Donor-Derived Cell-free DNA to DETect REjection in Cardiac Transplantation (DETECT)

The study objective is to demonstrate that rejection surveillance of heart transplant recipients with Prospera dd-cfDNA is non-inferior to rejection surveillance with endomyocardial biopsy and histology in the first post-transplant year.

Study Overview

• Status: Withdrawn
• Conditions: Heart Transplant Failure and Rejection
• Intervention / Treatment: Diagnostic test: Prospera Transplant Assessment; Procedure: Endomyocardial biopsy

Detailed Description

Subjects will be enrolled into the study while on the transplant waiting list prior to heart transplantation. All subjects will follow the center's standard of care surveillance schedule from transplant through 4 weeks post-transplantation. EMB during this phase is expected to occur roughly weekly.

Subjects will be randomized in a 1:1 ratio 30 days (± 7 days) post-transplant to Prospera surveillance (Study Group) versus EMB surveillance (Control Group, standard clinical care). Rejection surveillance (Prospera testing in the Study Group and EMB in the Control Group) will be performed at times corresponding to the institutional standard of care schedule for rejection surveillance.

Study Group: Prospera Surveillance (300 Subjects) Subjects will undergo Prospera testing at times corresponding to the institution's graft surveillance schedule. Prospera test results will be provided to the clinical team. Prospera cfDNA level < 0.15% will be interpreted as negative and a surveillance EMB will be omitted. Prospera cfDNA ≥ 0.15% will be followed by EMB. A for-cause EMB can be done per the clinical team's discretion at any time.

Control Group: EMB Surveillance (standard of care) (300 Subjects) Subjects will undergo surveillance EMB per the institution's standard clinical care.

The study intervention will be during the first 12 months post-transplant.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Male or female, age 18 years or older at the time of signing informed consent.
2. On the heart transplant waiting list and expected to receive a heart transplant.
3. Able to read, understand and provide written informed consent.
4. Able and willing to comply with the study visit schedule, study procedures and study requirements.

Exclusion Criteria:

1. Heart transplantation has been performed.
2. Concurrent multiple solid organ or tissue transplant
3. Prior history of any organ or cellular transplantation.
4. Planned use of other commercially available or investigational cfDNA or gene expression profile assays.
5. Pregnant.
6. Hemodynamically unstable or other serious medical condition that may adversely affect the subject's ability to participate in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prospera Surveillance; Subjects will undergo Prospera testing in accordance with the institution's Control Group EMB surveillance standard of care schedule, which is expected to be approximately every other week months 2 and 3, then monthly through months 4 through 6, then every 1-3 months during months 7 through 12. Prospera test results will be provided to investigators. Prospera cfDNA level < 0.15 % will be interpreted as negative, and screening EMB will be omitted. EMB will be performed for cfDNA level ≥ 0.15 %. At any time, the clinical team may perform for cause EMB for standard clinical indications (e.g., evidence of graft failure) as per the treating team's discretion.	Diagnostic test: Prospera Transplant Assessment; Prospera™ detects allograft rejection noninvasively and with high accuracy by measuring the fraction of dd-cfDNA in the patient's blood, without the need for prior donor or recipient genotyping. Prospera is a commercially available LDT developed by Natera, Inc. Natera is a laboratory certified under the Clinical Laboratory Improvement Amendments (CLIA).
Active Comparator: EMB Surveillance; Subjects will undergo surveillance EMB per the institution's standard clinical care, which is expected to be approximately every other week months 2 and 3, then monthly through months 4 through 6, then every 1-3 months during months 7 through 12. At any time, the clinical team may perform for cause EMB for standard clinical indications (e.g., evidence of graft failure) as per the treating team's discretion.	Procedure: Endomyocardial biopsy; Subjects will undergo surveillance EMB per the institution's standard clinical care, which is expected to be approximately every other week in months 2 and 3, then monthly through month 6, then every 1-3 months through the end of month 12.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Demonstrate the use of Prospera for post-transplant surveillance is non-inferior to the current standard of care, EMB surveillance, with respect to the primary composite endpoint.	The primary endpoint of the study is a composite endpoint defined as the first occurrence of one or more of the following events after transplant: Treated rejection with or without graft dysfunction and/or graft dysfunction requiring treatment with pulse dose steroids, monoclonal antibodies, plasmapheresis, and/or intravenous immunoglobulin (IVIg); Graft dysfunction; Re-transplantation; Death Clinical endpoints are defined as follows: Rejection: ISHLT ACR Grade ≥ 2R or AMR Grade ≥ pAMR1; Graft dysfunction: LVEF decline >10% from baseline and < 50% absolute LVEF by echocardiography; Re-transplantation: being listed for re-transplant or being re-transplanted	12 months

Collaborators and Investigators

• Sponsor: Natera, Inc.
• Investigators: Study Director: Michael Olymbios, MD, Natera, Inc.; Principal Investigator: Palak Shah, MD, Inova Health Care Services; Study Chair: Josef Stehlik, MD, University of Utah

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2023
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: September 17, 2021
• First Submitted That Met QC Criteria: October 13, 2021
• First Posted (Actual): October 18, 2021

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 21-053-TRP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No