A Comparative Effectiveness Study in Heart Transplant Patients of Rejection Surveillance With Cell-free DNA Versus Endomyocardial Biopsy

NCT06414603 | Active Not Recruiting DMC

• 1 other identifier: 23-069-TRP
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 16

Brief Summary

This is an open label Comparative Effectiveness Research (CER) study in which patients will be randomized at the site level to Prospera surveillance or EMB surveillance in a 2:1 ratio (Prospera to EMB) at each site. Subjects will be enrolled into the study while under evaluation for heart transplantation or 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 or bi-weekly. Study group assignment will take place at randomization. Subjects will be randomized 30 days (± 10 days) post-transplant to Prospera surveillance versus EMB surveillance in a 2:1 ratio. Rejection surveillance (Prospera Group and EMB Group) will be performed at times corresponding to the institutional standard of care schedule for rejection surveillance.

Conditions

Heart Transplant Failure and Rejection

Keywords

Heart Transplant

Outcome Measures

Primary Outcomes (1)

• Primary Clinical Endpoint

  Incidence of the composite endpoint defined as the first occurrence of treated rejection with graft dysfunction\*, treated rejection without graft dysfunction, graft dysfunction, retransplantation, and/or death. Clinical endpoints are defined as follows: 1. Rejection: ISHLT ACR Grade ≥ 2R or AMR Grade ≥ pAMR1 2. Graft dysfunction: LVEF decline ≥ 10% from baseline and \< 50% absolute LVEF by echocardiography 3. Retransplantation: being listed for re-transplant or being re-transplanted * Treated rejection with graft dysfunction and/or graft dysfunction requiring treatment with pulse dose steroids, monoclonal antibodies, plasmapheresis, and/or intravenous immunoglobulin (IVIg).

  12 months

Study Arms (2)

Prospera Surveillance Cohort

EXPERIMENTAL

Subjects are required to 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 low risk for acute rejection (AR). Prospera cfDNA ≥ 0.15% will be interpreted as increased risk for AR and may be followed by EMB to rule out AR at the discretion of the treating clinicians. All other standard of care modalities for assessing AR can be used at the discretion of the treating clinicians at any time throughout the study. As per standard of care, in subjects with clinical signs or symptoms of rejection, a for cause EMB can be done per the clinical team's discretion at any time during the study.

Diagnostic Test: The Prospera™ Test

Endomyocardial Biopsy Surveillance Cohort

NO INTERVENTION

Subjects will undergo surveillance EMB per the institution's standard clinical care. Biopsy interpretation will be per the institutional pathologist using international guidelines for grading of acute cellular or antibody-mediated rejection. Subjects will also have Prospera testing performed at the time of surveillance EMB for the purpose of measuring concordance between dd-cfDNA surveillance testing and surveillance EMB; Prospera results will not be returned to investigators for subjects in the EMB surveillance group.

Interventions

The Prospera™ Test DIAGNOSTIC_TEST

The Prospera™ test is a non-invasive test intended to detect and quantify the fraction of donor-derived cell-free DNA (dd-cfDNA) to supplement management and surveillance of allograft rejection in patients who have undergone organ transplantation. It employs Next Generation Sequencing (NGS), which is performed on cell-free DNA (cfDNA) that is extracted from the patient's plasma to discriminate between the patient's DNA and the solid organ-allograft DNA. In study 23-069-TRP, the Prospera test is indicated for heart allograft rejection surveillance in lieu of surveillance endomyocardial biopsy. Prospera results should be considered together with clinical evaluations and other diagnostic testing or imaging results. Prospera will be run as a centralized laboratory developed test that is developed and validated under Design Controls. The test will be run within Natera's CLIA-certified and CAP-accredited laboratory.

Prospera Surveillance Cohort

Eligibility Criteria

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

You may qualify if:

• Age 18 years or older at the time of signing informed consent.
• Undergoing transplant evaluation or currently on the heart transplant waiting list and expected to receive a heart transplant.
• Able to read, understand and provide written informed consent. If the patient is unable to sign informed consent, a legally authorized representative (LAR) can consent on behalf of the patient.
• Able and willing to comply with the study visit schedule, study procedures and study requirements.

You may not qualify if:

• Concurrent multiple solid organ or tissue transplants.
• Prior history of any organ or cellular transplantation.
• Planned use of other commercially available or investigational cfDNA or gene expression profile assays for rejection surveillance.
• 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

Study Sites (16)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of California, San Diego

San Diego, California, 92103, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

AdventHealth Orlando

Orlando, Florida, 32804, United States

Location

Kansas University Medical Center

Kansas City, Kansas, 66160, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Texas, Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Baylor Scott White - Temple

Temple, Texas, 76508, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Inova Schar Heart and Vascular Institute

Falls Church, Virginia, 22042, United States

Location

Related Publications (1)

• Kim H, Cusi V, McLenon M, Rodriguez JBC, Bui QM, Chak J, Urey MA, Cole J, Fielding-Miller R, Kim PJ. Perspectives of Heart Transplant Patients and Providers on Acute Rejection Surveillance: A Mixed-Methods Study. Clin Transplant. 2026 Jan;40(1):e70438. doi: 10.1111/ctr.70438.

  PMID: 41492943 DERIVED

MeSH Terms

Conditions

Rejection, Psychology

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Study Officials

• Michael Olymbios, MD

  Natera, Inc.

  STUDY DIRECTOR

• Josef Stehlik, MD

  University of Utah

  STUDY CHAIR

• Palak Shah, MD

  Inova Schar Heart and Vascular

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2024
• First Posted: May 16, 2024
• Study Start: June 10, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

US (16)