Non Invasive Blood Test To Diagnose Acute Rejection After Kidney Transplantation

Kidney Transplant Recipients Clinical Trial

— DART  

Official title:

Circulating Donor-Derived Cell-free DNA in Blood for Diagnosing Acute Rejection in Kidney Transplant Recipients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02424227
• Other study ID #: SN-C-00006
• Status: Active, not recruiting
• Start date: April 2015
• Est. completion date: January 31, 2019

Study information

• Verified date: December 2018
• Source: CareDx
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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]).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 401
• Est. completion date: January 31, 2019
• Est. primary completion date: August 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Kidney Transplant Recipients

Locations

Country	Name	City	State
United States	University of Maryland	Baltimore	Maryland
United States	University of Alabama, Birmingham	Birmingham	Alabama
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Baylor Research Institute	Fort Worth	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	University of California Los Angeles	Los Angeles	California
United States	University of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Columbia University	New York	New York
United States	University of Pennsylvannia	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Washington University	Saint Louis	Missouri
United States	Baylor Scott and White	Temple	Texas

Sponsors (1)

Lead Sponsor	Collaborator
CareDx

Country where clinical trial is conducted

United States, 

References & Publications (7)

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

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. — View Citation

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]. — View Citation

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. — View Citation

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

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. — 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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical T cell as well as antibody mediated acute rejection		Occurring within 12 months post transplant
Primary	Sub-clinical T cell as well as antibody mediated acute rejection		Occurring within 12 months post transplant
Primary	Composite of clinical and sub-clinical T cell as well as antibody mediated acute rejection		Occurring within 12 months post transplant
Secondary	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
Secondary	Renal allograft injury from BKV nephritis, CNI toxicity, acute pyeloenephrtiis and recurrent disease confirmed by renal histology		24 months