CClinicalTrials.gg
Sign In
TerminatedNCT03562416Updated Apr 7, 2023

Continuation of Nintedanib After Single Lung Transplantation in IPF Subjects

A Phase 2 interventional study of Nintedanib and Placebo Oral Tablet in Idiopathic Pulmonary Fibrosis and Lung Transplant; Complications, sponsored by Temple University. Terminated at 1 site in United States. Open to participants aged 35 Years to 70 Years. Per ClinicalTrials.gov, last updated 2023-04-07.

Sponsored by Temple University · Phase 2, Interventional, and Treatment

Why this study was terminated
Low enrollment

From the registry’s dates

  • Primary completion was Dec 2021, 4 years 9 months ago, and no results have been posted to the registry.
Phase
Phase 2
Study type
Interventional
Enrollment
1
Allocation
Randomized
Ages
35 Years to 70 Years
Sex
All
01

Study summary

The aim of this study is to assess the utility of nintedanib therapy in addition to usual transplant care in single lung transplant recipients with idiopathic pulmonary fibrosis (IPF). 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.

Read the detailed description

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.

02

Conditions studied

  • Idiopathic Pulmonary Fibrosis
  • Lung Transplant; Complications
03

In context

Pulmonary Fibrosis

680 studies on the registry are indexed under Pulmonary Fibrosis; 119 are open to participants now.

This study's enrollment of 1 is below the median of 50 across 419 interventional studies indexed under Pulmonary Fibrosis.

Browse Pulmonary Fibrosis studies →

Lead sponsor

Temple University is the lead sponsor of 219 studies on the registry; 30 are open to participants now.

Of its 12 completed or terminated interventional studies of FDA-regulated products, 7 (58%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
35 Years to 70 Years
Sexes eligible
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

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

  • 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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
1 participant (actual)

Study arms

  • Experimental
    Nintedanib

    Nintedanib 150 mg tablet by mouth twice daily for 24 months.

    Drug: Nintedanib

  • Placebo comparator
    Placebo

    Placebo tablet by mouth twice daily for 24 months

    Drug: Placebo Oral Tablet

Interventions

  • DrugNintedanib

    Nintedanib (BIBF 1120, Ofev)

    Also known as: BIBF 1120, Ofev

  • DrugPlacebo Oral Tablet

    Placebo

06

What researchers measure

Primary outcomes

  1. Change in FEV1

    Change in forced expiratory volume in 1 second (FEV1)

    Time frame: Baseline to 24 months

  2. Change in FVC

    Change in forced vital capacity (FVC)

    Time frame: Baseline to 24 months

Secondary outcomes

  1. Bronchiolitis obliterans syndrome

    Incidence of bronchiolitis obliterans syndrome (BOS)

    Time frame: Baseline to 24 months

  2. Bronchial stenosis

    Incidence of surgical anastomosis bronchial stenosis

    Time frame: Baseline to 24 months

  3. Bronchial dehiscence

    Incidence of surgical anastomosis bronchial stenosis

    Time frame: Baseline to 24 months

  4. Acute cellular rejection

    Incidence of acute cellular rejection of lung allograft

    Time frame: Baseline to 24 months

  5. Drug discontinuation

    Study drug discontinuation rate due to adverse drug event

    Time frame: Baseline to 24 months

  6. Adverse drug events

    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)

    Time frame: Baseline to 24 months

  7. Vascular endothelial growth factor (VEGF) - serum

    Change in serum biomarker concentration for VEGF (pg/mL)

    Time frame: Baseline to day 30

  8. Vascular endothelial growth factor (VEGF) - BAL

    Change in BAL concentration for VEGF (pg/mL)

    Time frame: Baseline to day 30

  9. Vascular endothelial growth factor (VEGF) - serum

    Change in serum concentration for VEGF (pg/mL)

    Time frame: Baseline to day 300

  10. Vascular endothelial growth factor (VEGF) - BAL

    Change in BAL concentration for VEGF (pg/mL)

    Time frame: Baseline to day 300

  11. Fibroblast growth factor (FGF) - serum

    Change in serum concentration for FGF (pg/mL)

    Time frame: Baseline to day 30

  12. Fibroblast growth factor (FGF) - BAL

    Change in BAL concentration for FGF (pg/mL)

    Time frame: Baseline to day 30

  13. Fibroblast growth factor (FGF) - serum

    Change in serum concentration for FGF (pg/mL)

    Time frame: Baseline to day 300

  14. Fibroblast growth factor (FGF) - BAL

    Change in BAL biomarker concentration for FGF (pg/mL)

    Time frame: Baseline to day 300

  15. Platelet derived growth factor (PDGF) - serum

    Change in serum concentration for PDGF (pg/mL)

    Time frame: Baseline to day 30

  16. Platelet derived growth factor (PDGF) - BAL

    Change in BAL biomarker concentration for PDGF (pg/mL)

    Time frame: Baseline to day 30

  17. Platelet derived growth factor (PDGF) - serum

    Change in serum biomarker concentration for PDGF (pg/mL)

    Time frame: Baseline to day 300

  18. Platelet derived growth factor (PDGF) - BAL

    Change in BAL biomarker concentration for PDGF (pg/mL)

    Time frame: Baseline to day 300

  19. Peripheral blood flow cytometry - CD4 T cells

    CD4 T cell concentration in peripheral blood (cells/µL)

    Time frame: Day 30

  20. Peripheral blood flow cytometry - CD4 T cells

    CD4 T cell concentration in peripheral blood (cells/µL)

    Time frame: Day 300

  21. Peripheral blood flow cytometry - CD8 T cells

    CD8 T cell concentration in peripheral blood (cells/µL)

    Time frame: Day 30

  22. Peripheral blood flow cytometry - CD8 T cells

    CD8 T cell concentration in peripheral blood (cells/µL)

    Time frame: Day 300

  23. Peripheral blood flow cytometry - macrophages

    Macrophage concentration in peripheral blood (cells/µL)

    Time frame: Day 30

  24. Peripheral blood flow cytometry - macrophages

    Macrophage concentration in peripheral blood (cells/µL)

    Time frame: Day 300

  25. Peripheral blood flow cytometry - neutrophils

    Neutrophil concentration in peripheral blood (cells/µL)

    Time frame: Day 30

  26. Peripheral blood flow cytometry - neutrophils

    Neutrophil concentration in peripheral blood (cells/µL)

    Time frame: Day 300

  27. Survival

    Survival and time to death/cause of death (if applicable) of study subjects

    Time frame: baseline to 24 months

07

Study locations

1 site
  • Temple University Hospital
    Philadelphia, Pennsylvania 19140, United States
08

References and documents

Publications

  • Thabut G, Mal H, Castier Y, Groussard O, Brugiere O, Marrash-Chahla R, Leseche G, Fournier M. Survival benefit of lung transplantation for patients with idiopathic pulmonary fibrosis. J Thorac Cardiovasc Surg. 2003 Aug;126(2):469-75. doi: 10.1016/s0022-5223(03)00600-7. PubMed 12928646 ↗
  • Lund LH, Edwards LB, Dipchand AI, Goldfarb S, Kucheryavaya AY, Levvey BJ, Meiser B, Rossano JW, Yusen RD, Stehlik J; International Society for Heart and Lung Transplantation. The Registry of the International Society for Heart and Lung Transplantation: Thirty-third Adult Heart Transplantation Report-2016; Focus Theme: Primary Diagnostic Indications for Transplant. J Heart Lung Transplant. 2016 Oct;35(10):1158-1169. doi: 10.1016/j.healun.2016.08.017. Epub 2016 Aug 21. No abstract available. PubMed 27772668 ↗
  • Schaffer JM, Singh SK, Reitz BA, Zamanian RT, Mallidi HR. Single- vs double-lung transplantation in patients with chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis since the implementation of lung allocation based on medical need. JAMA. 2015 Mar 3;313(9):936-48. doi: 10.1001/jama.2015.1175. PubMed 25734735 ↗
  • Elicker BM, Golden JA, Ordovas KG, Leard L, Golden TR, Hays SR. Progression of native lung fibrosis in lung transplant recipients with idiopathic pulmonary fibrosis. Respir Med. 2010 Mar;104(3):426-33. doi: 10.1016/j.rmed.2009.10.019. Epub 2009 Nov 12. PubMed 19913395 ↗
  • Wahidi MM, Ravenel J, Palmer SM, McAdams HP. Progression of idiopathic pulmonary fibrosis in native lungs after single lung transplantation. Chest. 2002 Jun;121(6):2072-6. doi: 10.1378/chest.121.6.2072. PubMed 12065382 ↗
  • Wollin L, Wex E, Pautsch A, Schnapp G, Hostettler KE, Stowasser S, Kolb M. Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis. Eur Respir J. 2015 May;45(5):1434-45. doi: 10.1183/09031936.00174914. Epub 2015 Mar 5. PubMed 25745043 ↗
  • Xu Z, Ramachandran S, Gunasekaran M, Zhou F, Trulock E, Kreisel D, Hachem R, Mohanakumar T. MicroRNA-144 dysregulates the transforming growth factor-beta signaling cascade and contributes to the development of bronchiolitis obliterans syndrome after human lung transplantation. J Heart Lung Transplant. 2015 Sep;34(9):1154-62. doi: 10.1016/j.healun.2015.03.021. Epub 2015 Mar 27. PubMed 25979625 ↗
  • Sjoland AA, Callerfelt AK, Thiman L, et al. Prostacyclin and VEGF in the rejection process after lung transplantation-A possible biomarker [abstract]. Eur Respir J. 2016; PA4040.
  • Suhling H, Bollmann B, Gottlieb J. Nintedanib in restrictive chronic lung allograft dysfunction after lung transplantation. J Heart Lung Transplant. 2016 Jul;35(7):939-40. doi: 10.1016/j.healun.2016.01.1220. Epub 2016 Feb 9. No abstract available. PubMed 26996931 ↗
  • Delanote I, Wuyts WA, Yserbyt J, Verbeken EK, Verleden GM, Vos R. Safety and efficacy of bridging to lung transplantation with antifibrotic drugs in idiopathic pulmonary fibrosis: a case series. BMC Pulm Med. 2016 Nov 18;16(1):156. doi: 10.1186/s12890-016-0308-z. PubMed 27863518 ↗
  • Dorey-Stein Z, Galli JA, Criner GJ. Effect of antifibrotic therapy in patients with idiopathic pulmonary fibrosis awaiting lung transplantation [abstract]. Am J Respir Crit Care Med. 2017;195:A5386
  • Leuschner G, Stocker F, Veit T, Kneidinger N, Winter H, Schramm R, Weig T, Matthes S, Ceelen F, Arnold P, Munker D, Klenner F, Hatz R, Frankenberger M, Behr J, Neurohr C. Outcome of lung transplantation in idiopathic pulmonary fibrosis with previous anti-fibrotic therapy. J Heart Lung Transplant. 2017 Jul 5:S1053-2498(17)31886-7. doi: 10.1016/j.healun.2017.07.002. Online ahead of print. PubMed 28734935 ↗

Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 7, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03562416
Lead sponsor
Temple University
Collaborators
Boehringer Ingelheim
Responsible party
Sponsor
First posted
Jun 19, 2018
Start date
Jul 5, 2019
Primary completion
Dec 21, 2021
Completion
Dec 21, 2021
Last update
Apr 7, 2023

Study contacts

Jonathan A Galli, MD
principal investigator · Temple University

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in Apr 2023. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Pulmonary Fibrosis→

Other studies from this sponsor

Temple University

Start the discussion