Pimonidazole Hydrochloride to Detect Low Oxygen in Tuberculosis-Infected Lungs
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.
|Refractory Pulmonary Tuberculosis||Drug: Pimonidazole hydrochloride||Phase 2|
|Study Design:||Primary Purpose: Treatment|
|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|
- Frequency of pimonidazole labeling in specific lesion types within resected lung specimens and the frequency of co-localization of AFB positive bacilli with pimonidazole regions in lesions. [ Time Frame: Up to surgery. ]
|Study Start Date:||September 5, 2006|
|Estimated Study Completion Date:||February 2, 2010|
|Primary Completion Date:||February 2, 2010 (Final data collection date for primary outcome measure)|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00374517
|Korea, Republic of|
|International Tuberculosis Research Center|
|Masan, Korea, Republic of|
|National Masan Tuberculosis Hospital|
|Masan, Korea, Republic of|