The PROspera Kidney Transplant ACTIVE Rejection Assessment Registry (ProActive)

Kidney Transplant Rejection Clinical Trial

— ProActive  

Official title:

The PROspera Kidney Transplant ACTIVE Rejection Assessment Registry (ProActive)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04091984
• Other study ID #: 18-039-TRP
• Secondary ID: Pro00037470
• Status: Recruiting
• Start date: November 6, 2019
• Est. completion date: October 1, 2027

Study information

• Verified date: June 2023
• Source: Natera, Inc.
• Contact: Amy Yang, BSN, RN
• Phone: 215.375.4817
• Email: proactiveprosperastudy[@]natera.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5000
• Est. completion date: October 1, 2027
• Est. primary completion date: October 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Kidney Transplant Rejection

Intervention

Diagnostic Test:
• Prospera
No Interventions, this is an observational study.

Locations

Country	Name	City	State
United States	Lehigh Valley Health Network	Allentown	Pennsylvania
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Colorado	Aurora	Colorado
United States	University of Maryland	Baltimore	Maryland
United States	Kidney Care Specialists	Bethlehem	Pennsylvania
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Erie County Medical Center	Buffalo	New York
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	UT Southwestern	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	University of California Davis Medical Center	Davis	California
United States	Harper University Hospital, Detroit Medical Center, Wayne State University	Detroit	Michigan
United States	Henry Ford Health System	Detroit	Michigan
United States	St. John Hospital and Medical Center	Detroit	Michigan
United States	University of Florida	Gainesville	Florida
United States	East Carolina University	Greenville	North Carolina
United States	Hartford Hospital	Hartford	Connecticut
United States	University of California, Irvine	Irvine	California
United States	The University of Kansas Medical Center Research Institute	Kansas City	Kansas
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Keck School of Medicine USC	Los Angeles	California
United States	The Regents of the University of California on behalf of its Los Angeles campus	Los Angeles	California
United States	Northwell Health, Inc	Manhasset	New York
United States	Loyola University Medical Center	Maywood	Illinois
United States	West Virginia University	Morgantown	West Virginia
United States	Vanderbilt University	Nashville	Tennessee
United States	Yale University, School of Medicine	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	University of Nebraska	Omaha	Nebraska
United States	Einstein Medical Center	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Arizona Kidney Disease & Hypertension Centers	Phoenix	Arizona
United States	Legacy Research	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Riverside Community Hospital	Riverside	California
United States	St. Louis University	Saint Louis	Missouri
United States	Washington University School of Medicine in St. Louis	Saint Louis	Missouri
United States	IHC Health Services, Inc	Salt Lake City	Utah
United States	University of Utah	Salt Lake City	Utah
United States	California Institute of Renal Research	San Diego	California
United States	Arizona Kidney Disease & Hypertension Centers	Scottsdale	Arizona
United States	University of Washington	Seattle	Washington
United States	Renal Transplant Associates of New England	Springfield	Massachusetts
United States	Florida Health Sciences Center	Tampa	Florida
United States	Baylor Scott and White Research Institute	Temple	Texas
United States	The University of Toledo	Toledo	Ohio
United States	Arizona Kidney Disease & Hypertension Centers	Tucson	Arizona
United States	Arizona Kidney Disease and Hypertension Centers	Tucson	Arizona
United States	Banner University Medical Center	Tucson	Arizona
United States	The Research Institute at Westchester Medical Center	Valhalla	New York
United States	George Washington University Hospital	Washington	District of Columbia
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	Cleveland Clinic Florida (Weston)	Weston	Florida
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Natera, Inc.	University of Maryland

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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