NCT04271267

Brief Summary

The purpose of this investigation is to determine the association of the fraction of donor-derived cell-free DNA in plasma and lung fluid samples with acute rejection as proven by biopsy in lung transplant recipients.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
126

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Dec 2015

Longer than P75 for all trials

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 20, 2015

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 30, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 30, 2019

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

February 13, 2020

Completed
4 days until next milestone

First Posted

Study publicly available on registry

February 17, 2020

Completed
Last Updated

February 17, 2020

Status Verified

February 1, 2020

Enrollment Period

3.9 years

First QC Date

February 13, 2020

Last Update Submit

February 13, 2020

Conditions

Lung Transplant Rejection

Keywords

Lung TransplantationAcute RejectionCell-free DNA

Outcome Measures

Primary Outcomes (1)

  • Fraction dd-cfDNA, measured at the time of lung biopsy

    The fraction of dd-cfDNA in plasma and BAL fluid measured at the time of concurrent clinical lung biopsy.

    Within the first 6 months after lung transplantation

Secondary Outcomes (1)

  • Fraction dd-cfDNA, measured at the time of PFT measurement.

    Within the first 6 months after lung transplantation

Study Arms (2)

Acute Rejection Cohort

The subset of samples corresponding to biopsy-proven acute rejection

Other: No Intervention

Rejection-free Cohort

The subset of samples corresponding to a transbronchial biopsy free of acute cellular rejection.

Other: No Intervention

Interventions

No InterventionOTHER
Acute Rejection CohortRejection-free Cohort

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

CTOT-20 Study Population (Patient population for the current analyses came from within this overall population). Adult lung transplant recipients undergoing lung transplant at each of the participating centers were eligible.

You may qualify if:

  • Subject must be able to understand and provide written informed consent and
  • Must be ≥18 years of age at the time of written informed consent.
  • Anticipated listing for lung transplantation OR within 45 days of having received a single or bilateral cadaveric donor lung transplant.
  • Enrollment must occur prior to the start of bronchoscopies eligible for research bronchoalveolar lavage (BAL) sampling.
  • Undergoing first lung transplant operation.
  • Transplant surgery to be performed or performed at enrolling center. Note: Concurrent participation in immune monitoring studies or interventional device trials are permitted.

You may not qualify if:

  • Multi-organ recipient.
  • Prior recipients of any solid organ transplant, including prior lung transplant.
  • Prior or concurrent recipient of bone marrow transplant.
  • HIV infection.
  • Any condition which the investigators feel would make it unlikely for the recipient to complete follow up procedures or complete the study.
  • Participation in an investigational drug trial at the time of enrollment visit.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (11)

  • Yusen RD, Edwards LB, Dipchand AI, Goldfarb SB, Kucheryavaya AY, Levvey BJ, Lund LH, Meiser B, Rossano JW, Stehlik J; International Society for Heart and Lung Transplantation. The Registry of the International Society for Heart and Lung Transplantation: Thirty-third Adult Lung and Heart-Lung Transplant Report-2016; Focus Theme: Primary Diagnostic Indications for Transplant. J Heart Lung Transplant. 2016 Oct;35(10):1170-1184. doi: 10.1016/j.healun.2016.09.001. Epub 2016 Sep 13. No abstract available.

    PMID: 27772669BACKGROUND

  • Burton CM, Iversen M, Carlsen J, Mortensen J, Andersen CB, Steinbruchel D, Scheike T. Acute cellular rejection is a risk factor for bronchiolitis obliterans syndrome independent of post-transplant baseline FEV1. J Heart Lung Transplant. 2009 Sep;28(9):888-93. doi: 10.1016/j.healun.2009.04.022.

    PMID: 19716040BACKGROUND

  • Glanville AR, Aboyoun CL, Havryk A, Plit M, Rainer S, Malouf MA. Severity of lymphocytic bronchiolitis predicts long-term outcome after lung transplantation. Am J Respir Crit Care Med. 2008 May 1;177(9):1033-40. doi: 10.1164/rccm.200706-951OC. Epub 2008 Feb 8.

    PMID: 18263803BACKGROUND

  • Khalifah AP, Hachem RR, Chakinala MM, Yusen RD, Aloush A, Patterson GA, Mohanakumar T, Trulock EP, Walter MJ. Minimal acute rejection after lung transplantation: a risk for bronchiolitis obliterans syndrome. Am J Transplant. 2005 Aug;5(8):2022-30. doi: 10.1111/j.1600-6143.2005.00953.x.

    PMID: 15996255BACKGROUND

  • Hachem RR, Khalifah AP, Chakinala MM, Yusen RD, Aloush AA, Mohanakumar T, Patterson GA, Trulock EP, Walter MJ. The significance of a single episode of minimal acute rejection after lung transplantation. Transplantation. 2005 Nov 27;80(10):1406-13. doi: 10.1097/01.tp.0000181161.60638.fa.

    PMID: 16340783BACKGROUND

  • Stewart S, Fishbein MC, Snell GI, Berry GJ, Boehler A, Burke MM, Glanville A, Gould FK, Magro C, Marboe CC, McNeil KD, Reed EF, Reinsmoen NL, Scott JP, Studer SM, Tazelaar HD, Wallwork JL, Westall G, Zamora MR, Zeevi A, Yousem SA. Revision of the 1996 working formulation for the standardization of nomenclature in the diagnosis of lung rejection. J Heart Lung Transplant. 2007 Dec;26(12):1229-42. doi: 10.1016/j.healun.2007.10.017.

    PMID: 18096473BACKGROUND

  • Gielis EM, Ledeganck KJ, De Winter BY, Del Favero J, Bosmans JL, Claas FH, Abramowicz D, Eikmans M. Cell-Free DNA: An Upcoming Biomarker in Transplantation. Am J Transplant. 2015 Oct;15(10):2541-51. doi: 10.1111/ajt.13387. Epub 2015 Jul 16.

    PMID: 26184824BACKGROUND

  • De Vlaminck I, Valantine HA, Snyder TM, Strehl C, Cohen G, Luikart H, Neff NF, Okamoto J, Bernstein D, Weisshaar D, Quake SR, Khush KK. Circulating cell-free DNA enables noninvasive diagnosis of heart transplant rejection. Sci Transl Med. 2014 Jun 18;6(241):241ra77. doi: 10.1126/scitranslmed.3007803.

    PMID: 24944192BACKGROUND

  • De Vlaminck I, Martin L, Kertesz M, Patel K, Kowarsky M, Strehl C, Cohen G, Luikart H, Neff NF, Okamoto J, Nicolls MR, Cornfield D, Weill D, Valantine H, Khush KK, Quake SR. Noninvasive monitoring of infection and rejection after lung transplantation. Proc Natl Acad Sci U S A. 2015 Oct 27;112(43):13336-41. doi: 10.1073/pnas.1517494112. Epub 2015 Oct 12.

    PMID: 26460048BACKGROUND

  • Davis WA, Finlen Copeland CA, Todd JL, Snyder LD, Martissa JA, Palmer SM. Spirometrically significant acute rejection increases the risk for BOS and death after lung transplantation. Am J Transplant. 2012 Mar;12(3):745-52. doi: 10.1111/j.1600-6143.2011.03849.x. Epub 2011 Nov 28.

    PMID: 22123337BACKGROUND

  • Grskovic M, Hiller DJ, Eubank LA, Sninsky JJ, Christopherson C, Collins JP, Thompson K, Song M, Wang YS, Ross D, Nelles MJ, Yee JP, Wilber JC, Crespo-Leiro MG, Scott SL, Woodward RN. Validation of a Clinical-Grade Assay to Measure Donor-Derived Cell-Free DNA in Solid Organ Transplant Recipients. J Mol Diagn. 2016 Nov;18(6):890-902. doi: 10.1016/j.jmoldx.2016.07.003. Epub 2016 Oct 7.

    PMID: 27727019BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Isolated cfDNA from plasma and BAL samples

Study Officials

  • Scott Palmer, MD, MHS

    Duke University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
RETROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 13, 2020

First Posted

February 17, 2020

Study Start

December 20, 2015

Primary Completion

November 30, 2019

Study Completion

November 30, 2019

Last Updated

February 17, 2020

Record last verified: 2020-02

Data Sharing

IPD Sharing
Will not share