Refractory Pulmonary Tuberculosis Clinical Trial
Official title:
A Phase II Clinical Trial of Pimonidazole Hydrochloride as a Hypoxia Marker in Subjects Undergoing Elective Lung Resection for Treatment-Refractory Pulmonary Tuberculosis
This study will determine whether a drug called pimonidazole hydrochloride shows areas of low
oxygen in tuberculosis (TB)-infected lungs. Pimonidazole is a "low oxygen marker," an agent
designed to find areas in the body that are not getting enough oxygen. If it is found that TB
grows where oxygen is low, these results may help doctors decide what medicines would be most
effective for treating TB.
Patients 20 years of age or older who are scheduled for lung surgery at the National Masan
Tuberculosis Hospital in Masan, Korea to treat their TB may be eligible for this study.
Participants undergo the following procedures:
- Blood draw before surgery to test for hepatitis B and hepatitis C viruses.
- Pregnancy test for women who can become pregnant.
- Infusion of pimonidazole through a vein in the arm 24 hours before surgery. A part of
the patient's lung is removed during surgery. This tissue is examined under a microscope
for evidence of pimonidazole, which would indicate low oxygen.
- Blood sample collection during surgery and on the 7th and 14th days after surgery to
check liver function.
The purpose of this Phase II clinical trial is to establish whether pulmonary tuberculous
lesions are hypoxic or contain hypoxic microenvironments using an in vivo hypoxia-imaging
marker, pimonidazole hydrochloride, in subjects undergoing lung resection surgery for
treatment-refractory pulmonary tuberculosis.
The study population will be drawn from subjects undergoing treatment at the National Masan
Tuberculosis Hospital (NMTH), Masan, Republic of Korea. Subjects who are scheduled for
partial lung resection surgery for treatment refractory TB will be eligible for this study.
Selected subjects will be those who demonstrate one or more radiographic abnormalities
associated with pulmonary tuberculosis (e.g., cavities, nodules, consolidation, fibrosis, or
calcified lesions).
Subjects undergoing elective pulmonary resection will receive a single preoperative IV dose
of pimonidazole 0.5 g/m(2) in 100 mL of normal saline, infused over 20 minutes 18 to 24 hours
prior to surgery. The resected tissue will be analyzed to look at the following: 1) the
degree of pimonidazole-adduct formation in tissue specimens with different histopathologic
presentations; 2) the number of acid-fast bacilli in tissue sections, smears, or cultures
prepared from homogenized lesions from distinct gross anatomic and histopathologic types in
relation to the extent of tissue hypoxia, and; 3) comparison of lesions labeling with
pimonidazole with the presence of human cellular and bacterial markers expected to be
expressed under oxygen-limiting conditions. NIAID study investigators will have no input of
any kind in selecting subjects for surgery, or in determining the kind or extent of surgical
resection. Subjects will be on study from a few days before surgery until approximately 8
weeks after their surgery.
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