Prospera Test for Heart Transplant Rejection

(ACES-EMB Trial)

Recruiting at 10 trial locations

Overseen By Kiara Stoddard

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Natera, Inc.

Disqualifiers: Multiple transplants, Prior transplants, Pregnant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of the Prospera™ Test in monitoring heart transplant rejection. Participants will be randomly assigned to either Prospera surveillance or traditional biopsy (EMB) surveillance to determine which method better detects rejection. The trial focuses on individuals being evaluated for or on the waiting list for a heart transplant. It is ideal for those who will soon receive a heart transplant and can adhere to the study's schedule and procedures. As an unphased trial, this study offers participants the chance to contribute to innovative research that could enhance heart transplant care.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that the Prospera Test is safe for heart transplant rejection surveillance?

Research shows that the Prospera™ Test, which uses cell-free DNA, effectively identifies heart transplant rejection. Studies have found it to be highly accurate, correctly detecting rejection and minimizing false alarms. It outperforms some older tests, reducing false positives by over 37%.

For safety, this test is non-invasive, requiring only a blood sample. This makes it easier on patients compared to more invasive methods. No major side effects have been reported in these studies, making it a promising option for monitoring heart transplant patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Prospera™ Test for heart transplant rejection because it offers a new way of monitoring patients using donor-derived cell-free DNA (dd-cfDNA) levels. Unlike traditional endomyocardial biopsies, which are invasive and can be uncomfortable, the Prospera Test is non-invasive and provides results that help assess the risk of acute rejection. This test can potentially reduce the need for frequent biopsies, making the monitoring process easier and more patient-friendly while still providing critical information about the health of the transplanted heart.

What evidence suggests that the Prospera Test is effective for heart transplant rejection surveillance?

This trial will compare the Prospera™ Test with standard endomyocardial biopsy (EMB) surveillance for detecting heart transplant rejection. Studies have shown that the Prospera™ Test effectively detects heart transplant rejection. It has strong sensitivity and specificity, accurately identifying those at risk and those not. The test reduces false alarms by over 37%, making it more reliable than some other methods. It measures a specific type of DNA from the donor, which can signal rejection early. Early detection might help initiate treatment sooner, potentially improving outcomes for heart transplant patients. ^{2 4 6 7 8}

Who Is on the Research Team?

Michael Olymbios, MD

Principal Investigator

Natera, Inc.

Josef Stehlik, MD

Principal Investigator

University of Utah

Palak Shah, MD

Principal Investigator

Inova Schar Heart and Vascular

Are You a Good Fit for This Trial?

This trial is for adults over 18 who can consent, are being evaluated for or on the waiting list for a heart transplant, and willing to follow the study's visit schedule and procedures. It excludes those unable to meet these requirements.

Inclusion Criteria

Able and willing to comply with the study visit schedule, study procedures and study requirements

I am being evaluated for or am on the waiting list for 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

Exclusion Criteria

Planned use of other commercially available or investigational cfDNA or gene expression profile assays for rejection surveillance

Pregnant

I have had multiple organ or tissue transplants.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Post-Transplant Surveillance

All subjects follow the center's standard of care surveillance schedule from transplant through 4 weeks post-transplantation, with EMB occurring roughly weekly or bi-weekly.

4 weeks

Weekly or bi-weekly visits

Randomized Surveillance

Subjects are randomized 30 days post-transplant to either Prospera surveillance or EMB surveillance, following the institutional standard of care schedule.

11 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including quality of life assessments at week 4, month 6, and month 12 post-transplant.

12 months

What Are the Treatments Tested in This Trial?

Interventions

• The Prospera™ Test

Trial Overview The study compares two methods of monitoring heart transplant rejection: Prospera™ Test (blood test) versus Endomyocardial Biopsy (tissue sample). Patients will be assigned randomly in a 2:1 ratio favoring Prospera after their transplant.

How Is the Trial Designed?

Group I: Prospera Surveillance Cohort Experimental Treatment 1 Intervention

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 II: Endomyocardial Biopsy Surveillance Cohort Active Control 1 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 Is Running the Clinical Trial?

Natera, Inc.

Lead Sponsor

Trials

56

Recruited

50,700+

Published Research Related to This Trial

In a study involving 26 heart transplant patients, the use of a local laboratory-run dd-cfDNA assay allowed for effective monitoring of graft health, enabling 88% of invasive endomyocardial biopsies to be avoided without missing any cases of rejection.

The results demonstrate that dd-cfDNA is a feasible and reliable non-invasive method for rejection surveillance in heart transplant patients, significantly reducing the need for more invasive procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local laboratory-run donor-derived cell-free DNA assay for rejection surveillance in heart transplantation-first six months of clinical experience. Teszak, T., Bödör, C., Hegyi, L., et al.[2023]

In a study of 82 kidney transplant recipients, the use of donor-derived cell-free DNA (dd-cfDNA) testing identified acute rejection in 3 out of 5 patients who underwent biopsy, suggesting it can help detect rejection events.

However, the overall benefit of routine dd-cfDNA monitoring was marginal, as most patients with negative tests did not show significant issues, indicating that the cost-effectiveness of this testing in low-risk patients may need further evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol-based donor-derived cell-free DNA surveillance in kidney transplant recipients: A single-center experience. Nissaisorakarn, P., Patel, H., Amtul, A., et al.[2022]

Donor-derived cell-free DNA (dd-cfDNA) is a promising biomarker for early diagnosis of kidney transplant rejection, with assays like Allosure and Prospera receiving Medicare approval for their diagnostic value.

The review highlights the importance of considering factors such as the type of rejection (antibody-mediated or T-cell mediated), timing of the test, and background levels of cell-free DNA to optimize the use of dd-cfDNA assays in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical value of donor-derived cell-free DNA measurements in kidney transplantation. Garg, N., Mandelbrot, DA., Parajuli, S., et al.[2021]

In a study involving 428 samples from 112 heart transplant patients, donor-derived cell-free DNA (dd-cfDNA) testing demonstrated high specificity (82% for standard and 84% for expanded SNP assays) for detecting acute rejection (AR), but low sensitivity (39%).

The study found that dd-cfDNA testing was more specific than gene-expression profiling (GEP) for AR detection, suggesting that dd-cfDNA could be a better alternative to GEP in clinical practice, although both methods showed low sensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of two donor-derived cell-free DNA tests and a blood gene-expression profile test in heart transplantation. Rodgers, N., Gerding, B., Cusi, V., et al.[2023]

In a study of 170 lung transplant recipients, donor-derived cell-free DNA (dd-cfDNA) levels were found to be significantly higher in patients experiencing acute rejection (AR) compared to those with stable conditions, indicating its potential as a biomarker for monitoring transplant rejection.

The study established specific thresholds for dd-cfDNA: 1.17% for diagnosing AR with high sensitivity (89.19%) and specificity (86.47%), and 0.89% for chronic lung allograft dysfunction (CLAD) with even higher sensitivity (95.00%), suggesting dd-cfDNA is a promising noninvasive tool for assessing lung allograft injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of plasma donor-derived cell free DNA for lung allograft rejection diagnosis in lung transplant recipients. Ju, C., Xu, X., Zhang, J., et al.[2023]

In a study of 87 heart transplant recipients, circulating graft-derived cell-free DNA (dd-cfDNA) levels were found to be significantly higher in patients experiencing biopsy-proven cardiac rejection compared to clinically stable patients, indicating its potential as a noninvasive marker for rejection diagnostics.

The study also revealed that dd-cfDNA levels could increase up to 30 days before a biopsy confirmed rejection, suggesting it may serve as an early warning signal; however, factors like pericardial effusions and timing of sample collection post-biopsy can affect the accuracy of dd-cfDNA measurements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Graft-derived Cell-free DNA as a Noninvasive Biomarker of Cardiac Allograft Rejection: A Cohort Study on Clinical Validity and Confounding Factors. Knüttgen, F., Beck, J., Dittrich, M., et al.[2023]

Citations

1. natera.com natera.com/company/news/prospera-heart-test-with-dqs-outperforms-dd-cfdna-percentage-in-detecting-allograft-rejection-new-ajt-publication-shows/

Prospera™ Heart Test with DQS Outperforms dd-cfDNA ... Study published in American Journal of Transplantation highlights strong sensitivity and specificity, along with a >37% reduction in false positives when using ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05205551

Prospera Test Evaluation in Cardiac Transplant (ProTECT) The secondary endpoints are: The predictive performance of the Prospera™ test in detecting rejection or allograft dysfunction after heart transplant as measured ...

3. amjtransplant.org amjtransplant.org/article/S1600-6135(25)00226-6/fulltext

A two-threshold algorithm using donor-derived cell-free ... Data are presented as mean (95% confidence interval). Based on a cohort rejection prevalance of 8.74%.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11335081/

Elevation of Donor-derived Cell-free DNA Before Biopsy ... Donor-derived cell-free DNA (dd-cfDNA) shows promise as an early indicator of rejection, allowing earlier and possibly more effective treatment.

5. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT06414603

Effectiveness Study in Heart Transplant Patients of Rejection ... Prospera cfDNA level < 0.15% will be interpreted as low risk for acute rejection (AR). Prospera cfDNA ≥ 0.15% will be interpreted as increased ...

6. natera.com natera.com/organ-health/prospera-heart-transplantation-assessment/

Prospera Heart Overview | Cell-Free DNA Testing Only Prospera™ Heart with DQS provides two donor derived cell-free DNA metrics and has been shown to improve accuracy in screening for acute cellular rejection ...

7. investor.natera.com investor.natera.com/news/news-details/2025/Prospera-Heart-Test-with-DQS-Outperforms-dd-cfDNA-Percentage-in-Detecting-Allograft-Rejection-New-AJT-Publication-Shows/default.aspx

Prospera™ Heart Test with DQS Outperforms dd-cfDNA ... Study published in American Journal of Transplantation highlights strong sensitivity and specificity, along with a >37% reduction in false positives when using ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9670834/

A novel donor-derived cell-free DNA assay for the ... This study describes the performance of the Prospera dd-cfDNA test in detecting AR in adult heart transplant recipients. Analysis of 811 ...