Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT02109575 |
Other study ID # |
CHW 10/83 |
Secondary ID |
R01HL119747 |
Status |
Completed |
Phase |
|
First received |
|
Last updated |
|
Start date |
March 1, 2014 |
Est. completion date |
March 30, 2020 |
Study information
Verified date |
March 2021 |
Source |
Medical College of Wisconsin |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial Summary
The primary goal of this Multicenter Study is to develop and to evaluate a method for
measuring donor-specific cell free DNA in blood samples from transplant recipients as markers
of rejection. Blood samples obtained periodically from heart transplant recipients are
assessed for cell free DNA relative to clinical data in order to determine whether changes in
the level of cell free DNA indicate rejection.
This research study proposes testing a blood sample obtained from the heart transplant
recipient. The research seeks to establish whether this blood test will show when the patient
is beginning to or already rejecting the transplanted heart.
BACKGROUND Identifying if a transplant patient is beginning to or already rejecting the heart
is necessary, so that appropriate treatment can be started to halt the rejection. Heart
catheterization with biopsy is the usual method used for assessing whether a patient may be
rejecting the heart. There are also a number of other methods that transplant physicians will
use to look for signs of rejection including other blood tests, echocardiograms, obtaining
pressure readings during heart catheterization, and micro-array testing of blood obtained
during biopsy. These technologies are limited in ability to consistently and accurately
identify the presence of rejection.
The usual method of checking for rejection involves obtaining a sample of the heart tissue
(heart biopsy); biopsy can only be accomplished through heart catheterization which is an
invasive procedure that has risks associated with disturbing the heart such as puncturing the
heart or causing the heart rate to change or damaging tissue in the heart. Overtime,
repeating this invasive procedure can diminish the ease of the procedure because the veins
can become scarred and more difficult to access. For these reasons, researchers believe that
it would be good to have a blood test that gives information about the possibility of
rejection so that it may not be necessary to do as many heart biopsies. Also, a blood test
may be able to provide information about the heart or about rejection that is currently not
available at all.
Description:
Early detection of rejection is a major focus of organ transplant care. The use of aggressive
immunosuppressive therapy has been shown to alter the prognosis of heart transplant patients
who have acute rejection1. There are many modalities utilized in the routine surveillance of
heart transplant patients, each with limitations. Screening transthoracic echocardiography
focusing on indices of systolic and diastolic dysfunction, along with regional wall
abnormalities, has been shown to have poor sensitivity and does not effectively discriminate
between patients with and without rejection. Newer echocardiographic parameters including
myocardial performance or diastolic velocity indices may be a better means of detecting
subtle changes in cardiac function in the setting of heart transplant, but these tools are
most helpful after the insult caused by rejection has already occurred. Hemodynamic changes
measured during heart catheterization have also been evaluated as a means of detecting
rejection. Rosenthal et al found that although there were statistically significant
differences between patients with higher or lower grades of rejection scores, heart
catheterization did not permit effective discrimination of patients with moderate to severe
rejection. Heart biomarkers, including c-reactive protein, brain natriuretic peptides, and
troponin, have been studied as non-invasive measures of determining heart dysfunction or
rejection. These surrogates are weakly associated with different rejection grades on biopsy
and have a poor predictive capacity for biopsy-detected rejection3. Recently, microarray
technology has been used to screen for genes expressed in heart allograft rejection using
peripheral leukocytes from blood samples obtained at the time of endomyocardial biopsy. This
technique was shown to have a high negative predictive value for the diagnosis of acute
cellular rejection but it is unable to detect low grades of rejection4. Overall, these
technologies are limited in the ability to consistently and accurately predict the presence
of rejection and have low positive predictive values when compared to biopsy.
The current gold standard in detection of rejection is the use of endomyocardial biopsy.
Attaining these samples is invasive and long term repeated central venous access can be
difficult. Risk of endomyocardial biopsy includes perforation leading to cardiac tamponade,
arrhythmias including atrial fibrillation, pneumothorax, hemothorax, and valvular
regurgitation secondary to rupture of chordae or damage to valve leaflets themselves. There
is variability in pathological interpretation of histologic grades, especially at higher
grades of rejection due to the difficulty in interpretation of nodular infiltrates. The 2005
revised ISHLT grading system has simplified the grading system of cellular rejection and now
includes assessment of antibody mediated rejection. This may improve the utility of
endomyocardial biopsy, but much controversy still exists on the method of grading rejection
and its clinical implications. Thus, the development of a noninvasive, relatively inexpensive
method that accurately predicts the presence of rejection is critical.