The PROspera Kidney Transplant ACTIVE Rejection Assessment Registry (ProActive)

Sponsor

Natera, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04091984

Collaborator

University of Maryland (Other)

5,000

Enrollment

Locations

94.8

Anticipated Duration (Months)

89.3

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplant Rejection	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 Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

5000 participants

Observational Model:

Case-Control

Time Perspective:

Other

Official Title:

The PROspera Kidney Transplant ACTIVE Rejection Assessment Registry (ProActive)

Actual Study Start Date :

Nov 6, 2019

Anticipated Primary Completion Date :

Oct 1, 2026

Anticipated Study Completion Date :

Oct 1, 2027

Arms and Interventions

Arm	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.

Arm

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.

Outcome Measures

Primary Outcome Measures

Efficiency of biopsies [3 years]
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.
Graft function [3 years]
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.

Secondary Outcome Measures

Evaluate the performance of Prospera [5 years]
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.
Evaluate whether Prospera can detect acute rejection earlier than serum creatinine [3 years]
The grade of rejection observed in biopsies in the Prospera arm will be compared to the historical control arm which used serum creatinine.
Determine if and how Prospera testing impacts patient care [5 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria Prospera Arm:

18 years of age or older
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
A genetically different donor (not an identical twin)
Selected by a healthcare provider to receive Prospera dd-cfDNA test according to the regular interval testing schedule as part of their practical care
Able to read, understand and provide written informed consent
Willing and able to comply with the study visit schedule and study requirements

Exclusion Criteria Prospera Arm:

Pregnant
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.
History of another organ transplant (i.e. aside from renal allograph)
A serious medical condition that may adversely affect ability to participate in the study (e.g, dementia, current diagnosis of cancer)
Previously enrolled in the ProActive Registry, with the exception of a graft failure and a new renal allograft

Inclusion Criteria Control Arm:

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

Exclusion Criteria Control Arm:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Arizona Kidney Disease & Hypertension Centers	Phoenix	Arizona	United States	85016
3	Arizona Kidney Disease & Hypertension Centers	Scottsdale	Arizona	United States	85258
4	Arizona Kidney Disease and Hypertension Centers	Tucson	Arizona	United States	85712
5	Arizona Kidney Disease & Hypertension Centers	Tucson	Arizona	United States	85718
6	Banner University Medical Center	Tucson	Arizona	United States	85719
7	University of California Davis Medical Center	Davis	California	United States	95616
8	University of California, Irvine	Irvine	California	United States	92697
9	Keck School of Medicine USC	Los Angeles	California	United States	90033
10	The Regents of the University of California on behalf of its Los Angeles campus	Los Angeles	California	United States	90095
11	California Institute of Renal Research	San Diego	California	United States	92123
12	University of Colorado	Aurora	Colorado	United States	80045
13	Hartford Hospital	Hartford	Connecticut	United States	06102
14	Yale University, School of Medicine	New Haven	Connecticut	United States	06520
15	George Washington University Hospital	Washington	District of Columbia	United States	20037
16	Georgetown University Medical Center	Washington	District of Columbia	United States	20057
17	University of Florida	Gainesville	Florida	United States	32611
18	Florida Health Sciences Center	Tampa	Florida	United States	33606
19	Cleveland Clinic Florida (Weston)	Weston	Florida	United States	33331
20	Loyola University Medical Center	Maywood	Illinois	United States	60153
21	The University of Kansas Medical Center Research Institute	Kansas City	Kansas	United States	66160
22	University of Maryland	Baltimore	Maryland	United States	21201
23	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
24	Lahey Hospital and Medical Center	Burlington	Massachusetts	United States	01805
25	Renal Transplant Associates of New England	Springfield	Massachusetts	United States	01107
26	University of Michigan	Ann Arbor	Michigan	United States	48109
27	Harper University Hospital, Detroit Medical Center, Wayne State University	Detroit	Michigan	United States	48201
28	Henry Ford Health System	Detroit	Michigan	United States	48202
29	St. John Hospital and Medical Center	Detroit	Michigan	United States	48236
30	St. Louis University	Saint Louis	Missouri	United States	63103
31	Washington University School of Medicine in St. Louis	Saint Louis	Missouri	United States	63110
32	University of Nebraska	Omaha	Nebraska	United States	68198
33	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
34	Saint Barnabas Medical Center	Livingston	New Jersey	United States	07039
35	Erie County Medical Center	Buffalo	New York	United States	14215
36	Northwell Health, Inc	Manhasset	New York	United States	11030
37	Columbia University Medical Center	New York	New York	United States	10032
38	The Research Institute at Westchester Medical Center	Valhalla	New York	United States	10595
39	East Carolina University	Greenville	North Carolina	United States	27858
40	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
41	The Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
42	The University of Toledo	Toledo	Ohio	United States	43606
43	Legacy Research	Portland	Oregon	United States	97232
44	Lehigh Valley Health Network	Allentown	Pennsylvania	United States	18103
45	Kidney Care Specialists	Bethlehem	Pennsylvania	United States	18017
46	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
47	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
48	Einstein Medical Center	Philadelphia	Pennsylvania	United States	19141
49	Vanderbilt University	Nashville	Tennessee	United States	37235
50	UT Southwestern	Dallas	Texas	United States	75390
51	Baylor Scott and White Research Institute	Temple	Texas	United States	76508
52	IHC Health Services, Inc	Salt Lake City	Utah	United States	84111
53	University of Utah	Salt Lake City	Utah	United States	84132
54	Virginia Commonwealth University	Richmond	Virginia	United States	23298
55	University of Washington	Seattle	Washington	United States	98195
56	West Virginia University	Morgantown	West Virginia	United States	26506

Sponsors and Collaborators

Natera, Inc.
University of Maryland

Investigators

Principal Investigator: Jonathan Bromberg, MD, University of Maryland

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Natera, Inc.

ClinicalTrials.gov Identifier:

NCT04091984

Other Study ID Numbers:

18-039-TRP
Pro00037470

First Posted:

Sep 17, 2019

Last Update Posted:

Aug 10, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Natera, Inc.

donor-derived cfDNA

Study Results

No Results Posted as of Aug 10, 2022