Heart Transplant Failure and RejectionACES-EMBNCT06414603
A Comparative Effectiveness Study in Heart Transplant Patients of Rejection Surveillance With Cell-free DNA Versus Endomyocardial Biopsy
A study testing The Prospera™ Test in people with Heart Transplant Failure and Rejection, run by Natera, Inc. at 16 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Transplant Failure and Rejection
- What is being tested?
- The Prospera™ Test
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 16 sitesUnited States
- Study dates
- 10 Jun 2024to Feb 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United States16 sites
University of Michigan
Ann Arbor, Michigan, 48109
University of Colorado
Aurora, Colorado, 80045
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Medical University of South Carolina
Charleston, South Carolina, 29425
University of Texas, Southwestern Medical Center
Dallas, Texas, 75390
Duke University
Durham, North Carolina, 27710
Inova Schar Heart and Vascular Institute
Falls Church, Virginia, 22042
Mayo Clinic
Jacksonville, Florida, 32224
Kansas University Medical Center
Kansas City, Kansas, 66160
Cedars-Sinai Medical Center
Los Angeles, California, 90048
NYU Langone Health
New York, New York, 10016
AdventHealth Orlando
Orlando, Florida, 32804
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
University of Utah
Salt Lake City, Utah, 84112
University of California, San Diego
San Diego, California, 92103
Baylor Scott White - Temple
Temple, Texas, 76508
About this study
Official title: A Comparative Effectiveness Study in Heart Transplant Patients of Rejection Surveillance With Cell-free DNA Versus Endomyocardial Biopsy (ACES-EMB)
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.
Read the detailed description
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
- Heart Transplant Failure and Rejection
- Being tested
- The Prospera™ Test
- Keywords
- Heart Transplant
- Medical subject headings
- Rejection, Psychology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
The Prospera™ TestDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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:
- Rejection: ISHLT ACR Grade ≥ 2R or AMR Grade ≥ pAMR1
- Graft dysfunction: LVEF decline ≥ 10% from baseline and < 50% absolute LVEF by echocardiography
- 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).
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2024
- Study start10 Jun 2024
- Primary completionFeb 2027 (estimated)
- Study completionFeb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart Transplant Failure and RejectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Natera, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael Olymbios, MD, Study director, Natera, Inc.Josef Stehlik, MD, Study chair, University of UtahPalak Shah, MD, Study chair, Inova Schar Heart and Vascular
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06414603
- Sponsor's protocol ID
- 23-069-TRP
- Acronym
- ACES-EMB
- Status last verified
- Feb 2026
- First submitted
- 2 May 2024
- Last updated
- 27 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 41492943
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Comparative Effectiveness Study in Heart Transplant Patients of Rejection Surveillance With Cell-free DNA Versus Endomyocardial Biopsy (ACES-EMB)
- ClinicalTrials.gov ID
- NCT06414603
- Acronym / sponsor ID
- ACES-EMB / 23-069-TRP
- Conditions
- Heart Transplant Failure and Rejection
- Keywords
- Heart Transplant
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Natera, Inc.Industry (pharma, biotech, devices)
- Study start
- 10 Jun 2024 (actual)
- Primary completion
- Feb 2027 (estimated)
- Study completion
- Feb 2027 (estimated)
- First posted
- 16 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prospera Surveillance Cohort | Experimental | Diagnostic Test: The Prospera™ TestSubjects 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. |
| 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| The Prospera™ TestThe 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. | Diagnostic test | Prospera Surveillance Cohort |
Primary outcome
Primary Clinical Endpoint
Time frame: 12 months
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).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2026.
- Derived from this study: PubMed 41492943Kim 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Olymbios, MD study director
Natera, Inc.
Josef Stehlik, MD study chair
University of Utah
Palak Shah, MD study chair
Inova Schar Heart and Vascular
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing The Prospera™ Test in people with Heart Transplant Failure and Rejection, run by Natera, Inc. at 16 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 27 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Clinical Endpoint (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06414603, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2026.