Ignite Creation Date:
2024-05-05 @ 5:18 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00425113
Status:
COMPLETED
Last Update Posted:
2013-07-10
First Post:
2007-01-19
Brief Title:
Metronidazole for Pulmonary Tuberculosis South Korea
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Randomized Double-Blind Placebo-Controlled Phase II Study of Metronidazole Combined With Antituberculous Chemotherapy vs Antituberculous Chemotherapy With Placebo in Subjects With Multi-Drug Resistant Pulmonary Tuberculosis
Status:
COMPLETED
Status Verified Date:
2013-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will evaluate the effect of adding metronidazole to standard second-line therapy for tuberculosis in patients who have multi-drug resistant tuberculosis MDR-TB of the lungs It will evaluate the safety and tolerability of metronidazole in combination with antituberculosis agents Metronidazole is a drug widely used to treat bacterial and parasitic infections occurring in environments with very little oxygen such as the human colon Nine million new cases of sputum-positive tuberculosis are diagnosed worldwide each year
Patients ages 20 and older who have symptoms of TB who have been treated for tuberculosis but whose disease is multi-drug resistant and who are not pregnant or breast feeding may be eligible for this study They will be recruited in the National Masan Tuberculosis Hospital NMTH Masan Republic of Korea Patients will undergo the following tests and procedures
Collection of sputum for counting of bacteria
Drawing of blood for routine blood chemistry analysis for measuring levels of metronidazole TB lipid analysis and for testing levels of T-cells which are part of an immune response
Two targeted positron emission tomography PET scans each with a computed tomography CT scan and five high-resolution CT scans
Patients will receive either an 8-week course of standard second-line agents plus placebo sugar pill or an 8-week course of standard agents plus metronidazole The subjects doctors and researchers will not know which patients are taking the metronidazole until after the first 2 years of the trial A total of 60 patients will be assigned to two cohorts of 30 patients each After 8 weeks all patients will return to the standard of care chemotherapy according to normal procedures at NMTH
Side effects of metronidazole commonly reported are vaginal discharge symptoms of Candida cervicitis and vaginitis headache nausea and vomiting and dizziness Peripheral neuropathy an abnormal condition of the nerves may also be a side effect The precise incidence of neuropathy is unknown but is usually related to the duration of metronidazole use It can almost always be reversed when the drug is discontinued Serious side effects though rare may include leukopenia and thrombocytopenia disorders in the blood seizures and other central nervous system problems and hepatitis
This study may or may not have a direct benefit for participants However it is possible that patients drug-resistant disease may be more effectively treated as a result of metronidazole The study may help identify new methods for measuring drug effectiveness during TB studies
Patients ages 20 and older who have symptoms of TB who have been treated for tuberculosis but whose disease is multi-drug resistant and who are not pregnant or breast feeding may be eligible for this study They will be recruited in the National Masan Tuberculosis Hospital NMTH Masan Republic of Korea Patients will undergo the following tests and procedures
Collection of sputum for counting of bacteria
Drawing of blood for routine blood chemistry analysis for measuring levels of metronidazole TB lipid analysis and for testing levels of T-cells which are part of an immune response
Two targeted positron emission tomography PET scans each with a computed tomography CT scan and five high-resolution CT scans
Patients will receive either an 8-week course of standard second-line agents plus placebo sugar pill or an 8-week course of standard agents plus metronidazole The subjects doctors and researchers will not know which patients are taking the metronidazole until after the first 2 years of the trial A total of 60 patients will be assigned to two cohorts of 30 patients each After 8 weeks all patients will return to the standard of care chemotherapy according to normal procedures at NMTH
Side effects of metronidazole commonly reported are vaginal discharge symptoms of Candida cervicitis and vaginitis headache nausea and vomiting and dizziness Peripheral neuropathy an abnormal condition of the nerves may also be a side effect The precise incidence of neuropathy is unknown but is usually related to the duration of metronidazole use It can almost always be reversed when the drug is discontinued Serious side effects though rare may include leukopenia and thrombocytopenia disorders in the blood seizures and other central nervous system problems and hepatitis
This study may or may not have a direct benefit for participants However it is possible that patients drug-resistant disease may be more effectively treated as a result of metronidazole The study may help identify new methods for measuring drug effectiveness during TB studies
Detailed Description:
BACKGROUND
Despite significant in vitro data that metronidazole is active against Mycobacterium tuberculosis MTB maintained under anaerobic conditions the utility of this agent has not been evaluated carefully in human disease due to lack of efficacy in murine models of tuberculosis TB Unlike disease in rodents however human disease is characterized by discrete types of lesions including both aerobic cavities and anaerobic caseous necrotic nodules areas Recent experiments in non-human primates have demonstrated that closed caseous necrotic lesions are highly anoxic and are therefore likely to contain anaerobic bacilli highly susceptible to metronidazole Recent studies in TB-infected rabbits have shown that metronidazole therapy is highly effective in an animal model that recapitulates this feature of human disease Both of these studies support the possibility that metronidazole may have unique activity against an anaerobic sub-population of bacilli in human disease Such sub-populations may be responsible for the extended duration of chemotherapy typically employed in tuberculosis chemotherapy as anoxic bacteria are highly resistant to the sterilizing effects of front-line tuberculosis agents One small clinical trial of metronidazole in an Indian population also suggests that this agent may have a significant unappreciated role in the control of human tuberculosis
AIMS
The major aim of this study is to evaluate the ability of metronidazole to kill an anaerobic sub-population of Mycobacterium tuberculosis within multi-drug resistant tuberculosis MDR-TB patients In order to address this sub-population in the context of disease this study combines traditional measurements of drug efficacy including the rate of sputum clearance of organisms with a functional imaging technique 18 F-fluoro-2-deoxy-D-glucose -positron emission tomography - high-resolution computed tomography FDG-PET-HRCT that has not previously been applied to monitoring tuberculosis chemotherapy In addition this clinical trial will evaluate the tolerability and preliminary efficacy of metronidazole 500 mg three times a day tid when given in combination with standard second-line antituberculous treatment
METHODS
Type of study to be conducted
Randomized double-blinded placebo controlled phase II study
Population to be Studied
The study population will be drawn from subjects at the National Masan Tuberculosis Hospital NMTH Changwon Republic of Korea Subjects presenting at NMTH who have been previously treated with first-line agents and who are multi-drug resistant MDR defined as having TB isolates that are resistant to at least isoniazid and rifampicin and are therefore eligible for second-line antituberculous drug therapy will be included
Treatment Regimen and Treatment Periods
All patients will receive either 1 an 8-week course of standard second-line agents plus placebo tid or 2 an 8-week course of standard second-line agents plus 500 mg tid metronidazole In total sixty subjects will be accrued into two cohorts of 30 patients each After 8 weeks all subjects will revert to standard of care SOC chemotherapy according to normal procedures at NMTH According to hospital standard of care patients are continued on second-line medications for 18-24 months following sputum culture conversion
Despite significant in vitro data that metronidazole is active against Mycobacterium tuberculosis MTB maintained under anaerobic conditions the utility of this agent has not been evaluated carefully in human disease due to lack of efficacy in murine models of tuberculosis TB Unlike disease in rodents however human disease is characterized by discrete types of lesions including both aerobic cavities and anaerobic caseous necrotic nodules areas Recent experiments in non-human primates have demonstrated that closed caseous necrotic lesions are highly anoxic and are therefore likely to contain anaerobic bacilli highly susceptible to metronidazole Recent studies in TB-infected rabbits have shown that metronidazole therapy is highly effective in an animal model that recapitulates this feature of human disease Both of these studies support the possibility that metronidazole may have unique activity against an anaerobic sub-population of bacilli in human disease Such sub-populations may be responsible for the extended duration of chemotherapy typically employed in tuberculosis chemotherapy as anoxic bacteria are highly resistant to the sterilizing effects of front-line tuberculosis agents One small clinical trial of metronidazole in an Indian population also suggests that this agent may have a significant unappreciated role in the control of human tuberculosis
AIMS
The major aim of this study is to evaluate the ability of metronidazole to kill an anaerobic sub-population of Mycobacterium tuberculosis within multi-drug resistant tuberculosis MDR-TB patients In order to address this sub-population in the context of disease this study combines traditional measurements of drug efficacy including the rate of sputum clearance of organisms with a functional imaging technique 18 F-fluoro-2-deoxy-D-glucose -positron emission tomography - high-resolution computed tomography FDG-PET-HRCT that has not previously been applied to monitoring tuberculosis chemotherapy In addition this clinical trial will evaluate the tolerability and preliminary efficacy of metronidazole 500 mg three times a day tid when given in combination with standard second-line antituberculous treatment
METHODS
Type of study to be conducted
Randomized double-blinded placebo controlled phase II study
Population to be Studied
The study population will be drawn from subjects at the National Masan Tuberculosis Hospital NMTH Changwon Republic of Korea Subjects presenting at NMTH who have been previously treated with first-line agents and who are multi-drug resistant MDR defined as having TB isolates that are resistant to at least isoniazid and rifampicin and are therefore eligible for second-line antituberculous drug therapy will be included
Treatment Regimen and Treatment Periods
All patients will receive either 1 an 8-week course of standard second-line agents plus placebo tid or 2 an 8-week course of standard second-line agents plus 500 mg tid metronidazole In total sixty subjects will be accrued into two cohorts of 30 patients each After 8 weeks all subjects will revert to standard of care SOC chemotherapy according to normal procedures at NMTH According to hospital standard of care patients are continued on second-line medications for 18-24 months following sputum culture conversion
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 07-I-N041 | None | None | None |