Pimonidazole Hydrochloride to Detect Low Oxygen in Tuberculosis-Infected Lungs

NCT00374517 | Withdrawn Phase 2

• 2 other identifiers: 99990624106-I-N241
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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.

Conditions

Refractory Pulmonary Tuberculosis

Keywords

Mycobacterium Tuberculosis; Pimonidazole Hydrochloride; Recurrent Tuberculosis; Hypoxyprobe; mRNA Expression; Pulmonary Tuberculosis

Outcome Measures

Primary Outcomes (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.

  Up to surgery.

Interventions

Pimonidazole hydrochloride DRUG

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• International Tuberculosis Research Center: collaborator

Study Sites (2)

International Tuberculosis Research Center

Masan, South Korea

Location

National Masan Tuberculosis Hospital

Masan, South Korea

Location

Related Publications (3)

• 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. doi: 10.1007/BF00549599.

  PMID: 6519157 BACKGROUND

• Durand RE, Raleigh JA. Identification of nonproliferating but viable hypoxic tumor cells in vivo. Cancer Res. 1998 Aug 15;58(16):3547-50.

  PMID: 9721858 BACKGROUND

• 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. doi: 10.1016/s0360-3016(96)00539-1.

  PMID: 9128967 BACKGROUND

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: September 8, 2006
• First Posted: September 11, 2006
• Study Start: September 5, 2006
• Primary Completion: February 2, 2010
• Study Completion: February 2, 2010
• Last Updated: July 2, 2017

Record last verified: 2010-02-02

Locations

KR (2)