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
| Verified date | February 2, 2010 |
| Source | National Institutes of Health Clinical Center (CC) |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Withdrawn |
| Enrollment | 0 |
| Est. completion date | February 2, 2010 |
| Est. primary completion date | February 2, 2010 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 20 Years and older |
| Eligibility |
- INCLUSION CRITERIA: Males and females age 20 and above. Subjects with treatment-refractory pulmonary TB (i.e., who remain sputum AFB smear positive and/or culture positive or who are sputum negative yet non-responsive by radiographic and clinical measures) (including MDR-TB) scheduled for elective pulmonary resection. Subjects who demonstrate one or more radiographic abnormalities associated with pulmonary tuberculosis (i.e., cavities, nodules, consolidation, fibrosis, or calcified lesions). Ability and willingness to utilize contraceptives (such as latex condom, diaphragm, cervical cap, IUD, hormonal contraception, tubal ligation, or vasectomy) from the time of consent to one month after the treatment period (both men and women). Ability and willingness to give written or oral informed consent. EXCLUSION CRITERIA: Subjects under the age of 20. Pregnant and breast-feeding women. Subjects with underlying neurological disease including seizure disorder and peripheral neuropathy. Subjects taking medications with a high incidence of central nervous system (CNS) toxicity (including cycloserine), within one week before or after the scheduled pimonidazole infusion or will be anticipated to need such drugs within one week after infusion. Subjects taking the following medications within one week before or will be anticipated to need such drugs after the scheduled infusion: oral anticoagulants, Cimetadine, Didasnosine, Disulfiram, Nisatidine, Ocytetracycline, Phenobarbital, or Phenytoin. Liver dysfunction with serum transaminases [AST (SGOT), ALT (SGPT)] and/or total bilirubin greater than 1.5 times ULN. Evidence of hepatitis as indicated by a positive HBV surface antigen test or a positive HCV antibody titer suggesting chronic infection. History of excessive alcohol use or alcohol abuse within the last year. Renal insufficiency with serum creatinine greater than 1.5 times ULN. Subjects assessed by the chest surgeon or surgery staff to be a high operative risk due to the presence of one or more underlying co-morbidities such as severe coronary artery disease, immunosuppression, or chronic obstructive pulmonary disease (COPD). Administration of any investigational test article within 30 days preceding the first dose of study drug. |
| Country | Name | City | State |
|---|---|---|---|
| Korea, Republic of | International Tuberculosis Research Center | Masan | |
| Korea, Republic of | National Masan Tuberculosis Hospital | Masan |
| Lead Sponsor | Collaborator |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) | International Tuberculosis Research Center |
Korea, Republic of,
Allen JG, Dische S, Lenox-Smith I, Malcolm SL, Saunders MI. The pharmacokinetics of a new radiosensitiser, Ro 03-8799 in humans. Eur J Clin Pharmacol. 1984;27(4):483-9. — View Citation
Durand RE, Raleigh JA. Identification of nonproliferating but viable hypoxic tumor cells in vivo. Cancer Res. 1998 Aug 15;58(16):3547-50. — View Citation
Kennedy AS, Raleigh JA, Perez GM, Calkins DP, Thrall DE, Novotny DB, Varia MA. Proliferation and hypoxia in human squamous cell carcinoma of the cervix: first report of combined immunohistochemical assays. Int J Radiat Oncol Biol Phys. 1997 Mar 1;37(4):897-905. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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. | Up to surgery. |