Clinical trial NCT06414603: A Comparative Effectiveness Study in Heart Transplant Patients of Rejection Surveillance With Cell-free DNA Versus Endomyocardial Biopsy
Official title: A Comparative Effectiveness Study in Heart Transplant Patients of Rejection Surveillance With Cell-free DNA Versus Endomyocardial Biopsy (ACES-EMB)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Transplant Failure and Rejection
Keywords: Heart Transplant
Lead sponsor: Natera, Inc.
Sponsor class: INDUSTRY
First posted: 2024-05-16
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Primary Clinical Endpoint
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Atlanta
country: United States
facility: Piedmont Healthcare
state: Georgia
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Dallas
country: United States
facility: University of Texas, Southwestern Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Falls Church
country: United States
facility: Inova Schar Heart and Vascular Institute
state: Virginia
Study officials:
affiliation: Natera, Inc.
name: Michael Olymbios, MD
role: STUDY_DIRECTOR
affiliation: University of Utah
name: Josef Stehlik, MD
role: STUDY_CHAIR
affiliation: Inova Schar Heart and Vascular
name: Palak Shah, MD
role: STUDY_CHAIR
References: