Continuation of Nintedanib After Single Lung Transplantation in IPF Subjects

NCT ID: NCT03562416

Last Updated: 2023-04-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

1 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-07-05

Study Completion Date

2021-12-21

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Idiopathic Pulmonary Fibrosis Lung Transplant; Complications

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Nintedanib

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

Group Type EXPERIMENTAL

Nintedanib

Intervention Type DRUG

Nintedanib (BIBF 1120, Ofev)

Placebo

Placebo tablet by mouth twice daily for 24 months

Group Type PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type DRUG

Placebo

Interventions

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Nintedanib

Nintedanib (BIBF 1120, Ofev)

Intervention Type DRUG

Placebo Oral Tablet

Placebo

Intervention Type DRUG

Other Intervention Names

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BIBF 1120 Ofev

Eligibility Criteria

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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
* 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
Minimum Eligible Age

35 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Boehringer Ingelheim

INDUSTRY

Sponsor Role collaborator

Temple University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jonathan A Galli, MD

Role: PRINCIPAL_INVESTIGATOR

Temple University

Locations

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Temple University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 12928646 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27772668 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25734735 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19913395 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12065382 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25745043 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25979625 (View on PubMed)

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.

Reference Type BACKGROUND

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.

Reference Type BACKGROUND
PMID: 26996931 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27863518 (View on PubMed)

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

Reference Type BACKGROUND

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.

Reference Type BACKGROUND
PMID: 28734935 (View on PubMed)

Other Identifiers

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1199-0329

Identifier Type: -

Identifier Source: org_study_id

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