Heart TransplantDEFINE-HTNCT05309382
Development of Non-invasive Cell-free DNA to Supplant Invasive Biopsy in Heart Transplantation
An observational study of Heart Transplant, run by Natera, Inc. at 9 sites in United States.
Trial summary
This is a prospective, multicenter observational, unblinded, longitudinal cohort study. Subjects will be enrolled into the study prior to or at the time of heart transplantation. All subjects will follow the center's standard of care surveillance schedule. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Transplant
- What is being tested?
- Prospera
- How many people
- 147 participants
- Where
- 9 sitesUnited States
- Study dates
- 12 Dec 2022to 2 Oct 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
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
Study population: Heart transplant rejection
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.
- 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.
- Pregnant.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Northwestern Memorial Hospital
Chicago, Illinois, 60611
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Inova Heart and Vascular Institute
Falls Church, Virginia, 22042
Mayo Clinic
Jacksonville, Florida, 32224
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Vanderbilt University Medical Center
Nashville, Tennessee, 37332
University of Utah
Salt Lake City, Utah, 84112
University of California, San Diego
San Diego, California, 92103
About this study
Official title: Development of Non-invasive Cell-free DNA to Supplant Invasive Biopsy in Heart Transplant
This is a prospective, multicenter observational, unblinded, longitudinal cohort study. Subjects will be enrolled into the study prior to or at the time of heart transplantation. All subjects will follow the center's standard of care surveillance schedule. Blood samples will be collected for Prospera testing at the time any surveillance or for-cause testing, which may include endomyocardial biopsy (EMB), echocardiography or other cardiac imaging studies, and/or molecular testing, is performed.
Read the detailed description
Subjects will undergo surveillance monitoring for rejection per the institution's standard clinical care schedule after transplant. Surveillance procedures may include EMB, imaging such as echocardiography, and/or molecular testing. Surveillance is expected to occur at this approximate schedule during the 12 months post-transplant:
- Weekly during month 1
- Every other week months 2-3
- Monthly during months 4-6
- Every 1-3 months during months 7-12
For-cause testing for rejection will be performed as clinically indicated and per the institution's standard clinical care. Prospera testing will be performed at the time each standard of care (SOC) rejection surveillance procedure and at the time of each for-cause testing for rejection. Prospera test results will be provided to the clinical team.
Additional blood samples for research only will be collected at the time of each Prospera blood sample collection. Results of testing performed on research blood samples will not be returned to investigators for use in clinical care.
Study central laboratory or central review for research purposes will include:
- Central pathology review (all EMBs, includes for-cause EMBs).
- Central echocardiography review at day 30 (± 14 days), month 6 (± 30 days) and month 12 (± 30 days) post-transplant.
- Central testing of PRA/DSA pre-transplant (between enrollment and transplant), at day 30 (± 14 days), month 6 (± 30 days) and month 12 (± 30 days) post-transplant.
Central pathology and echocardiography review will be performed using uploaded images obtained from procedures performed as part of routine clinical care. Central pathology review, central echocardiography review and central laboratory PRA/DSA are for research purposes; these data will be reviewed during the analysis phase of the study and results will not be returned to investigators for use in clinical care.
The study period will start at enrollment and conclude with the final visit at 12 months +/- 30 days post-transplant.
This study will generate additional preliminary data to be used in the design and implementation of a subsequent confirmatory clinical utility trial.
The primary objectives are to:
- Describe the association between Prospera dd-cfDNA measures and other diagnostic tests used to detect heart allograft rejection and/or injury, including histology, echocardiography and DSA, in the first post-transplant year
- Inform rates of clinical outcomes in a contemporary cohort of adult heart transplant recipients to determine power for a future randomized, controlled clinical trial.
The secondary objectives are to determine:
- The performance characteristics of the Prospera dd-cfDNA assay to discriminate biopsyproven acute rejection (AR).
- The performance characteristics of the Prospera dd-cfDNA assay to discriminate acute cellular rejection (ACR).
- The performance characteristics of the Prospera dd-cfDNA assay to discriminate antibody mediated rejection (AMR).
- The association between dd-cfDNA levels and donor specific antibodies.
- The association between dd-cfDNA levels and allograft dysfunction as measured by echocardiography.
- The association between dd-cfDNA levels and allograft hemodynamics as measured by right heart catheterization.
- The association between dd-cfDNA levels and future adverse clinical outcomes.
- The effect of treatment for rejection on dd-cfDNA.
- The variability of dd-cfDNA by patient characteristics, including race and gender.
- The variability of dd-cfDNA across donor-recipient characteristics, including gender and race mismatch.
- The association between dd-cfDNA (fraction and absolute level) and predicted heart mass.
- The association between dd-cfDNA levels and time since transplant.
- The association between dd-cfDNA levels and rejection with hemodynamic compromise (requiring inotropes and/or mechanical circulatory support).
- The association between dd-cfDNA levels and incidence of cardiac allograft vasculopathy at one year.
- The association between dd-cfDNA levels and different regimens of immunosuppression
- Conditions
- Heart Transplant
- Being tested
- Prospera
- Keywords
- Prospera, dd-cfDNA, Heart, Transplant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProsperaDiagnostic test
Monthly testing and results provided
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Molecular Endpoint
Percent and quantity of donor-derived cell-free DNA (dd-cfDNA) measured via the Prospera test.
Measured: 1 year
Primary clinical endpoint*
Incidence of the composite endpoint of treated rejection, graft dysfunction, re-transplantation, or death at 12 months after transplant.
*Clinical endpoints are defined as follows:
- Treated rejection: treated biopsy proven rejection (ISHLT ACR Grade ≥ 2R or AMR Grade ≥ pAMR1) or biopsy-negative rejection treated with pulse-dose steroids, monoclonal antibodies, plasmapheresis and/or intravenous immunoglobulin (IVIg).
- Graft dysfunction: left ventricular ejection fraction (LVEF) decline >10% from baseline and < 50% absolute LVEF by echocardiography.
- Re-transplantation: being listed for re-transplant or being re-transplanted.
- Death due to any cause.
Measured: 12 months
Secondary outcomes (1)
Secondary Endpoints
The secondary endpoints are:
- Incidence of the individual components of the primary composite endpoint at 12 months after transplant.
- The incidence at 12 months of:
- Rejection with hemodynamic compromise (requiring inotropes and/or mechanical circulatory support);
- The development of de novo donor specific antibodies;
- Cardiac allograft vasculopathy.
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 posted4 Apr 2022
- Study start12 Dec 2022
- Primary completion2 Oct 2024
- Study completion2 Oct 2024
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 TransplantStudies of the same condition, open and under way.
- More trials run by Natera, Inc.The sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 147 participants (actual)
Sponsor and investigators
- Lead sponsor
- Natera, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael Olymbios, MD, Study director, Natera, Inc.Palak Shah, MD, Principal investigator, Inova Health Care ServicesJosef Stehlik, MD, Study chair, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05309382
- Sponsor's protocol ID
- 22-062-TRP
- Acronym
- DEFINE-HT
- Status last verified
- Oct 2024
- First submitted
- 25 Mar 2022
- Last updated
- 29 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Shah P, Kim PJ, Schlendorf KH, Baran DA, Colvin MM, DeVore AD, Eisen HJ, Ghafourian K, Givertz MM, Hsich E, Kennedy JLW, Kransdorf EP, Nativi-Nicolau JN, Patel J, Tseliou E, Wever-Pinzon O, Doud A, Bloom MS, Carey SA, Kaur N, Biagini DG, Marshall KE, Olympios M, Mehra MR, Stehlik J. Donor-Derived Cell-Free DNA as a Prognostic Biomarker After Heart Transplantation: The DEFINE-HT Study. JACC Heart Fail. 2026 Jul;14(7):103152. doi: 10.1016/j.jchf.2026.103152. Epub 2026 Jun 5.
PubMed 42246920
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Development of Non-invasive Cell-free DNA to Supplant Invasive Biopsy in Heart Transplant
- ClinicalTrials.gov ID
- NCT05309382
- Acronym / sponsor ID
- DEFINE-HT / 22-062-TRP
- Conditions
- Heart Transplant
- Keywords
- Prospera, dd-cfDNA, Heart, Transplant
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 147 participants (actual)
- Lead sponsor
- Natera, Inc.Industry (pharma, biotech, devices)
- Study start
- 12 Dec 2022 (actual)
- Primary completion
- 2 Oct 2024 (actual)
- Study completion
- 2 Oct 2024 (actual)
- First posted
- 4 Apr 2022 (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 a prospective, multicenter observational, unblinded, longitudinal cohort study. Subjects will be enrolled into the study prior to or at the time of heart transplantation. All subjects will follow the center's standard of care surveillance schedule. Blood samples will be collected for Prospera testing at the time any surveillance or for-cause testing, which may include endomyocardial biopsy (EMB), echocardiography or other cardiac imaging studies, and/or molecular testing, is performed.
Detailed description
Subjects will undergo surveillance monitoring for rejection per the institution's standard clinical care schedule after transplant. Surveillance procedures may include EMB, imaging such as echocardiography, and/or molecular testing. Surveillance is expected to occur at this approximate schedule during the 12 months post-transplant:
- Weekly during month 1
- Every other week months 2-3
- Monthly during months 4-6
- Every 1-3 months during months 7-12
For-cause testing for rejection will be performed as clinically indicated and per the institution's standard clinical care. Prospera testing will be performed at the time each standard of care (SOC) rejection surveillance procedure and at the time of each for-cause testing for rejection. Prospera test results will be provided to the clinical team.
Additional blood samples for research only will be collected at the time of each Prospera blood sample collection. Results of testing performed on research blood samples will not be returned to investigators for use in clinical care.
Study central laboratory or central review for research purposes will include:
- Central pathology review (all EMBs, includes for-cause EMBs).
- Central echocardiography review at day 30 (± 14 days), month 6 (± 30 days) and month 12 (± 30 days) post-transplant.
- Central testing of PRA/DSA pre-transplant (between enrollment and transplant), at day 30 (± 14 days), month 6 (± 30 days) and month 12 (± 30 days) post-transplant.
Central pathology and echocardiography review will be performed using uploaded images obtained from procedures performed as part of routine clinical care. Central pathology review, central echocardiography review and central laboratory PRA/DSA are for research purposes; these data will be reviewed during the analysis phase of the study and results will not be returned to investigators for use in clinical care.
The study period will start at enrollment and conclude with the final visit at 12 months +/- 30 days post-transplant.
This study will generate additional preliminary data to be used in the design and implementation of a subsequent confirmatory clinical utility trial.
The primary objectives are to:
- Describe the association between Prospera dd-cfDNA measures and other diagnostic tests used to detect heart allograft rejection and/or injury, including histology, echocardiography and DSA, in the first post-transplant year
- Inform rates of clinical outcomes in a contemporary cohort of adult heart transplant recipients to determine power for a future randomized, controlled clinical trial.
The secondary objectives are to determine:
- The performance characteristics of the Prospera dd-cfDNA assay to discriminate biopsyproven acute rejection (AR).
- The performance characteristics of the Prospera dd-cfDNA assay to discriminate acute cellular rejection (ACR).
- The performance characteristics of the Prospera dd-cfDNA assay to discriminate antibody mediated rejection (AMR).
- The association between dd-cfDNA levels and donor specific antibodies.
- The association between dd-cfDNA levels and allograft dysfunction as measured by echocardiography.
- The association between dd-cfDNA levels and allograft hemodynamics as measured by right heart catheterization.
- The association between dd-cfDNA levels and future adverse clinical outcomes.
- The effect of treatment for rejection on dd-cfDNA.
- The variability of dd-cfDNA by patient characteristics, including race and gender.
- The variability of dd-cfDNA across donor-recipient characteristics, including gender and race mismatch.
- The association between dd-cfDNA (fraction and absolute level) and predicted heart mass.
- The association between dd-cfDNA levels and time since transplant.
- The association between dd-cfDNA levels and rejection with hemodynamic compromise (requiring inotropes and/or mechanical circulatory support).
- The association between dd-cfDNA levels and incidence of cardiac allograft vasculopathy at one year.
- The association between dd-cfDNA levels and different regimens of immunosuppression
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Heart transplant rejection
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.
- Able and willing to comply with the study visit schedule, study procedures, and study requirements.
Key exclusion criteria (3 listed)
- Concurrent multiple solid organ or tissue transplants.
- Prior history of any organ or cellular transplantation.
- Pregnant.
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 |
|---|---|---|
| ProsperaMonthly testing and results provided | Diagnostic test | – |
Primary outcome
Primary Molecular Endpoint
Time frame: 1 year
Percent and quantity of donor-derived cell-free DNA (dd-cfDNA) measured via the Prospera test.
Primary clinical endpoint*
Time frame: 12 months
Incidence of the composite endpoint of treated rejection, graft dysfunction, re-transplantation, or death at 12 months after transplant. *Clinical endpoints are defined as follows: 1. Treated rejection: treated biopsy proven rejection (ISHLT ACR Grade ≥ 2R or AMR Grade ≥ pAMR1) or biopsy-negative rejection treated with pulse-dose steroids, monoclonal antibodies, plasmapheresis and/or intravenous immunoglobulin (IVIg). 2. Graft dysfunction: left ventricular ejection fraction (LVEF) decline >10% from baseline and < 50% absolute LVEF by echocardiography. 3. Re-transplantation: being listed for re-transplant or being re-transplanted. 4. Death due to any cause.
1 secondary outcome
Secondary Endpoints
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2024.
- Derived from this study: PubMed 42246920Shah P, Kim PJ, Schlendorf KH, Baran DA, Colvin MM, DeVore AD, Eisen HJ, Ghafourian K, Givertz MM, Hsich E, Kennedy JLW, Kransdorf EP, Nativi-Nicolau JN, Patel J, Tseliou E, Wever-Pinzon O, Doud A, Bloom MS, Carey SA, Kaur N, Biagini DG, Marshall KE, Olympios M, Mehra MR, Stehlik J. Donor-Derived Cell-Free DNA as a Prognostic Biomarker After Heart Transplantation: The DEFINE-HT Study. JACC Heart Fail. 2026 Jul;14(7):103152. doi: 10.1016/j.jchf.2026.103152. Epub 2026 Jun 5.
- Individual participant dataSharing planned: No
Related trials for Heart Transplant
Not yet recruiting
Autologous Thymus Transplant in Children With Congenital Heart Disease: A Pilot Study
Congenital Heart Disease (CHD)
Not yet recruitingPhase 4
Roxadustat and Myocardial Injury After Off-Pump Coronary Artery Bypass Surgery
Coronary Artery Disease, Coronary Artery Bypass Grafting
RecruitingObservational study
Preoperative Gastric Ultrasound and Left Ventricular Function in Coronary Artery Bypass Surgery
Coronary Artery Disease, Left Ventricular Systolic Dysfunction
RecruitingEarly Phase 1
Thiamine Intervention and Coronary Artery Bypass Grafting
Coronary Heart Disease, Coronary Artery Bypass Grafting
Not yet recruitingObservational study
Preoperative Gastric Ultrasound and Anaesthetic Management in Patients Undergoing Coronary Artery Bypass Grafting
Preoperative Fasting, Pulmonary Aspiration During Anesthetic Induction
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.
Palak Shah, MD principal investigator
Inova Health Care Services
Josef Stehlik, MD study chair
University of Utah
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Transplant, run by Natera, Inc. at 9 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 3 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: finished, as of the sponsor's last update on 29 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 Molecular Endpoint (time frame: 1 year). The study lists 2 primary outcomes in all. 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 NCT05309382, 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 29 Oct 2024.