Diagnostic Tests for Heart Transplant Rejection

Recruiting at 17 trial locations

Overseen By Robert Polakowski, PhD

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: University of Alberta

Disqualifiers: Decline participation, Multiple organs, others

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

Compensation: Varies

Number of Visits: Unknown

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the relationship between certain blood markers and heart transplant success. Specifically, it examines levels of DD-cfDNA (a type of genetic material shed by cells) and HLA antibodies, comparing them to results from a special diagnostic test called MMDx. The goal is to better understand how these factors can indicate the health of a transplanted heart. Participants should be heart transplant recipients already scheduled for a biopsy, either as part of their normal care or due to high risk. As a Phase 2 trial, this research measures how well these markers work in an initial, smaller group, offering participants a chance to contribute to important advancements in transplant care.

Do I need to stop my current medications for the trial?

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 MMDx diagnostic test is safe for heart transplant recipients?

Research has shown that HLA antibody treatments have been used safely and effectively in heart transplants, indicating they are generally well-tolerated. However, these antibodies can sometimes increase the risk of complications, such as organ rejection.

The MMDx test checks for early signs of heart transplant issues and has demonstrated an improved ability to detect problems early. Although studies on its safety are limited, it is primarily a diagnostic tool and is generally considered low-risk.

The Prospera test is a blood test that assesses the health of a transplanted heart. It has been clinically validated, meaning it has been tested and proven effective. As a noninvasive procedure, it does not require surgery, making it a safe option for patients.

Overall, the treatments and tests in the trial have demonstrated good safety records. They help manage and monitor heart transplants without causing significant harm. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Trifecta-Heart cfDNA-MMDx study because it explores innovative ways to improve heart transplant care. Unlike traditional methods that rely heavily on invasive biopsies to monitor heart transplant health, this study examines the use of cell-free DNA (cfDNA) and MMDx diagnostic tests, which could provide less invasive and more accurate assessments. The Prospera test, which measures donor-derived cfDNA, offers a non-invasive way to detect rejection early. These advancements have the potential to enhance patient monitoring and outcomes by providing timely and precise information, reducing the need for frequent invasive procedures.

What evidence suggests that this trial's treatments could be effective for heart transplant patients?

Research has shown that certain antibodies, known as anti-HLA antibodies, can develop before or after a heart transplant and may affect long-term survival. Specifically, patients with these antibodies often have a lower survival rate 15 years post-transplant. This trial examines the MMDx diagnostic test to gain better insights into heart transplant health, though further research is needed to confirm its reliability compared to traditional methods. The Prospera test, also under study in this trial, shows promise in predicting heart transplant outcomes, as it effectively detects rejection with fewer false positives than some other tests. These tools and tests aim to improve care and outcomes for heart transplant patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Philip F Halloran, MD PhD

Principal Investigator

Alberta Transplant Applied Genomics Center, University of Alberta

Are You a Good Fit for This Trial?

Inclusion Criteria

All heart transplant recipients undergoing a biopsy for clinical indications and protocol biopsies, as determined by their physician or surgeon, will be eligible to enroll in the study.

Patients are enrolled based on standard of care biopsies, including surveillance biopsies in high-risk patients, with informed consent.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Biopsy and Blood Sample Collection

Collection of biopsies and blood samples for calibration of DD-cfDNA levels against MMDx measurements

6 months

Multiple visits for biopsy and blood sample collection

Calibration and Analysis

Calibration of DD-cfDNA test cut-off values against MMDx biopsy diagnoses for TCMR, ABMR, and heart injury

18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• HLA antibody
• MMDx diagnostic test
• Prospera

How Is the Trial Designed?

Group I: Heart transplant protocol and for cause biopsies Experimental Treatment 3 Interventions

The study population includes patients with a functioning heart transplant undergoing a biopsy for clinical indications as standard of care, or protocol biopsies of heart in high-risk patients, or follow-up after treatment.

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Natera, Inc.

Industry Sponsor

Trials

56

Recruited

50,700+

One Lambda

Collaborator

Trials

3

Recruited

1,200+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6531009/

Impact of pretransplant antibodies on outcomes after heart ... Patients with de novo antibodies that appear more than one year after transplantation had the worst prognosis, with a 15-year survival rate of 47%. Recent data ...

2. jhltonline.org jhltonline.org/article/S1053-2498(25)01775-9/fulltext

Summary of the International Society for Heart and ... In the pretransplant period, the more antibodies detected in a patient awaiting heart transplantation often significantly reduces the chance of ...

3. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00004/full

Significance of Anti-HLA Antibodies on Adult and Pediatric ... Using the Pediatric Heart Transplant Study database, the reported incidence of AMR was 11% (among 1,596 recipients), and patient and GS were lower for those ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0966327422001800

Significance of HLA-matching and anti-HLA antibodies in ... Our study showed that in our cohort of heart transplant patients, HLA matching did not influence overall survival, whether studied by the number of MM or by the ...

5. nejm.org nejm.org/doi/full/10.1056/NEJM199403243301203

The Influence of HLA Compatibility on Graft Survival after ... Thus, transplants with two HLA-A, B, or DR mismatches had an approximately 25 percent greater likelihood of failing within three years of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5269448/

Significance of Anti-HLA Antibodies on Adult and Pediatric ... Antibodies against HLA can be found in patients prior to transplantation after exposure to foreign HLA through blood transfusion, pregnancy, previous transplant ...

7. jacc.org jacc.org/doi/10.1016/j.jchf.2023.01.019

How to Approach HLA Sensitization in Heart Transplant ... This method has proven safe and successful in HT. The MFI threshold will vary between different immunogenetics laboratories, but generally it is over 5,000. By ...

8. jhltonline.org jhltonline.org/article/S1053-2498(18)31292-0/fulltext

The management of antibodies in heart transplantation Pre-transplant antibodies can reduce the likelihood of obtaining a compatible donor heart and may increase the risk of rejection after heart ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S1600613522096885

Incidence, characterization, and impact of newly detected ... The detection of “de novo” donor-specific anti-HLA antibodies (DSAs) has been associated with worse outcomes in adult heart, kidney, and lung transplantation.1, ...

10. ahajournals.org ahajournals.org/doi/10.1161/JAHA.118.011124

Human Leukocyte Antigen‐Based Risk Stratification in ... The purpose of this study is to reexamine whether HLA mismatch may be used in risk stratification to improve outcomes in heart transplantation.