Continuation of Nintedanib After Single Lung Transplantation in IPF Subjects
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ClinicalTrials.gov Identifier: NCT03562416 |
Recruitment Status : Unknown
Verified July 2019 by Temple University.
Recruitment status was: Recruiting
First Posted : June 19, 2018
Last Update Posted : July 10, 2019
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Condition or disease | Intervention/treatment | Phase |
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Idiopathic Pulmonary Fibrosis Lung Transplant; Complications | Drug: Nintedanib Drug: Placebo Oral Tablet | Phase 2 |
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.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 20 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | 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 |
Actual Study Start Date : | July 5, 2019 |
Estimated Primary Completion Date : | December 2021 |
Estimated Study Completion Date : | December 2021 |

Arm | Intervention/treatment |
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Experimental: Nintedanib
Nintedanib 150 mg tablet by mouth twice daily for 24 months.
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Drug: Nintedanib
Nintedanib (BIBF 1120, Ofev)
Other Names:
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Placebo Comparator: Placebo
Placebo tablet by mouth twice daily for 24 months
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Drug: Placebo Oral Tablet
Placebo |
- Change in FEV1 [ Time Frame: Baseline to 24 months ]Change in forced expiratory volume in 1 second (FEV1)
- Change in FVC [ Time Frame: Baseline to 24 months ]Change in forced vital capacity (FVC)
- Bronchiolitis obliterans syndrome [ Time Frame: Baseline to 24 months ]Incidence of bronchiolitis obliterans syndrome (BOS)
- Bronchial stenosis [ Time Frame: Baseline to 24 months ]Incidence of surgical anastomosis bronchial stenosis
- Bronchial dehiscence [ Time Frame: Baseline to 24 months ]Incidence of surgical anastomosis bronchial stenosis
- Acute cellular rejection [ Time Frame: Baseline to 24 months ]Incidence of acute cellular rejection of lung allograft
- Drug discontinuation [ Time Frame: Baseline to 24 months ]Study drug discontinuation rate due to adverse drug event
- Adverse drug events [ Time Frame: Baseline to 24 months ]Incidence of adverse drug events (i.e. elevation of liver transaminases greater than 3 times the upper limit of normal, diarrhea, nausea, vomiting, anorexia, GERD)
- Vascular endothelial growth factor (VEGF) - serum [ Time Frame: Baseline to day 30 ]Change in serum biomarker concentration for VEGF (pg/mL)
- Vascular endothelial growth factor (VEGF) - BAL [ Time Frame: Baseline to day 30 ]Change in BAL concentration for VEGF (pg/mL)
- Vascular endothelial growth factor (VEGF) - serum [ Time Frame: Baseline to day 300 ]Change in serum concentration for VEGF (pg/mL)
- Vascular endothelial growth factor (VEGF) - BAL [ Time Frame: Baseline to day 300 ]Change in BAL concentration for VEGF (pg/mL)
- Fibroblast growth factor (FGF) - serum [ Time Frame: Baseline to day 30 ]Change in serum concentration for FGF (pg/mL)
- Fibroblast growth factor (FGF) - BAL [ Time Frame: Baseline to day 30 ]Change in BAL concentration for FGF (pg/mL)
- Fibroblast growth factor (FGF) - serum [ Time Frame: Baseline to day 300 ]Change in serum concentration for FGF (pg/mL)
- Fibroblast growth factor (FGF) - BAL [ Time Frame: Baseline to day 300 ]Change in BAL biomarker concentration for FGF (pg/mL)
- Platelet derived growth factor (PDGF) - serum [ Time Frame: Baseline to day 30 ]Change in serum concentration for PDGF (pg/mL)
- Platelet derived growth factor (PDGF) - BAL [ Time Frame: Baseline to day 30 ]Change in BAL biomarker concentration for PDGF (pg/mL)
- Platelet derived growth factor (PDGF) - serum [ Time Frame: Baseline to day 300 ]Change in serum biomarker concentration for PDGF (pg/mL)
- Platelet derived growth factor (PDGF) - BAL [ Time Frame: Baseline to day 300 ]Change in BAL biomarker concentration for PDGF (pg/mL)
- Peripheral blood flow cytometry - CD4 T cells [ Time Frame: Day 30 ]CD4 T cell concentration in peripheral blood (cells/µL)
- Peripheral blood flow cytometry - CD4 T cells [ Time Frame: Day 300 ]CD4 T cell concentration in peripheral blood (cells/µL)
- Peripheral blood flow cytometry - CD8 T cells [ Time Frame: Day 30 ]CD8 T cell concentration in peripheral blood (cells/µL)
- Peripheral blood flow cytometry - CD8 T cells [ Time Frame: Day 300 ]CD8 T cell concentration in peripheral blood (cells/µL)
- Peripheral blood flow cytometry - macrophages [ Time Frame: Day 30 ]Macrophage concentration in peripheral blood (cells/µL)
- Peripheral blood flow cytometry - macrophages [ Time Frame: Day 300 ]Macrophage concentration in peripheral blood (cells/µL)
- Peripheral blood flow cytometry - neutrophils [ Time Frame: Day 30 ]Neutrophil concentration in peripheral blood (cells/µL)
- Peripheral blood flow cytometry - neutrophils [ Time Frame: Day 300 ]Neutrophil concentration in peripheral blood (cells/µL)
- Survival [ Time Frame: baseline to 24 months ]Survival and time to death/cause of death (if applicable) of study subjects

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Ages Eligible for Study: | 35 Years to 70 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Adults between the ages of 35-70.
- Lung transplantation listing diagnosis of pulmonary fibrosis
- Recipient of single lung transplantation within the past 60 days
Exclusion Criteria:
- 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
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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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03562416
Contact: Francine McGonagle, BSN, RN | 215-707-2682 | Francine.McGonagle@tuhs.temple.edu | |
Contact: Shubhra Srivastava-Malhotra | 215-707-0945 | Shubhra.Srivastava-Malhotra@tuhs.temple.edu |
United States, Pennsylvania | |
Temple University Hospital | Recruiting |
Philadelphia, Pennsylvania, United States, 19140 | |
Contact: Francine McGonagle, BSN,RN 215-707-2682 Francine.McGonagle@tuhs.temple.edu | |
Contact: Shubhra Srivastava-Malhotra 215-707-0945 Shubhra.Srivastava-Malhotra@tuhs.temple.edu | |
Principal Investigator: Jonathan A Galli, MD | |
Sub-Investigator: Gerard J Criner, MD | |
Sub-Investigator: Patrick Mulhall, MD | |
Sub-Investigator: Kartik Shenoy, MD | |
Sub-Investigator: James Brown, MD | |
Sub-Investigator: Thomas Rogers, PhD |
Principal Investigator: | Jonathan A Galli, MD | Temple University |
Responsible Party: | Temple University |
ClinicalTrials.gov Identifier: | NCT03562416 |
Other Study ID Numbers: |
1199-0329 |
First Posted: | June 19, 2018 Key Record Dates |
Last Update Posted: | July 10, 2019 |
Last Verified: | July 2019 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Pulmonary Fibrosis Idiopathic Pulmonary Fibrosis Fibrosis Pathologic Processes Lung Diseases Respiratory Tract Diseases |
Nintedanib Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |