Evaluation of Patient Outcomes From the Kidney Allograft Outcomes AlloSure Registry

Kidney Transplant Rejection Clinical Trial

— KOAR  

Official title:

Evaluation of Patient Outcomes From the Kidney Allograft Outcomes AlloSure Registry

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03326076
• Other study ID #: KOAR
• Status: Active, not recruiting
• Start date: January 23, 2018
• Est. completion date: December 31, 2025

Study information

• Verified date: June 2023
• Source: CareDx
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is an observational study to evaluate safety and efficacy outcomes in renal transplant recipients in whom post-transplant care is managed using AlloSure®. AlloSure® is a non-invasive test to measure donor-derived cell-free DNA (dd-cfDNA). The AlloSure test is intended to assess the probability of allograft rejection in kidney transplant recipients with clinical suspicion of rejection and to inform clinical decision-making regarding the necessity of renal biopsy in such patients at least 2 weeks post-transplant in conjunction with standard clinical assessment.

Amendment 1 (A1): Is an observational study to develop and validate the clinical use of KidneyCare®.

Description:

The AlloSure test has been approved for Medicare coverage for clinical use when a physician determines there is a need to assess the probability of allograft rejection in kidney transplant recipients. The DART study suggests that use of the non-invasive AlloSure test to measure donor-derived cell-free DNA (dd-cfDNA) can be used to discriminate active rejection in a renal transplant recipient. Use of the test may reduce invasive percutaneous renal biopsy procedures among patients with a suspicion of rejection.

Amendment 1 (A1) is intended to enable the development of KidneyCare® which is a panel test which includes the clinically validated commercial AlloSure dd-cfDNA test, combined with AlloMap Kidney which is a peripheral blood gene expression profiling test currently under development, and iBox, which is an analytic platform that predicts allograft survival at 3, 5, 7 and 10 years using a proprietary software algorithm based on a number of clinical inputs. The AlloMap Kidney and the iBox components are not yet clinically validated and so will not be used for patient management and are being developed through this study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 4000
• Est. completion date: December 31, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

KOAR Inclusion Criteria:

1. Patient's health care provider adopts and intends to apply the center's AlloSure Routine Testing Schedule as part of the information used to manage the patient.

2. Subjects willing to provide written informed consent to participate.

KOAR Exclusion Criteria:

___________________________________________________________

Exclusions for AlloSure® Intended Use

Specimens from patients for whom any of the following are true will not be tested:

1. Recipients of transplanted organs other than kidney

2. Recipients of a transplant from a monozygotic (identical)

3. Recipients of a bone marrow transplant

4. Recipients who are pregnant

5. Recipients who are under the age of 18

6. Recipient who are less than 14 days post-transplant

Related Conditions & MeSH terms

• Kidney Transplant Rejection

Intervention

Diagnostic Test:
• Donor-derived cell-free DNA (AlloSure®)
Patients will receive donor-derived cell-free DNA testing for surveillance and for-cause. The planned surveillance will occur at months 1, 2, 3, 4, 6, 9, and 12 post-transplant and quarterly in year 2 and year 3.

Other:
• Standard care
Current standard methods for monitoring of renal allograft recipients for rejection (e.g. donor-specific antibodies, serum creatinine, proteinuria, renal allograft biopsy)

Diagnostic Test:
• Peripheral blood gene expression profiling (AlloMap Kidney)
Patients will receive peripheral blood gene expression profiling testing for surveillance and for-cause. The planned surveillance will occur at months 1, 2, 3, 4, 6, 9, and 12 post-transplant and quarterly in year 2 and year 3.
• Analytic platform (IBox)
Patients will receive IBox testing for surveillance and for-cause. The planned surveillance will occur at months 1, 2, 3, 4, 6, 9, and 12 post-transplant and quarterly in year 2 and year 3.

Locations

Country	Name	City	State
United States	Augusta University	Augusta	Georgia
United States	University of Colorado Hospital	Aurora	Colorado
United States	University of Colorado- Anschutz Medical Campus	Aurora	Colorado
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	SUNY Downstate Medical Center	Brooklyn	New York
United States	Erie County Medical Center	Buffalo	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Metrolina Nephrology Associates	Charlotte	North Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	University of Illinois at Chicago	Chicago	Illinois
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	The University of Missouri	Columbia	Missouri
United States	Ohio State University Medical Center	Columbus	Ohio
United States	UT Southwestern	Dallas	Texas
United States	Geisinger Clinic	Danville	Pennsylvania
United States	Duke University	Durham	North Carolina
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Baylor All Saints Medical Center	Fort Worth	Texas
United States	Texas Research Institute	Fort Worth	Texas
United States	East Carolina University/Vidant Medical Center	Greenville	North Carolina
United States	Houston Methodist Hospital	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of Kentucky Chandler Hospital	Lexington	Kentucky
United States	Saint Barnabus Medical Center	Livingston	New Jersey
United States	Loma Linda Medical Center	Loma Linda	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	University of California, Los Angeles	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	Loyola University	Maywood	Illinois
United States	Methodist Healthcare Foundation	Memphis	Tennessee
United States	University of Miami/Jackson Memorial Hospital	Miami	Florida
United States	University of Minnesota Medical Center	Minneapolis	Minnesota
United States	Intermountain Medical Center	Murray	Utah
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Ochsner Foundation Hospital	New Orleans	Louisiana
United States	Tulane University Medical Center	New Orleans	Louisiana
United States	Integris Baptist Medical Center	Oklahoma City	Oklahoma
United States	The Oklahoma Transplant Center at OU Medical Center	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	AdventHealth	Orlando	Florida
United States	Stanford Health Care	Palo Alto	California
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Virginia Commonwealth University	Richmond	Virginia
United States	UC Davis Medical Center	Sacramento	California
United States	Washington University	Saint Louis	Missouri
United States	Washington University (Barnes Jewish Hospital)	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	UT Health San Antonio	San Antonio	Texas
United States	California Pacific Medical Center	San Francisco	California
United States	University of California San Francisco	San Francisco	California
United States	University of Washington Medical Center	Seattle	Washington
United States	Willis-Knighton Physician Network/ John C. McDonald Regional Transplant Center	Shreveport	Louisiana
United States	Sacred Heart Medical Center	Spokane	Washington
United States	Tampa General Hospital	Tampa	Florida
United States	Baylor Scott & White Medical Center	Temple	Texas
United States	George Washington University	Washington	District of Columbia
United States	Georgetown University	Washington	District of Columbia
United States	Cleveland Clinic - Weston	Weston	Florida
United States	Wake Forest Baptist Medical Center- Department of General Surgery	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
CareDx

Country where clinical trial is conducted

United States, 

References & Publications (2)

Bloom RD, Bromberg JS, Poggio ED, Bunnapradist S, Langone AJ, Sood P, Matas AJ, Mehta S, Mannon RB, Sharfuddin A, Fischbach B, Narayanan M, Jordan SC, Cohen D, Weir MR, Hiller D, Prasad P, Woodward RN, Grskovic M, Sninsky JJ, Yee JP, Brennan DC; Circulating Donor-Derived Cell-Free DNA in Blood for Diagnosing Active Rejection in Kidney Transplant Recipients (DART) Study Investigators. Cell-Free DNA and Active Rejection in Kidney Allografts. J Am Soc Nephrol. 2017 Jul;28(7):2221-2232. doi: 10.1681/ASN.2016091034. Epub 2017 Mar 9. — View Citation

Grskovic M, Hiller DJ, Eubank LA, Sninsky JJ, Christopherson C, Collins JP, Thompson K, Song M, Wang YS, Ross D, Nelles MJ, Yee JP, Wilber JC, Crespo-Leiro MG, Scott SL, Woodward RN. Validation of a Clinical-Grade Assay to Measure Donor-Derived Cell-Free DNA in Solid Organ Transplant Recipients. J Mol Diagn. 2016 Nov;18(6):890-902. doi: 10.1016/j.jmoldx.2016.07.003. Epub 2016 Oct 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Interstitial fibrosis/tubular atrophy (IF/TA) quantified by Banff Working Group biopsy grade(s) at 12 months post-transplant in AlloSure® and renal allograft biopsy managed patients		Feb-2020
Primary	Total number of biopsies planned and performed post-transplant, including both surveillance and clinically indicated biopsies		Feb-2020
Secondary	Transplant glomerulopathy (TG)	Evaluated at one-year post-transplant, quantified by biopsy-based histopathology grade(s)	Dec-2022
Secondary	Patient and graft survival	Evaluated at years 1, 2, and 3 post-transplant	Dec-2022
Secondary	Serum creatinine	Evaluated at years 1, 2, and 3 post-transplant	Dec-2022
Secondary	Estimated glomerular filtration rate	Evaluated at years 1, 2, and 3 post-transplant	Dec-2022
Secondary	Sensitivity of AlloSure for active rejection		Dec-2022
Secondary	Specificity of AlloSure for active rejection		Dec-2022
Secondary	Negative Predictive Value (NPV) of AlloSure for active rejection		Dec-2022
Secondary	Positive Predictive Value (PPV) of AlloSure for active rejection		Dec-2022
Secondary	Develop and validate the clinical use of KidneyCare®		Dec-2022