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

NCT ID: NCT05081739

Last Updated: 2024-04-03

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-31
• Study Completion Date: 2026-01-31

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.

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.

Conditions

Heart Transplant Failure and Rejection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Prospera Transplant Assessment

Intervention Type: 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).

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.

Group Type: ACTIVE_COMPARATOR

Endomyocardial biopsy

Intervention Type: 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.

Interventions

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).

Intervention Type: DIAGNOSTIC_TEST

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.

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Natera, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Olymbios, MD

Role: STUDY_DIRECTOR

Natera, Inc.

Palak Shah, MD

Role: PRINCIPAL_INVESTIGATOR

Inova Health Care Services

Josef Stehlik, MD

Role: STUDY_CHAIR

University of Utah

Other Identifiers

21-053-TRP

Identifier Type: -

Identifier Source: org_study_id