Heart Transplant Failure and Rejection
Conditions
Brief summary
The study objective is to demonstrate that rejection surveillance of heart transplant recipients with Prospera dd-cfDNA is non-inferior to rejection surveillance with endomyocardial biopsy and histology in the first post-transplant year.
Detailed description
Subjects will be enrolled into the study while 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. Subjects will be randomized in a 1:1 ratio 30 days (± 7 days) post-transplant to Prospera surveillance (Study Group) versus EMB surveillance (Control Group, standard clinical care). Rejection surveillance (Prospera testing in the Study Group and EMB in the Control Group) will be performed at times corresponding to the institutional standard of care schedule for rejection surveillance. Study Group: Prospera Surveillance (300 Subjects) Subjects will 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 negative and a surveillance EMB will be omitted. Prospera cfDNA ≥ 0.15% will be followed by EMB. A for-cause EMB can be done per the clinical team's discretion at any time. Control Group: EMB Surveillance (standard of care) (300 Subjects) Subjects will undergo surveillance EMB per the institution's standard clinical care. The study intervention will be during the first 12 months post-transplant.
Interventions
DIAGNOSTIC_TESTProspera Transplant Assessment
Prospera™ detects allograft rejection noninvasively and with high accuracy by measuring the fraction of dd-cfDNA in the patient's blood, without the need for prior donor or recipient genotyping. Prospera is a commercially available LDT developed by Natera, Inc. Natera is a laboratory certified under the Clinical Laboratory Improvement Amendments (CLIA).
PROCEDUREEndomyocardial biopsy
Subjects will undergo surveillance EMB per the institution's standard clinical care, which is expected to be approximately every other week in months 2 and 3, then monthly through month 6, then every 1-3 months through the end of month 12.
Sponsors
Natera, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female, age 18 years or older at the time of signing informed consent. 2. On the heart transplant waiting list and expected to receive a heart transplant. 3. Able to read, understand and provide written informed consent. 4. Able and willing to comply with the study visit schedule, study procedures and study requirements.
Exclusion criteria
1. Heart transplantation has been performed. 2. Concurrent multiple solid organ or tissue transplant 3. Prior history of any organ or cellular transplantation. 4. Planned use of other commercially available or investigational cfDNA or gene expression profile assays. 5. Pregnant. 6. Hemodynamically unstable or other serious medical condition that may adversely affect the subject's ability to participate in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Demonstrate the use of Prospera for post-transplant surveillance is non-inferior to the current standard of care, EMB surveillance, with respect to the primary composite endpoint. | 12 months | The primary endpoint of the study is a composite endpoint defined as the first occurrence of one or more of the following events after transplant: 1. Treated rejection with or without graft dysfunction and/or graft dysfunction requiring treatment with pulse dose steroids, monoclonal antibodies, plasmapheresis, and/or intravenous immunoglobulin (IVIg) 2. Graft dysfunction 3. Re-transplantation 4. 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 * Re-transplantation: being listed for re-transplant or being re-transplanted |
Outcome results
None listed