Trifecta-Kidney cfDNA-MMDx Study
1 other identifier
observational
300
10 countries
31
Brief Summary
Demonstrate the relationship between DD-cfDNA levels and HLA antibodies in blood, and the Molecular Microscope® (MMDx) Diagnostic System results in indication biopsies.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Dec 2019
Longer than P75 for all trials
31 active sites
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 1, 2019
CompletedFirst Submitted
Initial submission to the registry
January 14, 2020
CompletedFirst Posted
Study publicly available on registry
January 27, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2027
March 18, 2026
March 1, 2026
7 years
January 14, 2020
March 16, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
Calibration of Prospera test for T cell-mediated rejection
Calibration of DD-cfDNA test cut-off values against the probability of T cell-mediated rejection in the biopsy as reported by MMDx.
18 months
Calibration of Prospera test for antibody-mediated rejection
Calibration of DD-cfDNA test cut-off values against the probability of antibody-mediated rejection in the biopsy as reported by MMDx.
18 months
Calibration of Prospera test for kidney injury
Calibration of DD-cfDNA test cut-off values against the probability of acute and chronic kidney injury in the biopsy as reported by MMDx.
18 months
Report calibrated Prospera test results for rejection
Report new DD-cfDNA test cut-off values for rejection
6 months
Report calibrated Prospera test results for kidney injury
Report new DD-cfDNA test cut-off values for acute and chronic kidney injury
6 month
Secondary Outcomes (2)
Determine if Prospera blood test can replace kidney biopsy test
6 months
Assessment of donor-specific antibody status
6 months
Study Arms (1)
Kidney transplant biopsies for cause
The study population includes patients with a functioning kidney transplant undergoing a biopsy for clinical indications as standard of care.
Interventions
Transplant patient blood sample
Portion of kidney transplant indication biopsy
Transplant patient blood sample
Eligibility Criteria
The study population includes patients with a functioning kidney transplant undergoing a biopsy for clinical indications as standard of care to determine the cause of their graft dysfunction (deterioration in graft function, delayed graft function, proteinuria).
You may qualify if:
- All kidney transplant recipients undergoing a kidney biopsy for clinical indications, as determined by their physician or surgeon, will be eligible to enroll in the study.
You may not qualify if:
- Patients will be excluded from the study if they decline participation or are unable to give informed consent or multiple organ recipients.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Albertalead
- Natera, Inc.collaborator
- One Lambdacollaborator
Study Sites (31)
Tampa General Hospital
Tampa, Florida, 33606, United States
University of Maryland School of Medicine
Baltimore, Maryland, 21201, United States
The Johns Hopkins University, School of Medicine
Baltimore, Maryland, 21205, United States
Detroit Medical Center, Harper University Hospital of Wayne State University
Detroit, Michigan, 48201, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
Barnes-Jewish Hospital, Washington University at St. Louis
St Louis, Missouri, 63110, United States
University Hospitals Cleveland Medical Ctr.
Cleveland, Ohio, 44106-5048, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Intermountain Transplant Services
Murray, Utah, 84107, United States
Virginia Commonwealth University Medical Center
Richmond, Virginia, 23298, United States
Division of Nephrology & UW Organ Transplant Center University of Washington
Seattle, Washington, 98195, United States
Department of Nephrology, The Royal Melbourne Hospital 1 South East
Melbourne, VIC 3050, Australia
University of Alberta, Department of Medicine
Edmonton, Alberta, T6G 2G3, Canada
ST. Paul's Hospital, 6A Providence Building, 1081 Burrard Street
Vancouver, British Columbia, V6Z 1Y6, Canada
University Hospital Merkur Renal Division
Zagreb, 1910000, Croatia
Institute for Clinical and Experimental Medicine (IKEM)
Prague, 140 21 Praha 4, Czechia
Charite-Medical University of Berlin Department of Nephrology
Berlin, 10117, Germany
Centre of Nephrology, Vilnius University Hospital Santaros Klinikos
Vilnius, LT-08661, Lithuania
Department of Nephrology and Transplantation Medical University in Bialystok
Bialystok, 15-540, Poland
University Hospital nr1 Bydgoszcz, Klinika Transplantologii
Bydgoszcz, 85-094, Poland
Medical University of Gdańsk Klinika Nefrologii Transplantologii i Chorób Wewnętrznych
Gdansk, 80-259, Poland
Medical University of Silesia
Katowice, 40-027, Poland
Department of Transplantation and General Surgery, Wojewodzki Hospital
Poznan, 60-479, Poland
Department of Nephrology, Transplantation and Internal Medicine, University Hospital n.2
Szczecin, 70-111, Poland
Pomeranian Medical University, Samodzielny Publiczny Woj. Szpital Zespolony, Oddzial Nefrologii i Transplantacji Nerek
Szczecin, 71-455, Poland
Medical University of Warsaw, Department of Transplantation Medicine, Nephrology and Internal Diseases
Warsaw, 02-006, Poland
Transplant Medicine & Nephrology Clinic, Medical University of Warsaw
Warsaw, 02-006, Poland
The Children's Memorial Health Institute, Department of Nephrology, Kidney Transplantation and Hypertension
Warsaw, 04-730, Poland
Wroclaw Medical University, Department of Nephrology and Transplantation Medicine
Wroclaw, 50-556, Poland
Department of Nephrology, University Medical Centre
Ljubljana, 21000, Slovenia
University Hospital Zurich
Zurich, 8091, Switzerland
Related Publications (12)
Madill-Thomsen KS, Halloran PF. Precision diagnostics in transplanted organs using microarray-assessed gene expression: concepts and technical methods of the Molecular Microscope(R) Diagnostic System (MMDx). Clin Sci (Lond). 2024 Jun 5;138(11):663-685. doi: 10.1042/CS20220530.
PMID: 38819301BACKGROUNDHalloran PF, Madill-Thomsen KS. Donor-derived Cell-free DNA: A Step Forward in the Quest for Transplant Truth. Transplantation. 2025 Jun 1;109(6):910-914. doi: 10.1097/TP.0000000000005332. Epub 2025 Jan 28. No abstract available.
PMID: 39883025BACKGROUNDHalloran PF, Reeve J, Madill-Thomsen KS, Demko Z, Prewett A, Billings P; Trifecta Investigators. The Trifecta Study: Comparing Plasma Levels of Donor-derived Cell-Free DNA with the Molecular Phenotype of Kidney Transplant Biopsies. J Am Soc Nephrol. 2022 Feb;33(2):387-400. doi: 10.1681/ASN.2021091191. Epub 2022 Jan 20.
PMID: 35058354RESULTHalloran PF, Reeve J, Madill-Thomsen KS, Demko Z, Prewett A, Gauthier P, Billings P, Lawrence C, Lowe D, Hidalgo LG; the Trifecta Investigators. Antibody-mediated Rejection Without Detectable Donor-specific Antibody Releases Donor-derived Cell-free DNA: Results From the Trifecta Study. Transplantation. 2023 Mar 1;107(3):709-719. doi: 10.1097/TP.0000000000004324. Epub 2023 Feb 21.
PMID: 36190186RESULTHalloran PF, Madill-Thomsen KS, Reeve J. The Molecular Phenotype of Kidney Transplants: Insights From the MMDx Project. Transplantation. 2024 Jan 1;108(1):45-71. doi: 10.1097/TP.0000000000004624. Epub 2023 Dec 13.
PMID: 37310258RESULTHalloran PF, Reeve J, Madill-Thomsen KS, Kaur N, Ahmed E, Cantos C, Al Haj Baddar N, Demko Z, Liang N, Swenerton RK, Zimmermann BG, Van Hummelen P, Prewett A, Rabinowitz M, Tabriziani H, Gauthier P, Billings P; Trifecta Investigators*. Combining Donor-derived Cell-free DNA Fraction and Quantity to Detect Kidney Transplant Rejection Using Molecular Diagnoses and Histology as Confirmation. Transplantation. 2022 Dec 1;106(12):2435-2442. doi: 10.1097/TP.0000000000004212. Epub 2022 Nov 22.
PMID: 35765145RESULTGauthier PT, Madill-Thomsen KS, Demko Z, Prewett A, Gauthier P, Halloran PF; Trifecta-Kidney Investigators. Distinct Molecular Processes Mediate Donor-derived Cell-free DNA Release From Kidney Transplants in Different Disease States. Transplantation. 2024 Apr 1;108(4):898-910. doi: 10.1097/TP.0000000000004877. Epub 2023 Dec 27.
PMID: 38150492RESULTHidalgo LG, Madill-Thomsen KS, Reeve J, Mackova M, Gauthier P, Demko Z, Prewett A, Lee M, Alhamad T, Anand S, Arnol M, Baliga R, Banasik M, Blosser CD, Bobba S, Brennan D, Bromberg J, Budde K, Chamienia A, Chow K, Ciszek M, Costa N, Deborska-Materkowska D, Debska-Slizien A, Domanski L, Fatica R, Francis I, Fryc J, Gill J, Gill J, Glyda M, Gourishankar S, Gryczman M, Gupta G, Hruba P, Hughes P, Jittirat A, Jurekovic Z, Kamal L, Kamel M, Kant S, Kojc N, Konopa J, Kumar D, Lan J, Lowe D, Mazurkiewicz J, Miglinas M, Moinuddin I, Mueller T, Myslak M, Naumnik B, Paczek L, Patel A, Perkowska-Ptasinska A, Piecha G, Poggio E, Bloudickova SR, Regele H, Schachtner T, Shojai S, Sikosana MLN, Slatinska J, Smykal-Jankowiak K, Haler ZV, Viklicky O, Vucur K, Weir MR, Wiecek A, Zaky Z, Halloran PF. Improving the histologic detection of donor-specific antibody-negative antibody-mediated rejection in kidney transplants. Am J Transplant. 2026 Jan;26(1):117-130. doi: 10.1016/j.ajt.2025.08.029. Epub 2025 Aug 23.
PMID: 40854490RESULTMadill-Thomsen KS, Hidalgo LG, Demko ZP, Gauthier PM, Prewett A, Lowe D, Chang JJ, Mackova M, Budde K, Bromberg JS, Halloran PF; Trifecta-Kidney Study Group. Defining Relationships Among Tests for Kidney Transplant Antibody-Mediated Rejection. Kidney Int Rep. 2025 Jun 17;10(9):3225-3238. doi: 10.1016/j.ekir.2025.06.017. eCollection 2025 Sep.
PMID: 40980666DERIVEDHalloran PF, Chang J, Mackova M, Madill-Thomsen KS, Akalin E, Alhamad T, Anand S, Arnol M, Baliga R, Banasik M, Blosser CD, Bohmig G, Brennan D, Bromberg J, Budde K, Chamienia A, Chow K, Ciszek M, de Freitas D, Deborska-Materkowska D, Debska-Slizien A, Djamali A, Domanski L, Durlik M, Einecke G, Eskandary F, Fatica R, Francis I, Fryc J, Gill J, Gill J, Glyda M, Gourishankar S, Gryczman M, Gupta G, Hruba P, Hughes P, Jittirat A, Jurekovic Z, Kamal L, Kamel M, Kant S, Kojc N, Konopa J, Lan J, Mannon RB, Matas A, Mazurkiewicz J, Miglinas M, Mueller T, Myslak M, Narins S, Naumnik B, Patel A, Perkowska-Ptasinska A, Picton M, Piecha G, Poggio E, Rajnochova Bloudickova S, Schachtner T, Shojai S, Sikosana ML, Slatinska J, Smykal-Jankowiak K, Solanki A, Veceric Haler Z, Viklicky O, Vucur K, Weir MR, Wiecek A, Wlodarczyk Z, Yang H, Zaky Z, Gauthier PT, Hinze C. A cross-sectional study of the role of epithelial cell injury in kidney transplant outcomes. JCI Insight. 2025 Apr 15;10(10):e188658. doi: 10.1172/jci.insight.188658. eCollection 2025 May 22.
PMID: 40232852DERIVEDHalloran PF, Reeve J, Mackova M, Madill-Thomsen KS, Demko Z, Olymbios M, Campbell P, Melenovsky V, Gong T, Hall S, Stehlik J. Comparing Plasma Donor-derived Cell-free DNA to Gene Expression in Endomyocardial Biopsies in the Trifecta-Heart Study. Transplantation. 2024 Sep 1;108(9):1931-1942. doi: 10.1097/TP.0000000000004986. Epub 2024 Aug 20.
PMID: 38538559DERIVEDHalloran PF, Madill-Thomsen KS. The Molecular Microscope Diagnostic System: Assessment of Rejection and Injury in Heart Transplant Biopsies. Transplantation. 2023 Jan 1;107(1):27-44. doi: 10.1097/TP.0000000000004323. Epub 2022 Dec 8.
PMID: 36508644DERIVED
Biospecimen
RNA isolated from kidney biopsies
Study Officials
- PRINCIPAL INVESTIGATOR
Philip F Halloran, MD, PhD
University of Alberta
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Distinguished Professor
Study Record Dates
First Submitted
January 14, 2020
First Posted
January 27, 2020
Study Start
December 1, 2019
Primary Completion (Estimated)
December 1, 2026
Study Completion (Estimated)
December 1, 2027
Last Updated
March 18, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share