Clinical trial NCT04091984: The PROspera Kidney Transplant ACTIVE Rejection Assessment Registry (ProActive)
Official title: The PROspera Kidney Transplant ACTIVE Rejection Assessment Registry (ProActive)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Kidney Transplant Rejection
Keywords: donor-derived cfDNA
Lead sponsor: Natera, Inc.
Sponsor class: INDUSTRY
Collaborators: name: University of Maryland
First posted: 2019-09-17
Enrollment: 5000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Approximately 5,000 adult renal allograft participants will be enrolled in this study, and data will be collected from a de-identified cohort of approximately 500 historical control patients who had a renal allograft.

Brief summary: The ProActive registry is a longitudinal, multi-center study with a prospective arm observing clinical care for patients receiving physician ordered Prospera, an allograft rejection test, and a historical control arm collecting data on cases at the same sites whose kidney allograft rejection status was managed with Serum Creatinine SCr/estimated Glomerular Filtration Rate eGFR. This registry will compare patient management and outcomes in patients who receive Prospera (Prospera arm) to the outcomes of the historical control group (control arm) to determine Prospera's clinical utility. High-risk subjects defined as having a biopsy-demonstrated rejection event or at least one pre-existing Donor Specific Antibody DSA with total Mean Fluorescent Intensity MFI\>3000 or a calculated Panel Reactive Antibodies cPRA\>70% will be followed for an additional period up to 24 months in both the Prospera arm and historical control arm.

Detailed description: The primary objective is to differentiate the clinical utility of Prospera testing from the use of creatinine testing as measured by the proportion of positive biopsies in post renal allograft patients.

Secondary objectives include:

* To observe the performance of the Prospera assay in detecting AR (repeated validation)
* To evaluate whether Prospera can detect AR earlier and more often than SCr
* To determine whether use of Prospera will significant decrease the rate of overall number of biopsies when compared to the rate of biopsies in the control arm

Eligibility criteria: Inclusion Criteria Prospera Arm:

1. 18 years of age or older
2. Renal allograft (kidney transplant) up to 2 years prior to signing informed consent. Newly transplanted patients to receive Prospera testing within 60 days of transplant
3. A genetically different donor (not an identical twin)
4. Selected by a healthcare provider to receive Prospera dd-cfDNA test according to the regular interval testing schedule as part of their practical care
5. Able to read, understand and provide written informed consent
6. Willing and able to comply with the study visit schedule and study requirements

Exclusion Criteria Prospera Arm:

1. Pregnant
2. Routine ongoing testing with another dd-cfDNA or RNA biomarker test after enrollment into the ProActive study. Receipt of another dd-cfDNA test within 30 days of a patient being enrolled in the study.
3. History of another organ transplant (i.e. aside from renal allograph)
4. A serious medical condition that may adversely affect ability to participate in the study (e.g, dementia, current diagnosis of cancer)
5. Previously enrolled in the ProActive Registry, with the exception of a graft failure and a new renal allograft

Inclusion Criteria Control Arm:

1. 18 years of age or older at the time of transplant
2. Had a renal allograft
3. Had a genetically different donor
4. Had a minimum of three evaluations per year during the three years since the renal allograft or until allograft failure

Exclusion Criteria Control Arm:

1. Female patients who were pregnant at any time during the 3-year historical control data collection period
2. Had a transplanted organ other than kidney
3. Received results from a dd-cfDNA test designed to assess renal allograft rejection during the historical control data collection period

Primary outcomes:
measure: Efficiency of biopsies
timeFrame: 3 years
measure: Graft function
timeFrame: 3 years
Secondary outcomes:
measure: Evaluate the performance of Prospera
timeFrame: 5 years
measure: Evaluate whether Prospera can detect acute rejection earlier than serum creatinine
timeFrame: 3 years
measure: Determine if and how Prospera testing impacts patient care
timeFrame: 5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Arizona Kidney Disease & Hypertension Centers
state: Arizona
city: Scottsdale
country: United States
facility: Arizona Kidney Disease & Hypertension Centers
state: Arizona
city: Tucson
country: United States
facility: Arizona Kidney Disease and Hypertension Centers
state: Arizona
city: Tucson
country: United States
facility: Arizona Kidney Disease & Hypertension Centers
state: Arizona
city: Tucson
country: United States
facility: Banner University Medical Center
state: Arizona
city: Davis
country: United States
facility: University of California Davis Medical Center
state: California
city: Irvine
country: United States
facility: University of California, Irvine
state: California
city: Los Angeles
country: United States
facility: Keck School of Medicine USC
state: California
city: Los Angeles
country: United States
facility: The Regents of the University of California on behalf of its Los Angeles campus
state: California
city: Riverside
country: United States
facility: Riverside Community Hospital
state: California
city: San Diego
country: United States
facility: California Institute of Renal Research
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: New Haven
country: United States
facility: Yale University, School of Medicine
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Tampa
country: United States
facility: Florida Health Sciences Center
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida (Weston)
state: Florida
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Kansas City
country: United States
facility: The University of Kansas Medical Center Research Institute
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Hospital and Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: Renal Transplant Associates of New England
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Harper University Hospital, Detroit Medical Center, Wayne State University
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Saint Louis
country: United States
facility: St. Louis University
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska
state: Nebraska
city: Las Vegas
country: United States
facility: University Medical Center of Southern Nevada
state: Nevada
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Erie County Medical Center
state: New York
city: Manhasset
country: United States
facility: Northwell Health, Inc
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Valhalla
country: United States
facility: The Research Institute at Westchester Medical Center
state: New York
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Toledo
country: United States
facility: The University of Toledo
state: Ohio
city: Portland
country: United States
facility: Legacy Research
state: Oregon
city: Allentown
country: United States
facility: Lehigh Valley Health Network
state: Pennsylvania
city: Bethlehem
country: United States
facility: Kidney Care Specialists
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Einstein Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern
state: Texas
city: Temple
country: United States
facility: Baylor Scott and White Research Institute
state: Texas
city: Salt Lake City
country: United States
facility: IHC Health Services, Inc
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
Study officials:
affiliation: University of Maryland
name: Jonathan Bromberg, MD
role: PRINCIPAL_INVESTIGATOR
References: