Idiopathic Pulmonary FibrosisIPF-LTOSNCT04316780
Impact of Pre-transplant Anti-fibrotic Therapy for IPF Upon Lung Transplant Outcomes
An observational study of Idiopathic Pulmonary Fibrosis, run by Steward St. Elizabeth's Medical Center of Boston, Inc. at 8 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Idiopathic Pulmonary Fibrosis
- How many people
- 320 participants
- Where
- 8 sitesUnited States
- Study dates
- 15 Apr 2019to 1 Mar 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 1. Patients that underwent additional interventions (i.e. coronary artery bypass grafting, valve replacement) at the time of their lung transplant
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Cleveland Clinic
Cleveland, Ohio, 44195
Duke University
Durham, North Carolina, 27705
University of Iowa
Iowa City, Iowa, 52242
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Temple University
Philadelphia, Pennsylvania, 19122
Washington University in St. Louis
St Louis, Missouri, 63110
About this study
Official title: Impact of Pre-transplant Anti-fibrotic Therapy for Idiopathic Pulmonary Fibrosis Upon Lung Transplant Outcomes
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.
Read the 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:
- 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:
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
- Being tested
- Retrospective observational study- no intervention to occur.
- Keywords
- Lung Transplant, Nintedanib, Pirfenidone, IPF
- Medical subject headings
- Idiopathic Pulmonary Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Retrospective observational study- no intervention to occur.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.
| Study group | Role | What they receive |
|---|---|---|
| Nintedanib until 0 day - 2 days before transplant | Nintedanib taken until 0 - 2 days before receiving transplant Receives: Other: Retrospective observational study- no intervention to occur. | |
| Nintedanib until 3 days - 28 days before transplant | Nintedanib taken until 3-28 days before receiving transplant Receives: Other: Retrospective observational study- no intervention to occur. | |
| Nintedanib until > 28 days before transplant | Nintedanib taken until more than 28 days before receiving transplant Receives: Other: Retrospective observational study- no intervention to occur. | |
| Pirfenidone until 0 day - 1 day before transplant | Pirfenidone taken until 0 - 1 day before receiving transplant Receives: Other: Retrospective observational study- no intervention to occur. | |
| Pirfenidone until 2 days - 28 days before transplant | Pirfenidone taken until 2-28 day before receiving transplant Receives: Other: Retrospective observational study- no intervention to occur. | |
| Pirfenidone until > 28 days before transplant | Pirfenidone taken more than 28 days before receiving transplant Receives: Other: Retrospective observational study- no intervention to occur. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lung transplant complications
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.
Measured: 6 months
Short term survival
Post-transplant, patients will be followed for six months to estimate the mean, median, and variability of short-term survival in each group.
Measured: 6 months
Patient deaths while awaiting a transplant
The proportion of patients in each of the six groups who die after being listed and prior to receiving a transplant.
Measured: From date of listed for transplant until the date of death from any cause assessed up to 54 months.
Disease progression while awaiting a transplant
Changes in forced vital capacity (FVC) as measured in liters will be compared between groups.
Measured: From date of listed for transplant until the date of transplant or date of death from any cause assessed up to 54 months.
Disease progression while awaiting a transplant
Changes in percent predicted forced vital capacity (FVC%) as measured in percentage will be compared between groups.
Measured: From date of listed for transplant until the date of transplant or date of death from any cause assessed up to 54 months.
Disease progression while awaiting a transplant
Changes in diffusing capacity of the lung for carbon monoxide (DLCO) as measured in ml/mmHg/min will be compared between groups.
Measured: From date of listed for transplant until the date of transplant or date of death from any cause assessed up to 54 months.
Disease progression while awaiting a transplant
Changes in percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) as measured in percentage will be compared between groups.
Measured: From date of listed for transplant until the date of transplant or date of death from any cause assessed up to 54 months.
Disease progression while awaiting a transplant
Changes in Lung Allocation Score (scale from 0-100; higher score reflecting higher priority for transplant) will be compared between groups.
Measured: From date of listed for transplant until the date of transplant or date of death from any cause assessed up to 54 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2020
- Study start15 Apr 2019
- Primary completion31 Dec 2019
- Study completion1 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Idiopathic Pulmonary FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 320 participants (actual)
Sponsor and investigators
- Lead sponsor
- Steward St. Elizabeth's Medical Center of Boston, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- Boehringer Ingelheim
- Responsible party
- Principal investigator, Peter LaCamera, Steward St. Elizabeth's Medical Center of Boston, Inc.
- Investigators
- Peter LaCamera, M.D., Principal investigator, St. Elizabeth's Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04316780
- Sponsor's protocol ID
- IPF-LTOS
- Acronym
- IPF-LTOS
- Status last verified
- May 2021
- First submitted
- 18 Apr 2019
- Last updated
- 20 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 37073794
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Pre-transplant Anti-fibrotic Therapy for Idiopathic Pulmonary Fibrosis Upon Lung Transplant Outcomes
- ClinicalTrials.gov ID
- NCT04316780
- Acronym / sponsor ID
- IPF-LTOS / IPF-LTOS
- Conditions
- Idiopathic Pulmonary Fibrosis
- Keywords
- Lung Transplant, Nintedanib, Pirfenidone, IPF
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 320 participants (actual)
- Lead sponsor
- Steward St. Elizabeth's Medical Center of Boston, Inc.University, hospital or other
- Collaborators
- Boehringer Ingelheim
- Study start
- 15 Apr 2019 (actual)
- Primary completion
- 31 Dec 2019 (actual)
- Study completion
- 1 Mar 2020 (actual)
- First posted
- 20 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Nintedanib until 0 day - 2 days before transplant | – | Other: Retrospective observational study- no intervention to occur.Nintedanib taken until 0 - 2 days before receiving transplant |
| Nintedanib until 3 days - 28 days before transplant | – | Other: Retrospective observational study- no intervention to occur.Nintedanib taken until 3-28 days before receiving transplant |
| Nintedanib until > 28 days before transplant | – | Other: Retrospective observational study- no intervention to occur.Nintedanib taken until more than 28 days before receiving transplant |
| Pirfenidone until 0 day - 1 day before transplant | – | Other: Retrospective observational study- no intervention to occur.Pirfenidone taken until 0 - 1 day before receiving transplant |
| Pirfenidone until 2 days - 28 days before transplant | – | Other: Retrospective observational study- no intervention to occur.Pirfenidone taken until 2-28 day before receiving transplant |
| Pirfenidone until > 28 days before transplant | – | Other: Retrospective observational study- no intervention to occur.Pirfenidone taken more than 28 days before receiving transplant |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (1 listed)
- 1. Patients that underwent additional interventions (i.e. coronary artery bypass grafting, valve replacement) at the time of their lung transplant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Other | Nintedanib until 0 day - 2 days before transplant, Nintedanib until 3 days - 28 days before transplant, Nintedanib until > 28 days before transplant, Pirfenidone until 0 day - 1 day before transplant, Pirfenidone until 2 days - 28 days before transplant, Pirfenidone until > 28 days before transplant |
Primary outcome
Lung transplant complications
Time frame: 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.
Short term survival
Time frame: 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.
Patient deaths while awaiting a transplant
Time frame: 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.
Disease progression while awaiting a transplant
Time frame: 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 forced vital capacity (FVC) as measured in liters will be compared between groups.
Disease progression while awaiting a transplant
Time frame: 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 percent predicted forced vital capacity (FVC%) as measured in percentage will be compared between groups.
Disease progression while awaiting a transplant
Time frame: 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 diffusing capacity of the lung for carbon monoxide (DLCO) as measured in ml/mmHg/min will be compared between groups.
Disease progression while awaiting a transplant
Time frame: 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 percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) as measured in percentage will be compared between groups.
Disease progression while awaiting a transplant
Time frame: 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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2021.
- Derived from this study: PubMed 37073794Astor 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter LaCamera, M.D. principal investigator
St. Elizabeth's Medical Center
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Idiopathic Pulmonary Fibrosis, run by Steward St. Elizabeth's Medical Center of Boston, Inc. at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Lung transplant complications (time frame: 6 months). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04316780, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2021.