Utility of Donor-Derived Cell Free DNA in Association With Gene Expression Profiling
- Conditions
- Cardiac Transplant RejectionCardiac Transplant FailureHeart Diseases
- Registration Number
- NCT02178943
- Lead Sponsor
- CareDx
- Brief Summary
Plasma donor-derived cell-free DNA (dd-cfDNA) is measured as a % of the total plasma cfDNA in association with the measurement of AlloMap, a non-invasive gene expression test to aid in heart transplant management.
- Detailed Description
AlloMap Molecular Expression Testing is performed in a single laboratory, assessing the gene expression profile of RNA isolated from peripheral blood mononuclear cells (PBMC). Per FDA labeling, AlloMap Testing is "intended to aid in the identification of heart transplant recipients with stable allograft function who have a low probability of moderate/severe acute cellular rejection (ACR) at the time of testing in conjunction with standard clinical assessment." AlloMap is the only non-invasive, blood test method recommended in the International Society for Heart and Lung Transplantation (ISHLT) guidelines for surveillance of heart transplant recipients for rejection. More than 52,000 commercial AlloMap tests from more than 12,000 patients have been reported by the XDx Reference Laboratory in Brisbane, California, which is certified under the Clinical Laboratory Improvement Amendment (CLIA) of 1988 and accredited by the College of American Pathologists.
In 2013, a registry study named OAR was initiated to follow long-term outcomes in allograft recipients receiving commercial AlloMap testing for surveillance (NCT01833195). The current objective is to enroll volunteers who are participating in the OAR registry(1) to co-participate in this observational sub-study, named D-OAR, in order to study a new biomarker, dd-cfDNA.
dd-cfDNA has been proposed as a marker for cellular injury caused by rejection(2, 3). Because dd-cfDNA and the AlloMap test measure different signals in the blood, a combination of the two approaches could be additive since AlloMap is a measure of host immune response and dd-cfDNA monitors graft injury.
The dd-cfDNA measurement is intended for the quantitative detection of plasma dd-cfDNA as a % of the total plasma cell-free DNA. Its utility as a surveillance tool in the management of heart transplant recipients is being investigated.
This is an observational sub-study for subjects who are co-enrolled to participate in the Outcomes AlloMap Registry (OAR). Prior to implementation of the amendment dated September 15, 2016, blood specimens were collected for assay of dd-cfDNA levels at each visit that occurred for AlloMap testing, per the OAR Study. As stated in the OAR study, the regular surveillance schedule for testing with AlloMap is determined by each participating center's standard of care. After this protocol amendment, the existing patients will no longer have routine dd-cfDNA specimens drawn to be paired with their standard of care AlloMap. The dd-cfDNA specimen will be drawn only when the patient is scheduled for a for-cause biopsy. New patients may be enrolled any time post-transplant as long as they have not had more than 1 prior AlloMap. These patients will also only undergo routine AlloMap testing as per participating center's standard of care and dd-cfDNA specimen will be drawn when the patient is scheduled for a for-cause biopsy. An AlloMap sample will be drawn for research use along with the dd-cfDNA specimen at the time of the for-cause biopsy where the center's infrastructure permits. An additional two follow-up dd-cfDNA specimens will be collected in the patients that undergo a for-cause biopsy, and are being treated for rejection and/or graft dysfunction, as per their standard of care schedule. The two follow-up visits will not be paired with a research use AlloMap and will be performed within 8 weeks after the for cause event. If a patient returns for another for-cause biopsy, the center may opt to collect another research AlloMap and dd-cfDNA specimen, and two follow-up dd-cfDNA specimens.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 100
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Clinical Outcomes (Vital Status of Heart Transplant Recipients) 3 years Graft dysfunction, Rejection with hemodynamic compromise:
Hemodynamic compromise is defined by the presence of one or more of the following criteria:
Proportional decrease in LVEF ≥ 25%, Absolute LVEF ≤ 30%, Need for inotropic support, Cardiac index \< 2.0 L/min/m2, Death (re-transplantation)
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (28)
Cedars-Sinai Medical Center
🇺🇸Beverly Hills, California, United States
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
Stanford University
🇺🇸Stanford, California, United States
Memorial Regional Hospital
🇺🇸Hollywood, Florida, United States
Tampa General Hospital
🇺🇸Tampa, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
St. Vincent Medical Group
🇺🇸Indianapolis, Indiana, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Mid America Heart Institute - St. Luke's Hospital
🇺🇸Kansas City, Missouri, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Mount Sinai Hospital
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Integris Baptist Medical Center
🇺🇸Oklahoma City, Oklahoma, United States
Drexel University
🇺🇸Philadelphia, Pennsylvania, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Baylor Research Institute
🇺🇸Dallas, Texas, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Baylor St. Lukes
🇺🇸Houston, Texas, United States
Intermountain Heart Institute
🇺🇸Murray, Utah, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Aurora St. Luke's Medical Center
🇺🇸Milwaukee, Wisconsin, United States