Clinical trial NCT03326076: Evaluation of Patient Outcomes From the Kidney Allograft Outcomes AlloSure Registry
Official title: Evaluation of Patient Outcomes From the Kidney Allograft Outcomes AlloSure Registry
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Kidney Transplant Rejection
Lead sponsor: CareDx
Sponsor class: INDUSTRY
First posted: 2017-10-30
Enrollment: 4000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief 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®.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Feb-2020
measure: Total number of biopsies planned and performed post-transplant, including both surveillance and clinically indicated biopsies
timeFrame: Feb-2020
Secondary outcomes:
measure: Transplant glomerulopathy (TG)
timeFrame: Dec-2022
measure: Patient and graft survival
timeFrame: Dec-2022
measure: Serum creatinine
timeFrame: Dec-2022
measure: Estimated glomerular filtration rate
timeFrame: Dec-2022
measure: Sensitivity of AlloSure for active rejection
timeFrame: Dec-2022
measure: Specificity of AlloSure for active rejection
timeFrame: Dec-2022
measure: Negative Predictive Value (NPV) of AlloSure for active rejection
timeFrame: Dec-2022
measure: Positive Predictive Value (PPV) of AlloSure for active rejection
timeFrame: Dec-2022
measure: Develop and validate the clinical use of KidneyCare®
timeFrame: Dec-2022
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Loma Linda
country: United States
facility: Loma Linda Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford Health Care
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Aurora
country: United States
facility: University of Colorado- Anschutz Medical Campus
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Washington
country: United States
facility: George Washington University
state: District of Columbia
city: Miami
country: United States
facility: University of Miami/Jackson Memorial Hospital
state: Florida
city: Orlando
country: United States
facility: AdventHealth
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic - Weston
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Maywood
country: United States
facility: Loyola University
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky Chandler Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University Medical Center
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Foundation Hospital
state: Louisiana
city: Shreveport
country: United States
facility: Willis-Knighton Physician Network/ John C. McDonald Regional Transplant Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Columbia
country: United States
facility: The University of Missouri
state: Missouri
city: Saint Louis
country: United States
facility: Washington University (Barnes Jewish Hospital)
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Livingston
country: United States
facility: Saint Barnabus Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: Buffalo
country: United States
facility: Erie County Medical Center
state: New York
city: Charlotte
country: United States
facility: Metrolina Nephrology Associates
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University/Vidant Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center- Department of General Surgery
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: The Oklahoma Transplant Center at OU Medical Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: Integris Baptist Medical Center
state: Oklahoma
city: Danville
country: United States
facility: Geisinger Clinic
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: Methodist Healthcare Foundation
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern
state: Texas
city: Fort Worth
country: United States
facility: Baylor All Saints Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Research Institute
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: San Antonio
country: United States
facility: UT Health San Antonio
state: Texas
city: Temple
country: United States
facility: Baylor Scott & White Medical Center
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Spokane
country: United States
facility: Sacred Heart Medical Center
state: Washington
Study officials:
References:
citation: 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.
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.