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Pimonidazole Hydrochloride to Detect Low Oxygen in Tuberculosis-Infected Lungs

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00374517
Recruitment Status : Withdrawn
First Posted : September 11, 2006
Last Update Posted : July 2, 2017
International Tuberculosis Research Center
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Refractory Pulmonary Tuberculosis Drug: Pimonidazole hydrochloride Phase 2

Detailed Description:

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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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
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
Study Start Date : September 5, 2006
Actual Primary Completion Date : February 2, 2010
Estimated Study Completion Date : February 2, 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Primary Outcome Measures :
  1. 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. ]

Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.


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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00374517

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Korea, Republic of
International Tuberculosis Research Center
Masan, Korea, Republic of
National Masan Tuberculosis Hospital
Masan, Korea, Republic of
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
International Tuberculosis Research Center

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Responsible Party: Clifton E. Barry III, Ph.D./National Institute of Allergy and Infectious Diseases, National Institutes of Health Identifier: NCT00374517     History of Changes
Other Study ID Numbers: 999906241
First Posted: September 11, 2006    Key Record Dates
Last Update Posted: July 2, 2017
Last Verified: February 2, 2010

Keywords provided by National Institutes of Health Clinical Center (CC):
Mycobacterium Tuberculosis
Pimonidazole Hydrochloride
Recurrent Tuberculosis
mRNA Expression
Pulmonary Tuberculosis

Additional relevant MeSH terms:
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Tuberculosis, Pulmonary
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections