Evaluation of Patient Outcomes From the Kidney Allograft Outcomes AlloSure Registry (KOAR)

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®.

Study Overview

• Status: Active, not recruiting
• Conditions: Kidney Transplant Rejection
• Intervention / Treatment: Diagnostic test: Donor-derived cell-free DNA (AlloSure®); Other: Standard care; Diagnostic test: Peripheral blood gene expression profiling (AlloMap Kidney); Diagnostic test: Analytic platform (IBox)

Detailed 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.

• Study Type: Observational
• Enrollment (Estimated): 4000

Contacts and Locations

• Study Contact: Name: Sham Dholakia; Phone Number: 415-287-2374; Email: sdholakia@caredx.com
• Study Contact Backup: Name: Alana Burns; Phone Number: 415-287-2420; Email: aburns@caredx.com

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda Medical Center
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
    • Los Angeles, California, United States, 90089
      • University of Southern California
    • Los Angeles, California, United States, 90043
      • Cedars-Sinai Medical Center
    • Palo Alto, California, United States, 94304
      • Stanford Health Care
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • San Francisco, California, United States, 94143
      • University of California San Francisco
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
    • Aurora, Colorado, United States, 80045
      • University of Colorado- Anschutz Medical Campus
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington University
    • Washington, District of Columbia, United States, 20007
      • Georgetown University
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami/Jackson Memorial Hospital
    • Orlando, Florida, United States, 32804
      • AdventHealth
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
    • Weston, Florida, United States, 33331
      • Cleveland Clinic - Weston
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60637
      • University Of Chicago
    • Maywood, Illinois, United States, 60153
      • Loyola University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Chandler Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Medical Center
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Foundation Hospital
    • Shreveport, Louisiana, United States, 71103
      • Willis-Knighton Physician Network/ John C. McDonald Regional Transplant Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02144
      • Massachusetts General Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Columbia, Missouri, United States, 65212
      • The University of Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
    • Saint Louis, Missouri, United States, 63110
      • Washington University (Barnes Jewish Hospital)
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • University of Nebraska Medical Center
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • Saint Barnabus Medical Center
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate Medical Center
    • Buffalo, New York, United States, 14215
      • Erie County Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Metrolina Nephrology Associates
    • Durham, North Carolina, United States, 22705
      • Duke University
    • Greenville, North Carolina, United States, 27834
      • East Carolina University/Vidant Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center- Department of General Surgery
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Integris Baptist Medical Center
    • Oklahoma City, Oklahoma, United States, 73104
      • The Oklahoma Transplant Center at OU Medical Center
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822-4033
      • Geisinger Clinic
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • Methodist Healthcare Foundation
    • Nashville, Tennessee, United States, 37292
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern
    • Fort Worth, Texas, United States, 76104
      • Baylor All Saints Medical Center
    • Fort Worth, Texas, United States, 76104
      • Texas Research Institute
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • San Antonio, Texas, United States, 78229
      • UT Health San Antonio
    • Temple, Texas, United States, 76508
      • Baylor Scott & White Medical Center
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Spokane, Washington, United States, 99204
      • Sacred Heart Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

All eligible renal transplant recipients who meet the inclusion/exclusion criteria will be a part of this observational study.

The control cohort will include the patients cared for without the use of AlloSure® or KidneyCare at the participating centers who received their transplant in the 6 months prior to the enrollment start for the primary cohort.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Primary donor-derived cell-free DNA; 300 patients with planned renal surveillance biopsies at 12 months post-transplantation	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.
Control; A matched control cohort of 1000 patients with planned renal surveillance biopsies at 12 months post-transplantation but were not managed with donor-derived cell-free DNA (AlloSure®) or KidneyCare will be retrospectively selected	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)
Secondary donor-derived cell-free DNA; 1200 patients without planned renal surveillance biopsies at 12 months post-transplantation	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.
Primary KidneyCare®; 300 patients with planned renal surveillance biopsies at 12 months post-transplantation	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.; 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.; Diagnostic test: 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.
Secondary KidneyCare®; 1200 patients without planned renal surveillance biopsies at 12 months post-transplantation	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.; 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.; Diagnostic test: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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
Total number of biopsies planned and performed post-transplant, including both surveillance and clinically indicated biopsies	Feb-2020

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transplant glomerulopathy (TG)	Evaluated at one-year post-transplant, quantified by biopsy-based histopathology grade(s)	Dec-2022
Patient and graft survival	Evaluated at years 1, 2, and 3 post-transplant	Dec-2022
Serum creatinine	Evaluated at years 1, 2, and 3 post-transplant	Dec-2022
Estimated glomerular filtration rate	Evaluated at years 1, 2, and 3 post-transplant	Dec-2022
Sensitivity of AlloSure for active rejection		Dec-2022
Specificity of AlloSure for active rejection		Dec-2022
Negative Predictive Value (NPV) of AlloSure for active rejection		Dec-2022
Positive Predictive Value (PPV) of AlloSure for active rejection		Dec-2022
Develop and validate the clinical use of KidneyCare®		Dec-2022

Collaborators and Investigators

• Sponsor: CareDx

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2018
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: October 24, 2017
• First Submitted That Met QC Criteria: October 25, 2017
• First Posted (Actual): October 30, 2017

Study Record Updates

• Last Update Posted (Actual): June 27, 2023
• Last Update Submitted That Met QC Criteria: June 23, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: KOAR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No