TruGraf® Long-term Clinical Outcomes Study

Kidney Transplant Rejection Clinical Trial

Official title:

TruGraf® Long-term Clinical Outcomes Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04491552
• Other study ID #: TGRP06
• Status: Recruiting
• Start date: September 9, 2020
• Est. completion date: November 2023

Study information

• Verified date: November 2022
• Source: Transplant Genomics, Inc.
• Contact: Isioma Agboli, MD
• Phone: 510-767-8609
• Email: isiomaagboli[@]eurofins-tgi.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a prospective, multi-center, observational study. Subjects will have OmniGraf™ (TruGraf® and TRAC™) testing at study enrollment and thereafter every 3 months. In addition subjects will have OmniGraf™ (TruGraf® and TRAC™) testing at any time there is a clinical suspicion of acute rejection. Data collection for the primary objective extends over a 2-year period.

Description:

Several studies have validated TruGraf® in stable renal transplant patients to rule out subclinical acute rejection. These studies generally evaluated the diagnostic value of TruGraf® at single timepoints. Thus the value of serial monitoring and changes over time has not been previously investigated. In addition, no study has assessed TruGraf® and TRAC™in a serial and longitudinal fashion. Therefore the aim of this study is to evaluate the impact of serial monitoring renal transplant patients with both TruGraf® and TRAC™ on long term outcomes.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: November 2023
• Est. primary completion date: September 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent and HIPAA authorization;
• At least 18 years of age;
• Recipient of a primary or subsequent deceased-donor or living-donor kidney transplant;
• At least 3-months post-transplant;
• Stable serum creatinine (per Principal Investigator);
• Treated with any immunosuppressive regimen, and;
• Selected by provider to undergo OmniGraf™ (TruGraf® and TRAC™) testing as part of post-transplant care; and

Exclusion Criteria:

• Recipient of a combined organ transplant with an extra-renal organ and/or islet cell transplant;
• Recipient of a previous non-renal solid organ and/or islet cell transplant;
• Known to be pregnant;
• Known to be infected with HIV;
• Known to have Active BK nephropathy;
• Known to have nephrotic proteinuria (Per Principal Investigator);
• Participation in other biomarker studies testing clinical utility.

Related Conditions & MeSH terms

• Kidney Transplant Rejection

Intervention

Diagnostic Test:
• Patients monitored with TruGraf and TRAC testing
This is an observational study there are no protocol mandated interventions. TruGraf and TRAC results will be utilized in conjunction with standard of care assessments to determine patient management.

Locations

Country	Name	City	State
United States	University of New Mexico Health Sciences Center	Albuquerque	New Mexico
United States	Universtiy of Maryland Medical Center	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Erie County Medical Center	Buffalo	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	University of Illinois-Chicago Medical Center	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Fresno Nephrology Medical Group	Fresno	California
United States	Vidant Medical Center	Greenville	North Carolina
United States	Clinical Research Strategies	Houston	Texas
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Scripps Memorial Hospital La Jolla	La Jolla	California
United States	Keck Hospital of USC	Los Angeles	California
United States	Tulane University Hospital and Clinic	New Orleans	Louisiana
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Virginia Commonwealth University	Richmond	Virginia
United States	House of Transplant and Cancer- Riverside Community Hospital	Riverside	California
United States	University of Rochester Medical Center	Rochester	New York
United States	UR Medicine Strong Memorial Hospital	Rochester	New York
United States	University of California Davis	Sacramento	California
United States	Primary Coordinator Coordinator	Saint Louis	Missouri
United States	University of Utah Hospital	Salt Lake City	Utah
United States	Utah Kidney Research Institute	Salt Lake City	Utah
United States	California Pacific Medical Center	San Francisco	California
United States	Primary Coordinator	Seattle	Washington
United States	Willis-Knighton Medical Center	Shreveport	Louisiana
United States	Renal and Transplant Associates of New England	Springfield	Massachusetts
United States	Banner University Medical Center Tucson	Tucson	Arizona
United States	MedStar Georgetown University Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Transplant Genomics, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (13)

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. — View Citation

El Ters M, Grande JP, Keddis MT, Rodrigo E, Chopra B, Dean PG, Stegall MD, Cosio FG. Kidney allograft survival after acute rejection, the value of follow-up biopsies. Am J Transplant. 2013 Sep;13(9):2334-41. doi: 10.1111/ajt.12370. Epub 2013 Jul 19. — View Citation

First MR, Pierry, D, McNultuy, M et al. Analytical and clinical validation of a molecular diagnostic signature in kidney transplant recipients. J Transplant. Technol. Res. 2017; 7(3).

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. Review. — View Citation

Hart A, Smith JM, Skeans MA, Gustafson SK, Stewart DE, Cherikh WS, Wainright JL, Boyle G, Snyder JJ, Kasiske BL, Israni AK. Kidney. Am J Transplant. 2016 Jan;16 Suppl 2:11-46. doi: 10.1111/ajt.13666. — View Citation

Loupy A, Vernerey D, Tinel C, Aubert O, Duong van Huyen JP, Rabant M, Verine J, Nochy D, Empana JP, Martinez F, Glotz D, Jouven X, Legendre C, Lefaucheur C. Subclinical Rejection Phenotypes at 1 Year Post-Transplant and Outcome of Kidney Allografts. J Am Soc Nephrol. 2015 Jul;26(7):1721-31. doi: 10.1681/ASN.2014040399. Epub 2015 Jan 2. — View Citation

Marsh CL, Kurian SM, Rice JC, Whisenant TC, David J, Rose S, Schieve C, Lee D, Case J, Barrick B, Peddi VR, Mannon RB, Knight R, Maluf D, Mandelbrot D, Patel A, Friedewald JJ, Abecassis MM, First MR. Application of TruGraf v1: A Novel Molecular Biomarker for Managing Kidney Transplant Recipients With Stable Renal Function. Transplant Proc. 2019 Apr;51(3):722-728. doi: 10.1016/j.transproceed.2019.01.054. Epub 2019 Jan 26. — View Citation

Meier-Kriesche HU, Schold JD, Srinivas TR, Kaplan B. Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era. Am J Transplant. 2004 Mar;4(3):378-83. — View Citation

Rush D, Nickerson P, Gough J, McKenna R, Grimm P, Cheang M, Trpkov K, Solez K, Jeffery J. Beneficial effects of treatment of early subclinical rejection: a randomized study. J Am Soc Nephrol. 1998 Nov;9(11):2129-34. — View Citation

Sharon E, Shi H, Kharbanda S, Koh W, Martin LR, Khush KK, Valantine H, Pritchard JK, De Vlaminck I. Quantification of transplant-derived circulating cell-free DNA in absence of a donor genotype. PLoS Comput Biol. 2017 Aug 3;13(8):e1005629. doi: 10.1371/journal.pcbi.1005629. eCollection 2017 Aug. — View Citation

Snyder TM, Khush KK, Valantine HA, Quake SR. Universal noninvasive detection of solid organ transplant rejection. Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):6229-34. doi: 10.1073/pnas.1013924108. Epub 2011 Mar 28. — View Citation

Tonelli M, Wiebe N, Knoll G, Bello A, Browne S, Jadhav D, Klarenbach S, Gill J. Systematic review: kidney transplantation compared with dialysis in clinically relevant outcomes. Am J Transplant. 2011 Oct;11(10):2093-109. doi: 10.1111/j.1600-6143.2011.03686.x. Epub 2011 Aug 30. — View Citation

US Renal Data System. 2016 USRDS annual data report: Epidemiology of kidney disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2016.

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	occurrence of either biopsy proven acute rejection (BPAR) on a for cause biopsy or graft loss, or a decrease from baseline in eGFR > 10 mL/min.		Baseline to month 24
Secondary	First occurrence of biopsy proven acute rejection (on a for cause biopsy)		Baseline to month 24
Secondary	First occurrence of clinically treated acute rejection		Baseline to month 24
Secondary	Proteinuria	defined by a spot urine protein-creatinine ratio > 0.5	Baseline to month 24
Secondary	TruGraf results	The proportion of TruGraf not-TX results	Baseline to month 24
Secondary	TRAC results	The proportion of TRAC results > 0.69	Baseline to month 24
Secondary	Clinical Utility of TruGraf and TRAC in clinical decision making	Percent of total number of TruGraf results that the PI identified as having clinical utility	Baseline to month 24
Secondary	Proportion of subjects who develop de novo donor-specific HLA antibodies class I and class II (dnDSA)	Proportion of subjects who develop de novo donor-specific HLA antibodies class I and class II (dnDSA)	Baseline to month 24
Secondary	Proportion of subjects with graft loss	defined as permanent return to dialysis, retransplantation or patient death at any time during the 2-year primary follow-up study period	Baseline to month 24
Secondary	Graft survival	calculated from the date of kidney transplantation until data of graft loss	Baseline to month 24
Secondary	Proportion of subjects with death-censored graft loss	defined as permanent return to dialysis or retransplantation at any time during the 2-year primary follow-up study period. Patients who die with a functioning graft will be right censored	Baseline to month 24
Secondary	Percent subject death period	Subject death from any cause at any time	Baseline to month 24
Secondary	Subject survival	calculated from date of kidney transplantation until date of patient death	Baseline to month 24
Secondary	Estimated GFR	calculated using the MDRD 4-variable equation	Baseline to month 24