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

NCT ID: NCT06414603

Last Updated: 2025-04-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

250 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-06-10

Study Completion Date

2025-12-31

Brief Summary

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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.

Detailed Description

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All subjects will undergo standard of care assessments for rejection monitoring in addition to Prospera testing and/or EMB in accordance with each site's clinical care protocols and at the discretion of the treating clinician. Quality of life questionnaires will be completed at week 4, month 6 and month 12 post-transplant.

Study Group: Prospera (dd-cfDNA) Surveillance Group 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.

Control Group: EMB Surveillance Group 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.

Subjects in both the Prospera and EMB Surveillance Groups will have Prospera blood draws performed at the time of any for cause EMB. Results of Prospera testing performed in conjunction with for cause EMB will not be returned to investigators or subjects.

Blood samples for exploratory mechanistic endpoints (miRNA) will be obtained at the time of each Prospera or EMB surveillance visit and at the time of any for cause EMB.

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

Conditions

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Heart Transplant Failure and Rejection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Endomyocardial Biopsy Surveillance Cohort

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Prospera Surveillance Cohort

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.

Group Type EXPERIMENTAL

The Prospera™ Test

Intervention Type 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.

Interventions

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The Prospera™ 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.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

1. Age 18 years or older at the time of signing informed consent.
2. Undergoing transplant evaluation or currently on the heart transplant waiting list and expected to receive a heart transplant.
3. 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.
4. Able and willing to comply with the study visit schedule, study procedures and study requirements.

Exclusion Criteria

1. Concurrent multiple solid organ or tissue transplants.
2. Prior history of any organ or cellular transplantation.
3. Planned use of other commercially available or investigational cfDNA or gene expression profile assays for rejection surveillance.
4. Pregnant.
5. 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

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Natera, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael Olymbios, MD

Role: STUDY_DIRECTOR

Natera, Inc.

Josef Stehlik, MD

Role: STUDY_CHAIR

University of Utah

Palak Shah, MD

Role: STUDY_CHAIR

Inova Schar Heart and Vascular

Locations

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Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status NOT_YET_RECRUITING

University of California, San Diego

San Diego, California, United States

Site Status RECRUITING

University of Colorado

Aurora, Colorado, United States

Site Status RECRUITING

Mayo Clinic

Jacksonville, Florida, United States

Site Status RECRUITING

Piedmont Healthcare

Atlanta, Georgia, United States

Site Status NOT_YET_RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

Site Status RECRUITING

Duke University

Durham, North Carolina, United States

Site Status RECRUITING

University of Texas, Southwestern Medical Center

Dallas, Texas, United States

Site Status RECRUITING

University of Utah

Salt Lake City, Utah, United States

Site Status RECRUITING

Inova Schar Heart and Vascular Institute

Falls Church, Virginia, United States

Site Status NOT_YET_RECRUITING

Countries

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United States

Central Contacts

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Kiara Stoddard

Role: CONTACT

(650) 249-9090

Facility Contacts

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Lucy Garcia

Role: primary

Taylor Tran

Role: primary

Laura Peters

Role: primary

Jessica Toukmehji

Role: primary

Caryn Bernstein

Role: primary

Ellen Ren

Role: primary

Kelly Schaffer

Role: primary

Lacey Taylor

Role: primary

Adam DeVore, MD

Role: backup

Amy Browning

Role: primary

Habeeb Mohammed

Role: primary

Bhruga Shah

Role: primary

Other Identifiers

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23-069-TRP

Identifier Type: -

Identifier Source: org_study_id

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