Non Invasive Blood Test To Diagnose Acute Rejection After Kidney Transplantation

NCT02424227 | Unknown

• 1 other identifier: SN-C-00006
• Study Type: observational
• Target: 401
• Locations: 1 country
• Sites: 14

Brief Summary

This is a prospective, multicenter, observational study of kidney transplant subjects where blood specimens, intended for dd-cfDNA and other future research purposes, will be drawn after transplant

Conditions

Kidney Transplant Recipients

Outcome Measures

Primary Outcomes (3)

• Clinical T cell as well as antibody mediated acute rejection

  Occurring within 12 months post transplant

• Sub-clinical T cell as well as antibody mediated acute rejection

  Occurring within 12 months post transplant

• Composite of clinical and sub-clinical T cell as well as antibody mediated acute rejection

  Occurring within 12 months post transplant

Secondary Outcomes (2)

• eGFR (estimated Glomerular Filtration Rate [mL/min]): will be derived from serum creatinine level, corrected for variables, using the CKD-RPI (Chronic Kidney Disease Epidemiology Collaboration) equation

  24 months

• Renal allograft injury from BKV nephritis, CNI toxicity, acute pyeloenephrtiis and recurrent disease confirmed by renal histology

  24 months

Study Arms (1)

Kidney Transplant Recipients

Adult living and deceased donor kidney transplant recipients will be eligible to participate in this study.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult de novo living and deceased donor kidney transplant recipients will be eligible to participate in this study.

You may qualify if:

• Adult recipients (Age \> 18 years )
• Both genders and all racial and ethnic groups
• Kidney transplant alone
• Both living and deceased donor transplants
• Primary and re-transplants. A total of 30 re-transplant recipients across all study sites will be eligible for enrollment. CareDx will notify all centers when this subset of enrollment has been met. Thereafter, all enrolled patients should be primary transplant recipients.
• Ability to come for follow-up and undergo biopsy (Performed in accordance to SOC)
• Ability to give written informed consent prior to study enrollment
• Patients can be enrolled at any time; before or after transplantation and/or at time of outpatient or inpatient visits for workup of medical problems; e.g. at the time of a renal biopsy (regardless of elapsed time since post transplant) as specified in this study protocol.

You may not qualify if:

• Pediatric recipients (Age \< 18 years)
• Pregnant women
• Patients undergoing multi-organ transplants (e.g. kidney with pancreas or liver)
• Patients receiving donor organ from an identical twin

Sponsors & Collaborators

• CareDx: lead

Study Sites (14)

University of Alabama, Birmingham

Birmingham, Alabama, 35294, United States

Location

University of California Los Angeles

Los Angeles, California, 90024, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55414, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

University of Pennsylvannia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Baylor Research Institute

Fort Worth, Texas, 76104, United States

Location

Baylor Scott and White

Temple, Texas, 76502, United States

Location

Related Publications (9)

• Haas M, Sis B, Racusen LC, Solez K, Glotz D, Colvin RB, Castro MC, David DS, David-Neto E, Bagnasco SM, Cendales LC, Cornell LD, Demetris AJ, Drachenberg CB, Farver CF, Farris AB 3rd, Gibson IW, Kraus E, Liapis H, Loupy A, Nickeleit V, Randhawa P, Rodriguez ER, Rush D, Smith RN, Tan CD, Wallace WD, Mengel M; Banff meeting report writing committee. Banff 2013 meeting report: inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant. 2014 Feb;14(2):272-83. doi: 10.1111/ajt.12590.

  PMID: 24472190 BACKGROUND

• Lo YM. Transplantation monitoring by plasma DNA sequencing. Clin Chem. 2011 Jul;57(7):941-2. doi: 10.1373/clinchem.2011.166686. No abstract available.

  PMID: 21566070 BACKGROUND

• 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.

  PMID: 21444804 BACKGROUND

• Code of Federal Regulations, Title 42 - Public Health, Part 493 - Laboratory Requirements, Subpart A - General Provisions, Sections 1, 2 & 3

  BACKGROUND

• Hidestrand M, Tomita-Mitchell A, Hidestrand PM, Oliphant A, Goetsch M, Stamm K, Liang HL, Castleberry C, Benson DW, Stendahl G, Simpson PM, Berger S, Tweddell JS, Zangwill S, Mitchell ME. Highly sensitive noninvasive cardiac transplant rejection monitoring using targeted quantification of donor-specific cell-free deoxyribonucleic acid. J Am Coll Cardiol. 2014 Apr 1;63(12):1224-1226. doi: 10.1016/j.jacc.2013.09.029. Epub 2013 Oct 16. No abstract available.

  PMID: 24140666 BACKGROUND

• Sigdel TK, Vitalone MJ, Tran TQ, Dai H, Hsieh SC, Salvatierra O, Sarwal MM. A rapid noninvasive assay for the detection of renal transplant injury. Transplantation. 2013 Jul 15;96(1):97-101. doi: 10.1097/TP.0b013e318295ee5a.

  PMID: 23756769 BACKGROUND

• 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: 24944192 BACKGROUND

• Sawinski DL, Mehta S, Alhamad T, Bromberg JS, Fischbach B, Aeschbacher T, Ghosh S, Shekhtman G, Dholakia S, Brennan DC, Poggio E, Bloom RD, Jordan SC. Association between dd-cfDNA levels, de novo donor specific antibodies, and eGFR decline: An analysis of the DART cohort. Clin Transplant. 2021 Sep;35(9):e14402. doi: 10.1111/ctr.14402. Epub 2021 Jul 14.

  PMID: 34184326 DERIVED

• Bromberg JS, Brennan DC, Poggio E, Bunnapradist S, Langone A, Sood P, Matas AJ, Mannon RB, Mehta S, Sharfuddin A, Fischbach B, Narayanan M, Jordan SC, Cohen DJ, Zaky ZS, Hiller D, Woodward RN, Grskovic M, Sninsky JJ, Yee JP, Bloom RD. Biological Variation of Donor-Derived Cell-Free DNA in Renal Transplant Recipients: Clinical Implications. J Appl Lab Med. 2017 Nov 1;2(3):309-321. doi: 10.1373/jalm.2016.022731.

  PMID: 33636851 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

cfDNA samples collected in Cell-Free DNA BCT and mRNA collected in PAX gene tubes will be retained

Study Officials

• James Yee, MD

  CareDx

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2015
• First Posted: April 22, 2015
• Study Start: April 1, 2015
• Primary Completion: August 30, 2018
• Study Completion: January 31, 2019
• Last Updated: December 17, 2018

Record last verified: 2018-12

Locations

US (14)