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

NCT05081739 | Withdrawn DMC

• 1 other identifier: 21-053-TRP
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Heart Transplant Failure and Rejection

Outcome Measures

Primary Outcomes (1)

• 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: 1. 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) 2. Graft dysfunction 3. Re-transplantation 4. 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

Study Arms (2)

Prospera Surveillance

EXPERIMENTAL

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

EMB Surveillance

ACTIVE COMPARATOR

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

Interventions

Prospera Transplant Assessment DIAGNOSTIC_TEST

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).

Prospera Surveillance

Endomyocardial biopsy PROCEDURE

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.

EMB Surveillance

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Natera, Inc.: lead

MeSH Terms

Conditions

Rejection, Psychology

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Study Officials

• Michael Olymbios, MD

  Natera, Inc.

  STUDY DIRECTOR

• Palak Shah, MD

  Inova Health Care Services

  PRINCIPAL INVESTIGATOR

• Josef Stehlik, MD

  University of Utah

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2021
• First Posted: October 18, 2021
• Study Start: January 1, 2023
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2026
• Last Updated: April 3, 2024

Record last verified: 2024-04