Pimonidazole Hydrochloride to Detect Low Oxygen in Tuberculosis-Infected Lungs

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborator:
NIAID, Korean Center for Disease Control and Prevention, International Tuberculosis Research Center, National Masan Tuberculosis Hospital
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00374517
First received: September 8, 2006
Last updated: November 16, 2011
Last verified: February 2010
  Purpose

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 Intervention Phase
Refractory Pulmonary Tuberculosis
Drug: Pimonidazole hydrochloride
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: September 2006
Estimated Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Pimonidazole hydrochloride
    N/A
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.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00374517

Locations
Korea, Republic of
National Masan Tuberculosis Hospital
Masan, Korea, Republic of
International Tuberculosis Research Center
Masan, Korea, Republic of
Sponsors and Collaborators
NIAID, Korean Center for Disease Control and Prevention, International Tuberculosis Research Center, National Masan Tuberculosis Hospital
  More Information

Publications:
Responsible Party: Clifton E. Barry III, Ph.D./National Institute of Allergy and Infectious Diseases, National Institutes of Health
ClinicalTrials.gov Identifier: NCT00374517     History of Changes
Other Study ID Numbers: 999906241, 06-I-N241
Study First Received: September 8, 2006
Last Updated: November 16, 2011
Health Authority: United States: Federal Government

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

Additional relevant MeSH terms:
Tuberculosis
Tuberculosis, Pulmonary
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Pimonidazole
Radiation-Sensitizing Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 27, 2014