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Utility of Donor-Derived Cell Free DNA in Association With Gene Expression Profiling (D-OAR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02178943
Recruitment Status : Recruiting
First Posted : July 1, 2014
Last Update Posted : January 30, 2019
Information provided by (Responsible Party):

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.

Condition or disease
Cardiac Transplant Failure Cardiac Transplant Rejection Heart Diseases

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.

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 100 participants
Observational Model: Case-Only
Time Perspective: Prospective
Target Follow-Up Duration: 3 Years
Official Title: Utility of Donor-Derived Cell-free DNA in Association With Gene-Expression Profiling (AlloMap®) in Heart Transplant Recipients (D-OAR)
Study Start Date : June 2014
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : February 2020

Resource links provided by the National Library of Medicine

Heart Transplant Recipients
Heart allograft recipients undergoing scheduled surveillance visits that are part of a long-term management plan.

Primary Outcome Measures :
  1. Clinical Outcomes (Vital Status of Heart Transplant Recipients) [ Time Frame: 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)

Biospecimen Retention:   Samples With DNA
donor derived cf-DNA

Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Heart allograft recipients undergoing scheduled surveillance visits that are part of a long-term management plan.

Inclusion Criteria

  1. Any heart transplant recipient eligible for initiation and participation in the Outcomes AlloMap Registry (OAR) Study of regular AlloMap testing.
  2. Patients can be enrolled any time as long as they have not had more than 1 prior AlloMap.
  3. Written informed consent must be obtained prior to study enrollment. Exclusion Criteria

1. Pregnant Women.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02178943

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Contact: Preethi Prasad 415-287-2558

Show Show 28 study locations
Sponsors and Collaborators
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Study Director: James P Yee CareDx Inc (formerly XDx Inc) Brisbane, CA
Additional Information:
Publications of Results:
Kobashigawa, JA. et al; Initial Analysis of the Donor-Derived Cell-Free DNA -Outcomes AlloMap Registry (D-OAR) Study in Heart Transplant Recipients Undergoing Surveillance for Rejection. 2016 ISHLT 36th Annual Meeting and Scientific Sessions. April 27-30, 2016; Washington, DC

Other Publications:
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Responsible Party: CareDx Identifier: NCT02178943    
Other Study ID Numbers: SN-C-00004
First Posted: July 1, 2014    Key Record Dates
Last Update Posted: January 30, 2019
Last Verified: January 2019
Keywords provided by CareDx:
Molecular Diagnostics
Heart Transplantation
Risk Factors
Additional relevant MeSH terms:
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Heart Diseases
Cardiovascular Diseases