The PROspera Kidney Transplant ACTIVE Rejection Assessment Registry (ProActive) (ProActive)

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.

Study Overview

• Status: Recruiting
• Conditions: Kidney Transplant Rejection
• Intervention / Treatment: Diagnostic test: Prospera

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

• Study Type: Observational
• Enrollment (Estimated): 5000

Contacts and Locations

• Study Contact: Name: Amy Yang, BSN, RN; Phone Number: 215.375.4817; Email: proactiveprosperastudy@natera.com

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • University of Alabama at Birmingham
      • Contact: Shikha Mehta, MD
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Recruiting
      • Arizona Kidney Disease & Hypertension Centers
      • Principal Investigator: Alexander Nimri, MD
    • Scottsdale, Arizona, United States, 85258
      • Recruiting
      • Arizona Kidney Disease & Hypertension Centers
      • Principal Investigator: Romanita Nica, MD
    • Tucson, Arizona, United States, 85719
      • Recruiting
      • Banner University Medical Center
      • Principal Investigator: Venkatesh Ariyamuthu
    • Tucson, Arizona, United States, 85712
      • Recruiting
      • Arizona Kidney Disease and Hypertension Centers
      • Principal Investigator: David Whittman, MD
    • Tucson, Arizona, United States, 85718
      • Recruiting
      • Arizona Kidney Disease & Hypertension Centers
      • Principal Investigator: David Whittman, MD
  • California
    • Davis, California, United States, 95616
      • Recruiting
      • University of California Davis Medical Center
      • Contact: Muna Alnimri, MD
    • Irvine, California, United States, 92697
      • Recruiting
      • University of California, Irvine
      • Contact: Ekamol Tantisattamo, MD
    • Los Angeles, California, United States, 90033
      • Recruiting
      • Keck School of Medicine USC
      • Contact: Yasir Qazi, MD
    • Los Angeles, California, United States, 90095
      • Recruiting
      • The Regents of the University of California on behalf of its Los Angeles campus
      • Contact: Suphamai Bunnapradist, MD
    • Riverside, California, United States, 92501
      • Recruiting
      • Riverside Community Hospital
      • Contact: Alagappan Annamalai, M.D.
    • San Diego, California, United States, 92123
      • Recruiting
      • California Institute of Renal Research
      • Contact: Arman Faravardeh, MD
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado
      • Principal Investigator: Erik Stites, MD
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Recruiting
      • Hartford Hospital
      • Contact: Joseph Tremaglio, MD
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale University, School of Medicine
      • Principal Investigator: Madhav Menon, MD
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • Withdrawn
      • George Washington University Hospital
    • Washington, District of Columbia, United States, 20057
      • Recruiting
      • Georgetown University Medical Center
      • Contact: Matthew Cooper, MD
  • Florida
    • Gainesville, Florida, United States, 32611
      • Recruiting
      • University of Florida
      • Contact: Ali Zarrinpar, MD
    • Tampa, Florida, United States, 33606
      • Recruiting
      • Florida Health Sciences Center
      • Contact: Martin Aldana Campos, MD
    • Weston, Florida, United States, 33331
      • Recruiting
      • Cleveland Clinic Florida (Weston)
      • Principal Investigator: Neerja Agrawal
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Recruiting
      • Loyola University Medical Center
      • Contact: Sanjeev Akkina, MD
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • The University of Kansas Medical Center Research Institute
      • Contact: Mallika Gupta, MD
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland
      • Contact: Jonathan Bromberg, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Anil Chandraker, MD
    • Burlington, Massachusetts, United States, 01805
      • Recruiting
      • Lahey Hospital and Medical Center
      • Principal Investigator: Edward Walshe, MD
    • Springfield, Massachusetts, United States, 01107
      • Recruiting
      • Renal Transplant Associates of New England
      • Principal Investigator: Michael Germain, MD
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Principal Investigator: Silas P. Norman, MD, MPH
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Health System
      • Contact: Milagros D Samaniego-Picota, MD
    • Detroit, Michigan, United States, 48201
      • Terminated
      • Harper University Hospital, Detroit Medical Center, Wayne State University
    • Detroit, Michigan, United States, 48236
      • Withdrawn
      • St. John Hospital and Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine in St. Louis
      • Contact: Tarek Alhamad, MD
    • Saint Louis, Missouri, United States, 63103
      • Recruiting
      • St. Louis University
      • Contact: Henry Randall, MD
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Recruiting
      • University of Nebraska
      • Principal Investigator: Scott Westphal, MD
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Recruiting
      • University Medical Center of Southern Nevada
      • Contact: Ayoola Adekile, MD
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • Recruiting
      • Saint Barnabas Medical Center
      • Contact: Anup Patel, MD
  • New York
    • Buffalo, New York, United States, 14215
      • Recruiting
      • Erie County Medical Center
      • Contact: Liise Kayler, MD
    • Manhasset, New York, United States, 11030
      • Recruiting
      • Northwell Health, Inc
      • Contact: Lewis Teperman, MD
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
      • Contact: Geoffrey Dube, MD
    • Valhalla, New York, United States, 10595
      • Recruiting
      • The Research Institute at Westchester Medical Center
      • Contact: Daniel Glicklich, MD
  • North Carolina
    • Greenville, North Carolina, United States, 27858
      • Recruiting
      • East Carolina University
      • Contact: David Leeser, MD
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Wake Forest University Health Sciences
      • Contact: Robert J Stratta, MD
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • The Cleveland Clinic Foundation
      • Contact: Richard Fatica, MD
    • Toledo, Ohio, United States, 43606
      • Recruiting
      • The University of Toledo
      • Contact: Obinna Ekwenna, MD
  • Oregon
    • Portland, Oregon, United States, 97232
      • Recruiting
      • Legacy Research
      • Contact: William Bennett, MD
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Recruiting
      • Lehigh Valley Health Network
      • Contact: Michael Moritz, MD
    • Bethlehem, Pennsylvania, United States, 18017
      • Recruiting
      • Kidney Care Specialists
      • Principal Investigator: Nelson Kopyt, MD
    • Danville, Pennsylvania, United States, 17822
      • Withdrawn
      • Geisinger Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Principal Investigator: Ty Dunn, MD
    • Philadelphia, Pennsylvania, United States, 19141
      • Recruiting
      • Einstein Medical Center
      • Principal Investigator: Gitana Bradauskaite, MD
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • Rhode Island Hospital
      • Principal Investigator: Basma Merhi, MD
      • Contact: Basma Merhi, MD
  • Tennessee
    • Nashville, Tennessee, United States, 37235
      • Recruiting
      • Vanderbilt University
      • Contact: Anthony Langone, MD
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • UT Southwestern
      • Contact: David Wojciechowski, MD
    • Temple, Texas, United States, 76508
      • Terminated
      • Baylor Scott and White Research Institute
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Recruiting
      • University of Utah
      • Contact: Fuad Shihab, MD
    • Salt Lake City, Utah, United States, 84111
      • Recruiting
      • IHC Health Services, Inc
      • Contact: Sanjiv Anand, MD
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Recruiting
      • Virginia Commonwealth University
      • Contact: Layla Kamal, MD
  • Washington
    • Seattle, Washington, United States, 98195
      • Recruiting
      • University of Washington
      • Contact: Nicolae Leca, MD
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Recruiting
      • West Virginia University
      • Principal Investigator: Dinesh Kannabhiran, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Prospera Arm; There is no intervention in this study. Adult patients who have received a kidney allograft from a genetically different donor in the past 2 years including within 60 days and who have been selected by their healthcare provider to receive Prospera dd-cfDNA testing according to their regular interval testing schedule as part of their clinical care will have medical records pertaining to their kidney rejection status collected at each study visit.	Diagnostic test: Prospera; No Interventions, this is an observational study.
Control Arm; The control arm will consist of retrospective data review of cases where a renal allograft from a genetically different donor was performed. Data pertaining to to their kidney rejection status from a minimum of 3 time points per year post allograft (up to 5 years) or until renal allograft failure will be collected.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficiency of biopsies	The proportion of clinically indicated biopsies that show Active Rejection (AR) will be measured in the Prospera arm and the control arm. Specifically, the proportion of clinically indicated biopsies showing AR in individuals with a positive donor derived-cell free DNA dd-cfDNA test at the time of Bx in the test arm, where Prospera has been integrated into the care paradigm, will be compared against the proportion of clinically indicated biopsies showing AR in the control arm.	3 years
Graft function	Graft function in the Prospera arm and control arm will be measured. This will be assessed by examining the average eGFR score (as calculated using serum creatinine Chronic Kidney Disease-EPIdemiology collaboration CKD_EPI equation) at year three in the Prospera arm compared to the average eGFR score determined at year three in the historical control arm.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the performance of Prospera	The performance of Prospera to detect AR will be evaluated. The sensitivity, specificity, Positive & Negative Predictive Value of the assay in sub-cohorts of patients will be calculated and compared to the performance of serum creatinine to detect AR in those cohorts.	5 years
Evaluate whether Prospera can detect acute rejection earlier than serum creatinine	The grade of rejection observed in biopsies in the Prospera arm will be compared to the historical control arm which used serum creatinine.	3 years
Determine if and how Prospera testing impacts patient care	The proportion of Prospera assay results that doctors felt influenced their decisions around management of patients and biopsies will be calculated. This will be analyzed separately for the for-cause and protocol biopsies.	5 years

Collaborators and Investigators

• Sponsor: Natera, Inc.
• Collaborators: University of Maryland
• Investigators: Principal Investigator: Jonathan Bromberg, MD, University of Maryland

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2019
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: September 6, 2019
• First Submitted That Met QC Criteria: September 13, 2019
• First Posted (Actual): September 17, 2019

Study Record Updates

• Last Update Posted (Actual): June 12, 2023
• Last Update Submitted That Met QC Criteria: June 8, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: donor-derived cfDNA
• Other Study ID Numbers: 18-039-TRP; Pro00037470 (Other Identifier: Advarra IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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