Impact of Pre-transplant Anti-fibrotic Therapy for IPF Upon Lung Transplant Outcomes

NCT ID: NCT04316780

Last Updated: 2021-05-20

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 320 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-04-15
• Study Completion Date: 2020-03-01

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.

Conditions

Idiopathic Pulmonary Fibrosis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Nintedanib until 0 day - 2 days before transplant

Nintedanib taken until 0 - 2 days before receiving transplant

Retrospective observational study- no intervention to occur.

Intervention Type: OTHER

Subject data will be grouped based on the anti-fibrotic medication at the time of lung transplant listing eligibility and when medication was stopped relative to the transplant.

Nintedanib until 3 days - 28 days before transplant

Nintedanib taken until 3-28 days before receiving transplant

Retrospective observational study- no intervention to occur.

Intervention Type: OTHER

Subject data will be grouped based on the anti-fibrotic medication at the time of lung transplant listing eligibility and when medication was stopped relative to the transplant.

Nintedanib until > 28 days before transplant

Nintedanib taken until more than 28 days before receiving transplant

Retrospective observational study- no intervention to occur.

Intervention Type: OTHER

Subject data will be grouped based on the anti-fibrotic medication at the time of lung transplant listing eligibility and when medication was stopped relative to the transplant.

Pirfenidone until 0 day - 1 day before transplant

Pirfenidone taken until 0 - 1 day before receiving transplant

Retrospective observational study- no intervention to occur.

Intervention Type: OTHER

Subject data will be grouped based on the anti-fibrotic medication at the time of lung transplant listing eligibility and when medication was stopped relative to the transplant.

Pirfenidone until 2 days - 28 days before transplant

Pirfenidone taken until 2-28 day before receiving transplant

Retrospective observational study- no intervention to occur.

Intervention Type: OTHER

Subject data will be grouped based on the anti-fibrotic medication at the time of lung transplant listing eligibility and when medication was stopped relative to the transplant.

Pirfenidone until > 28 days before transplant

Pirfenidone taken more than 28 days before receiving transplant

Retrospective observational study- no intervention to occur.

Intervention Type: OTHER

Subject data will be grouped based on the anti-fibrotic medication at the time of lung transplant listing eligibility and when medication was stopped relative to the transplant.

Interventions

Retrospective observational study- no intervention to occur.

Subject data will be grouped based on the anti-fibrotic medication at the time of lung transplant listing eligibility and when medication was stopped relative to the transplant.

Intervention Type: OTHER

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: collaborator

Steward St. Elizabeth's Medical Center of Boston, Inc.

OTHER

Sponsor Role: lead

Responsible Party

Peter LaCamera

Chief of Pulmonary, Critical Care and Sleep Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Peter LaCamera, M.D.

Role: PRINCIPAL_INVESTIGATOR

St. Elizabeth's Medical Center

Locations

University of Iowa

Iowa City, Iowa, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Washington University in St. Louis

St Louis, Missouri, United States

Duke University

Durham, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Temple University

Philadelphia, Pennsylvania, United States

Countries

United States

References

Astor TL, Goldberg HJ, Snyder LD, Courtwright A, Hachem R, Pena T, Zaffiri L, Criner GJ, Budev MM, Thaniyavarn T, Leonard TB, Bender S, Barakat A, Breeze JL, LaCamera P. Anti-fibrotic therapy and lung transplant outcomes in patients with idiopathic pulmonary fibrosis. Ther Adv Respir Dis. 2023 Jan-Dec;17:17534666231165912. doi: 10.1177/17534666231165912.

Reference Type: DERIVED

PMID: 37073794 (View on PubMed)

Other Identifiers

IPF-LTOS

Identifier Type: -

Identifier Source: org_study_id