Comparison of the Quantiferon®-TB GOLD (in Tube) Assay With Tuberculin Skin Testing for Detecting Latent Tuberculosis Infection in Patients With Chronic Liver Disease Being Evaluated for or Awaiting Liver Transplantation
| Status: | Withdrawn |
|---|---|
| Conditions: | Infectious Disease, Gastrointestinal |
| Therapuetic Areas: | Gastroenterology, Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | January 2007 |
Tuberculosis (TB) is an important cause of morbidity and mortality in organ transplant
recipients. Management of tuberculosis in this setting is challenging due to the complexity
of diagnosis and the potential toxicity of anti-TB therapy, especially in liver transplant
candidates and recipients. Although the tuberculin skin test (TST) is recommended for
screening of latent tuberculosis infection (LTBI) in all candidates for liver
transplantation, the performance of the TST in this setting is less than optimal, due to a
lack of specificity (false-positive results due to interaction with BCG vaccine and other
mycobacterial infections), and a lack of sensitivity in a population that is relatively
immunocompromised. Recently, a new test named QuantiFERON-TB Gold (QFT-G) has been approved
for the diagnosis of LTBI. QFT-G detects the release of interferon-gamma (IFN-γ) by
sensitized white cells after incubation of whole blood with TB antigens. QFT-G is expected
to be more specific than TST. However, there are no studies defining the performance of
QFT-G in a population of patients on a waiting list for liver transplantation. We plan to
estimate the usefulness of the QFT-G test for the diagnosis of LTBI in a cohort of patients
with end-stage liver disease. We hypothesize that the QFT-G test will correlate better with
the risk of LTBI. This study advances research on the prevention of a serious bacterial
infection that can have devastating consequences in the post-transplant setting. The new
diagnostic strategy may more accurately determine the presence of LTBI, thereby allowing
appropriate therapy.
recipients. Management of tuberculosis in this setting is challenging due to the complexity
of diagnosis and the potential toxicity of anti-TB therapy, especially in liver transplant
candidates and recipients. Although the tuberculin skin test (TST) is recommended for
screening of latent tuberculosis infection (LTBI) in all candidates for liver
transplantation, the performance of the TST in this setting is less than optimal, due to a
lack of specificity (false-positive results due to interaction with BCG vaccine and other
mycobacterial infections), and a lack of sensitivity in a population that is relatively
immunocompromised. Recently, a new test named QuantiFERON-TB Gold (QFT-G) has been approved
for the diagnosis of LTBI. QFT-G detects the release of interferon-gamma (IFN-γ) by
sensitized white cells after incubation of whole blood with TB antigens. QFT-G is expected
to be more specific than TST. However, there are no studies defining the performance of
QFT-G in a population of patients on a waiting list for liver transplantation. We plan to
estimate the usefulness of the QFT-G test for the diagnosis of LTBI in a cohort of patients
with end-stage liver disease. We hypothesize that the QFT-G test will correlate better with
the risk of LTBI. This study advances research on the prevention of a serious bacterial
infection that can have devastating consequences in the post-transplant setting. The new
diagnostic strategy may more accurately determine the presence of LTBI, thereby allowing
appropriate therapy.
- Review and record the results of the test/procedures (x-rays, CT-scans, etc.) that are
part of the subject's clinical care and the results will become part of the research
record. In addition, laboratory results (liver function tests, chemistry, CBC with
diff, PT and INR or PTT) will be collected from the medical record.
- Record the list of medications the subject is taking. Collect information on
demographics (address, phone number, etc.) including gender, race and ethnicity.
- Review and record past medical and social history
The screening procedures will take a total of about 15-30 minutes and all subjects will be
seen in the Liver Transplant Clinic. The investigator and research coordinators will be
reviewing the subject's medical record to collect the required information about the
subject's medical history. We will ask the subject, if it cannot be found in the medical
record, about past TB exposure and treatment, overseas travel, and current resident status
(long term care facility, home, hospital, etc.)
If the subject qualifies for the research study the subject will undergo the experimental
procedures listed below. These procedures will take place during the visit in the Liver
Transplant Clinic.
As part of the liver transplant evaluation subjects will have blood withdrawn for different
types of testing. When the blood is obtained we will collect about 3cc of blood for the new
TB testing. This collection of the blood sample will occur while the subject is getting
their required pre transplant blood work so that they will not need to get stuck twice with
a needle. The results of this research testing will not be available to the subject or
physicians but will be compared.
The QuantiFERON®-TB Gold IT system uses specialized blood collection tubes, which are used
to collect whole blood. Incubation of the blood occurs in the tubes for 16 to 24 hours,
after which, plasma is harvested and tested for the presence of IFN-g produced in response
to the peptide antigens.
The QFT-G (IT) assay will be performed according to the manufacturer's instructions
(Cellestis Ltd.). One mL of whole blood is placed in three separate test tubes, one
containing no antigen (nil control), one with TB antigens (ESAT-6, CFP-10 and TB7.7) and one
with phytohemaglutinin (mitogen or positive control). The three tubes will be incubated as
soon as possible after collection (within 16hrs) and will incubate for 16 to 24 hours at
37°C. Following this incubation period, the tubes will be centrifuged. The plasma will be
removed from the tube and placed in a plasma storage container. These containers will then
be frozen for future IFN-γ measurement by ELISA. Each institution will perform testing up to
this point in the process. Each month, plasma samples will be posted on ice to Edmonton
Hospital in Alberta, Canada. The samples will be batched and then undergo the ELISA testing
process according to the manufacturer's instructions.
A result of ≥0.35 IU/mL in the TB antigen tube will be considered a positive result. If the
level is less than this and the mitogen control is positive (≥ 0.5 IU/mL), a negative result
will be recorded. If the level in both the TB antigen and mitogen tube is less than the
threshold for positive, then an indeterminate (anergic) result will be recorded. The nil
antigen tube adjusts for background IFN-γ levels and is subtracted from the IFN-γ level for
the TB antigen and mitogen tube.
Once we have collected the blood sample the subject will have completed the study.
part of the subject's clinical care and the results will become part of the research
record. In addition, laboratory results (liver function tests, chemistry, CBC with
diff, PT and INR or PTT) will be collected from the medical record.
- Record the list of medications the subject is taking. Collect information on
demographics (address, phone number, etc.) including gender, race and ethnicity.
- Review and record past medical and social history
The screening procedures will take a total of about 15-30 minutes and all subjects will be
seen in the Liver Transplant Clinic. The investigator and research coordinators will be
reviewing the subject's medical record to collect the required information about the
subject's medical history. We will ask the subject, if it cannot be found in the medical
record, about past TB exposure and treatment, overseas travel, and current resident status
(long term care facility, home, hospital, etc.)
If the subject qualifies for the research study the subject will undergo the experimental
procedures listed below. These procedures will take place during the visit in the Liver
Transplant Clinic.
As part of the liver transplant evaluation subjects will have blood withdrawn for different
types of testing. When the blood is obtained we will collect about 3cc of blood for the new
TB testing. This collection of the blood sample will occur while the subject is getting
their required pre transplant blood work so that they will not need to get stuck twice with
a needle. The results of this research testing will not be available to the subject or
physicians but will be compared.
The QuantiFERON®-TB Gold IT system uses specialized blood collection tubes, which are used
to collect whole blood. Incubation of the blood occurs in the tubes for 16 to 24 hours,
after which, plasma is harvested and tested for the presence of IFN-g produced in response
to the peptide antigens.
The QFT-G (IT) assay will be performed according to the manufacturer's instructions
(Cellestis Ltd.). One mL of whole blood is placed in three separate test tubes, one
containing no antigen (nil control), one with TB antigens (ESAT-6, CFP-10 and TB7.7) and one
with phytohemaglutinin (mitogen or positive control). The three tubes will be incubated as
soon as possible after collection (within 16hrs) and will incubate for 16 to 24 hours at
37°C. Following this incubation period, the tubes will be centrifuged. The plasma will be
removed from the tube and placed in a plasma storage container. These containers will then
be frozen for future IFN-γ measurement by ELISA. Each institution will perform testing up to
this point in the process. Each month, plasma samples will be posted on ice to Edmonton
Hospital in Alberta, Canada. The samples will be batched and then undergo the ELISA testing
process according to the manufacturer's instructions.
A result of ≥0.35 IU/mL in the TB antigen tube will be considered a positive result. If the
level is less than this and the mitogen control is positive (≥ 0.5 IU/mL), a negative result
will be recorded. If the level in both the TB antigen and mitogen tube is less than the
threshold for positive, then an indeterminate (anergic) result will be recorded. The nil
antigen tube adjusts for background IFN-γ levels and is subtracted from the IFN-γ level for
the TB antigen and mitogen tube.
Once we have collected the blood sample the subject will have completed the study.
Inclusion Criteria
- Age ≥ 18
- Chronic liver disease on the waiting list or being wait listed for liver
transplantation
- Undergoing a PPD test as part of their clinical care
Exclusion Criteria
- Unable to provide informed consent
- Previous history of immediate hypersensitivity to TST
- Previous severe local ulceration with TST
- Suspected active TB
We found this trial at
1
site
University of Pittsburgh Medical Center UPMC is one of the leading nonprofit health systems in...
Click here to add this to my saved trials
