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Lung TransplantationNCT05837663

Trifecta-Lung cfDNA-MMDx Study

An observational study of Lung Transplantation, run by University of Alberta at 19 sites in 5 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Demonstrate the relationship between dd-cfDNA levels and HLA antibodies in blood transplant recipient and Demonstrate the Molecular Microscope® (MMDx) Diagnostic System results in indication and protocol biopsies from lung transplants. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lung Transplantation
How many people
600 participants
Where
19 sitesin 5 countries
Study dates
1 Nov 2023to Dec 2028
Phase
Observational
Are there results?
Not yet: the study is under way

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 18 years and older
  • All sexes
  • Adult, Older adult

Study population: All adult lung transplant recipients undergoing indication biopsy for suspected graft dysfunction will be eligible.

Who may be able to join

  • Adult, Older adult

Who cannot join

  • Patients will be excluded from the study if they decline participation Are unable to give informed consent. Recipients of multiple organs, cancer patients and pregnant women

Trial locations and contacts

19 sites in 5 countries. Contact the study team or a site near you to ask about taking part.

Konrad S Famulski, PhD DSc contact

1 780 782 9463

konrad@ualberta.ca

Robert Polakowski, PhD contact

1 780 492 5091

polakows@ualberta.ca

19 sites in 5 countries

United States12 sites, 12 recruiting

  • Johns Hopkins Interventional Pulmonology, Sheikh Zayed Tower, Room 7125L, 1800 Orleans Street

    Baltimore, Maryland, 21287

    Cheryl Pai, cpai3@jhu.edu

    Jeffrey Thiboutot, MD MHS

    Recruiting

  • The Ohio State University Wexner Medical Center, 410 W 10th Ave

    Columbus, Ohio, 43210

    Erwin Cooper, Cooper.Erwin@osumc.edu

    Justin Rosenheck, DO

    Recruiting

  • BAYLOR SCOTT & WHITE RESEARCH INSTITUTE , 3409 Worth Street

    Dallas, Texas, 75246

    Felicia Padilla, 214-820-1771, Felicia.Padilla@bswhealth.org

    Todd Grazia, MD

    Recruiting

  • UT Southwestern Medical Center, 5939 Harry Hines Blvd.

    Dallas, Texas, 75390

    Irina L Timofte, MD, Irina.Timofte@UTSouthwestern.edu

    Irina L Timofte, MD

    Recruiting

  • Division of Pulmonary, Critical Care and Sleep Medicine, University of Florida, College of Medicine

    Gainesville, Florida, 32610

    Duncan Lewis, BS, CCRP, Duncan.Lewis@medicine.ufl.edu

    Amir Emtiazjoo, MD, MSc

    Recruiting

  • Houston Methodist Lung Transplant Center, 6550 Fannin St., SM1001

    Houston, Texas, 77030

    Darrel W Cleere, DWCLEERE@houstonmethodist.org

    Howard J Huang, MD

    Recruiting

  • Indiana University Methodist Hospital 1812 N. Capitol Ave Suite W131L

    Indianapolis, Indiana, 46202

    Erin Sartoris, RN, esartoris@iuhealth.org

    Nikki Smith, MD

    Recruiting

  • Mayo Clinic Florida, 4500 San Pablo Rd

    Jacksonville, Florida, 32224

    Stacey N Caster, Caster.Stacey@mayo.edu

    Remzi Bag, MD

    Recruiting

  • Division of Pulmonary, Allergy & Critical Care Medicine Columbia University Irving Medical Center

    New York, New York, 10032

    Shreena Patel, MPH, LPN, sp3646@cumc.columbia.edu

    Kemarut Laothmatas, MD

    Recruiting

  • St. Joseph's Hospital and Medical Center 350 West Thomas Road, Floor 8HLT

    Phoenix, Arizona, 85013

    Chanti F Smith, chanti.smith@dignityhealth.org

    Rajat Walia, MD

    Recruiting

  • UT Health San Antonio 7703 Floyd Curl Drive, MSC: 7858

    San Antonio, Texas, 78229

    Renee Walruff, BS, walruff@uthscsa.edu

    Lara Jones, DO

    Recruiting

  • USF Health, Morsani College of Medicine, 12901 Bruce B. Downs Blvd. MDC40

    Tampa, Florida, 33612

    Jennifer Olvedy, jolvedy@tgh.org

    Satish Chandrashekaran, MD

    Not yet recruiting

Other trials in United States

Canada3 sites, 3 recruiting

  • Department of Medicine, University of Alberta

    Edmonton, Alberta, T6G 2G3

    Kieran Halloran, MD MSC, 1 780 492 2691, kieran.halloran@ualberta.ca

    Kieran Halloran, MD MSc

    Recruiting

  • Alberta Transplant Applied Genomics Centre, University of Alberta

    Edmonton, Alberta, T^g 2E1

    Konrad S Famulski, PhD DSc, 1 7807829463, konrad@ualberta.ca

    Robert Polakowski, PhD, 1 7804925091, polakows@ualberta.ca

    Recruiting

  • University Health Network, Toronto General Hospital

    Toronto, Ontario, M5G 2C4

    Shaf Keshavjee, MD MSc, 1 416-340-3863, shaf.keshavjee@uhn.ca

    Shaf Keshavjee, MD MSc

    Recruiting

Other trials in Canada

Czechia2 sites, 2 recruiting

  • Motol University Hospital, V Uvalu 84

    Prague, 15006

    Jolana Hertova, +420 775 216 790, jolana.hertova@fnmotol.cz

    Jan Havlin, MD

    Recruiting

  • Charles University/Hospital Motol

    Prague

    Jan Havlin, MD, havlin.jan@gmail.com

    Jan Havlin, MD

    Recruiting

Other trials in Czechia

Australia1 site, 1 recruiting

  • The Alfred Hospital, Monash University

    Melbourne

    Glen Westall, MD PhD, +61 3 9076 2405, g.westall@alfred.org.au

    Glen Westall, MD PhD

    Recruiting

Other trials in Australia

Austria1 site, 1 recruiting

  • Department of Thoracic Surgery, Medical University of Vienna

    Vienna

    Dagmar Liebhart, dagmar.liebhart@meduniwien.ac.at

    Konrad Hoetzenecker, Professor

    Not yet recruiting

Other trials in Austria

About this study

Official title: Trifecta-Lung cfDNA-MMDx Study: Comparing the Dd-cfDNA Test to MMDx Microarray Test and Central HLA Antibody Test

Demonstrate the relationship between dd-cfDNA levels and HLA antibodies in blood transplant recipient and Demonstrate the Molecular Microscope® (MMDx) Diagnostic System results in indication and protocol biopsies from lung transplants.

Read the detailed description

The current standard for assessment of rejection in lung transplants is a transbronchial biopsy (TBB) interpreted by histology according to International Society of Heart and Lung Transplantation (ISHLT) guidelines. This has considerable error rates, many due to the high disagreement among pathologists. There is a need for new methods of assessing TBBs. Furthermore, by analyzing different types of biopsies (TBBs and endobronchial - 3BMBs), we hope to improve the safety of the biopsy procedure, while maintaining its accuracy. The emergence of blood donor-derived cell-free DNA (dd-cfDNA) measurement offers a new opportunity for screening for rejection. To address the unmet need for precision and accuracy, the Alberta Transplant Applied Genomics Centre (ATAGC, University of Alberta) has developed a new diagnostic system - the Molecular Microscope® Diagnostic System (MMDx), which uses microarrays to define the genome-wide gene expression and interpret lung transplant rejection and injury ((chronic lung allograft dysfunction (CLAD) related changes)). Now a new screening test is being introduced: the monitoring of dd-cfDNA released in the blood by the heart during rejection. The Natera Inc dd-cfDNA Prospera® test is based on the massively multiplex polymerase chain reaction that targets 13,392 single nucleotide polymorphisms and targeted sequences are quantified by Next Generation Sequencing. The Prospera® test has been done on kidney transplant recipients and detected "active rejection" and differentiated it from borderline rejection and no rejection. However, Prospera® test was not examined (the dd-cfDNA results) in lung transplant recipients. dd-cf-DNA test for lung transplants must now be calibrated against MMDx that is based on global gene expression, the new standard for biopsy interpretation. The present study will calibrate centrally measured (Natera Inc) dd-cfDNA levels obtained at the time of an indication or protocol biopsy against the MMDx measurements of T cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR-like) and tissue injury. The present study will compare dd-cfDNA and MMDx in 600 prospectively collected TBBs and 3BMBs for clinical indications and protocol, and accompanying 1800 blood samples, to calibrate the dd-cfDNA (Natera Inc.) levels against the MMDx biopsy diagnoses of TCMR, ABMR-like (and its stages), and injury, as well as central assessment of Human Leukocyte Antibody (HLA) antibody (One Lambda), interpreted centrally as donor specific antibody (DSA) based on the tissue typing results. This study is an extension of the INTERLUNG ClinicalTrials.gov identifier: NCT02812290.

Currently the study accrued 141 paired TBBs and 3BMBs, 182 TBBs, 267 corresponding blood samples for dd-cfDNA test and 159 for DSA test.

Keywords
Donor derived cfDNA, Gene expression, Lung transplant biopsy, Blood

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Calibration of Prospera® test for T cell mediated rejection

    Set dd-cfDNA test cut-off values against the probability of T cell-mediated rejection in the biopsy (TBB and 3BMB) as reported by MMDx. Calibration of dd-cfDNA test cut-off values against the probability of T cell-mediated rejection in the biopsy as reported by MMDx.

    Measured: 18 months

  2. Calibration of Prospera® test for antibody-mediated rejection

    Set dd-cfDNA test cut-off values against the probability of antibody-mediated rejection in the biopsy (TBB and 3BMB) as reported by MMDx.

    Measured: 18 months

  3. Calibration of Prospera® test for lung injury

    Set dd-cfDNA test cut-off values against the probability of acute and chronic lung injury in the biopsy (TBB and 3BMB)as reported by MMDx.

    Measured: 18 months

  4. Report calibrated Prospera® test results for rejection

    Report new dd-cfDNA test cut-off values for rejection

    Measured: 6 months

  5. Report calibrated Prospera® test results for lung injury

    Report new DD-cfDNA test cut-off values for lung injury

    Measured: 6 months

Secondary outcomes (4)

  1. Assessment of donor-specific antibody status

    Record and compare the DSA status (positive or negative) based on centralized and local HLA antibody to histology diagnoses..

    Measured: 6 months

  2. .Estimate the false positive rate of dd-cfDNA for MMDx and histology in indication and protocol biopsies

    Calculate the sensitivity and specificity of dd-cfDNA for MMDx and histology diagnoses.

    Measured: 6 months

  3. Determine whether calibrated dd-cfDNA blood test will replace biopsies

    Determine if dd-cfDNA test will avoid need for indication biopsy when transplant function deteriorates - yes or no. This will be based on the consensus between participating clinicians.

    Measured: 6 months

  4. Determine whether calibrated dd-cfDNA blood test predicts the effect of treatment

    Determine the values for dd-cfDNA for grades of response to treatment: no change, partial response, complete resolution.

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 May 2023
  2. Study start1 Nov 2023
  3. Primary completionNov 2027 (estimated)
  4. Study completionDec 2028 (estimated)

Resources

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
Prospective
Enrolment
600 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05837663
Sponsor's protocol ID
Pro00048176
Status last verified
Jul 2026
First submitted
3 Apr 2023
Last updated
17 Jul 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Only IPD data will be shared within a participating center

Questions about this trial

What is this clinical trial studying?

An observational study of Lung Transplantation, run by University of Alberta at 19 sites in 5 countries.

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 1 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: looking for participants now, as of the sponsor's last update on 17 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States, Canada, Czechia, Australia, Austria. 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Konrad S Famulski, PhD DSc (1 780 782 9463, konrad@ualberta.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Calibration of Prospera® test for T cell mediated rejection (time frame: 18 months). The study lists 5 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 NCT05837663.

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 17 Jul 2026.

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