Non Invasive Blood Test To Diagnose Acute Rejection After Kidney Transplantation (DART)

• ClinicalTrials.gov Identifier: NCT02424227
• Recruitment Status: Unknown
• First Posted: April 22, 2015
• Last Update Posted: December 17, 2018
• Sponsor: CareDx
• Information provided by (Responsible Party): CareDx

Study Description

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

Condition or disease
Kidney Transplant Recipients

Detailed Description:

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 periodically and also after the treatment of acute rejection up to 8 weeks post treatment. The blood samples and all relevant clinical data will be provided to CareDx scientists for laboratory assay of dd-cfDNA levels and correlation of dd-cfDNA levels with the clinical features of the subjects.

The primary objective of the study is to correlate circulating dd-cfDNA to clinical and sub-clinical acute rejection in renal allograft recipients. The secondary objective of the study is to correlate circulating dd-cfDNA to renal function, both serum creatinine and estimated glomerular filtration rate [eGFR]).

Study Design

• Study Type: Observational
• Actual Enrollment: 401 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: Circulating Donor-Derived Cell-free DNA in Blood for Diagnosing Acute Rejection in Kidney Transplant Recipients
• Study Start Date: April 2015
• Actual Primary Completion Date: August 30, 2018
• Estimated Study Completion Date: January 31, 2019

Groups and Cohorts

Group/Cohort
Kidney Transplant Recipients; Adult living and deceased donor kidney transplant recipients will be eligible to participate in this study.

Outcome Measures

Primary Outcome Measures :

1. Clinical T cell as well as antibody mediated acute rejection [ Time Frame: Occurring within 12 months post transplant ]
2. Sub-clinical T cell as well as antibody mediated acute rejection [ Time Frame: Occurring within 12 months post transplant ]
3. Composite of clinical and sub-clinical T cell as well as antibody mediated acute rejection [ Time Frame: Occurring within 12 months post transplant ]

Secondary Outcome Measures :

1. 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 [ Time Frame: 24 months ]
2. Renal allograft injury from BKV nephritis, CNI toxicity, acute pyeloenephrtiis and recurrent disease confirmed by renal histology [ Time Frame: 24 months ]

Biospecimen Retention:   Samples With DNA

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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.

Criteria

Inclusion Criteria

1. Adult recipients (Age > 18 years )
2. Both genders and all racial and ethnic groups
3. Kidney transplant alone
4. Both living and deceased donor transplants
5. 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.
6. Ability to come for follow-up and undergo biopsy (Performed in accordance to SOC)
7. 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.

Exclusion Criteria

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

Contacts and Locations

Locations

United States, Alabama

University of Alabama, Birmingham

Birmingham, Alabama, United States, 35294

United States, California

University of California Los Angeles

Los Angeles, California, United States, 90024

Cedars-Sinai Medical Center

Los Angeles, California, United States, 90048

United States, Indiana

Indiana University

Indianapolis, Indiana, United States, 46202

United States, Maryland

University of Maryland

Baltimore, Maryland, United States, 21201

United States, Minnesota

University of Minnesota

Minneapolis, Minnesota, United States, 55414

United States, Missouri

Washington University

Saint Louis, Missouri, United States, 63110

United States, New York

Columbia University

New York, New York, United States, 10032

United States, Ohio

Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44195

United States, Pennsylvania

University of Pennsylvannia

Philadelphia, Pennsylvania, United States, 19104

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States, 15213

United States, Tennessee

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37232

United States, Texas

Baylor Research Institute

Fort Worth, Texas, United States, 76104

Baylor Scott and White

Temple, Texas, United States, 76502

Sponsors and Collaborators

CareDx

Investigators

• Study Director: James Yee, MD; CareDx

More Information

Publications:

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. Erratum in: Am J Transplant. 2015 Oct;15(10):2784. Rangel, Erika [corrected to Rangel, Erika B].

Lo YM. Transplantation monitoring by plasma DNA sequencing. Clin Chem. 2011 Jul;57(7):941-2. doi: 10.1373/clinchem.2011.166686.

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.

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

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.

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: CareDx
• ClinicalTrials.gov Identifier: NCT02424227
• Other Study ID Numbers: SN-C-00006
• First Posted: April 22, 2015
• Last Update Posted: December 17, 2018
• Last Verified: December 2018