
2. Taking one of the two anti-fibrotic therapies (nintedanib or pirfenidone) continuously for at least 90 days at the time of eligibility for listing
3. Listed for lung transplantation between July 1, 2015 and June 30, 2019

Exclusion Criteria:

1. Patients that underwent additional interventions (i.e. coronary artery bypass grafting, valve replacement) at the time of their lung transplant

Primary outcomes:
measure: Lung transplant complications
timeFrame: 6 months
measure: Short term survival
timeFrame: 6 months
measure: Patient deaths while awaiting a transplant
timeFrame: From date of listed for transplant until the date of death from any cause assessed up to 54 months.
measure: Disease progression while awaiting a transplant
timeFrame: From date of listed for transplant until the date of transplant or date of death from any cause assessed up to 54 months.
measure: Disease progression while awaiting a transplant
timeFrame: From date of listed for transplant until the date of transplant or date of death from any cause assessed up to 54 months.
measure: Disease progression while awaiting a transplant
timeFrame: From date of listed for transplant until the date of transplant or date of death from any cause assessed up to 54 months.
measure: Disease progression while awaiting a transplant
timeFrame: From date of listed for transplant until the date of transplant or date of death from any cause assessed up to 54 months.
measure: Disease progression while awaiting a transplant
timeFrame: From date of listed for transplant until the date of transplant or date of death from any cause assessed up to 54 months.
Secondary outcomes:
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
Study officials:
affiliation: St. Elizabeth's Medical Center
name: Peter LaCamera, M.D.
role: PRINCIPAL_INVESTIGATOR
References: