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Metronidazole for Pulmonary Tuberculosis (South Korea)

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ClinicalTrials.gov Identifier: NCT00425113
Recruitment Status : Completed
First Posted : January 22, 2007
Results First Posted : July 10, 2013
Last Update Posted : July 10, 2013
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Tuberculosis
Multi-Drug Resistant Tuberculosis
Interventions Drug: Metronidazole
Procedure: Blood Draw
Procedure: CT Scan
Procedure: PET Scan
Enrollment 35
Recruitment Details Pulmonary multidrug-resistant tuberculosis subjects were recruited from the National Masan Hospital, Masan, South Korea from 2009-2010.
Pre-assignment Details  
Arm/Group Title Metronidazole Placebo
Hide Arm/Group Description Subjects were randomized to receive metronidazole 500 mg TID or placebo for 8 weeks, in addition to an individualized background TB treatment regimen. Total duration of treatment was about 18 months following sputum culture conversion. [Not Specified]
Period Title: Overall Study
Started 17 18
Exposed to Study Drug 16 17
Completed 15 [1] 16 [1]
Not Completed 2 2
Reason Not Completed
uncontrolled diabetes mellitus             1             0
diagnosis of abdominal TB             0             1
missing study drug more than 14 days             0             1
Withdrawal by Subject             1             0
[1]
Included in modified intent-to-treat analysis
Arm/Group Title Metronidazole Placebo Total
Hide Arm/Group Description Subjects were randomized to receive metronidazole 500 mg TID or placebo for 8 weeks, in addition to an individualized background TB treatment regimen. Total duration of treatment was about 18 months following sputum culture conversion. [Not Specified] Total of all reporting groups
Overall Number of Baseline Participants 15 16 31
Hide Baseline Analysis Population Description
2 subjects excluded: 1 for uncontrolled diabetes mellitus and 1 for diagnosis of extrapulmonary TB. 2 additional subjects withdrew: 1 self- withdrew and the other was withdrawn for missing >14 days of study drug.
Age Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 15 participants 16 participants 31 participants
36
(28 to 39)
38
(31 to 44)
37
(30 to 43)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 16 participants 31 participants
Female
2
  13.3%
4
  25.0%
6
  19.4%
Male
13
  86.7%
12
  75.0%
25
  80.6%
1.Primary Outcome
Title Changes in TB Lesion Sizes Using High Resolution Computed Tomography (HRCT).
Hide Description Lesions were defined as nodules (<2 mm, 2-<4 mm, and 4-10 mm), consolidations, collapse, cavities, fibrosis, bronchial thickening, tree-in-bud opacities, and ground glass opacities. Each CT was divided into six zones (upper, middle, and lower zones of the right and left lungs) and independently scored for the above lesions by three separate radiologists blinded to treatment arm. A fourth radiologist adjudicated any scores that were widely discrepant among the initial three radiologists. The HRCT score was determined by visually estimating the extent of the above lesions in each lung zone as follows: 0=0% involvement; 1= 1-25% involvement; 2=26-50% involvement; 3=51-75% involvement; and 4=76-100% involvement. A composite score for each lesion was calculated by adding the score for each specific abnormality in the 6 lung zones and dividing by 6, with the change in composite score measured at 2 and 6 months compared to baseline. Composite sums of all 10 composite scores are reported.
Time Frame 6 months.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Metronidazole Placebo
Hide Arm/Group Description:
Subjects were randomized to receive metronidazole 500 mg three times daily or placebo for 8 weeks, in addition to an individualized background TB treatment regimen. Total duration of treatment was about 18 months following sputum culture conversion.
[Not Specified]
Overall Number of Participants Analyzed 15 16
Mean (Standard Error)
Unit of Measure: reader score
Baseline composite sum of all 10 features 8.11  (1.27) 10.08  (1.00)
Month 6 composite sum of all 10 features 6.64  (1.01) 7.24  (0.89)
2.Secondary Outcome
Title Time to Sputum Culture Conversion to Negative on Solid Medium
Hide Description [Not Specified]
Time Frame 2 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Metronidazole Placebo
Hide Arm/Group Description:
Subjects were randomized to receive metronidazole 500 mg TID or placebo for 8 weeks, in addition to an individualized background TB treatment regimen. Total duration of treatment was about 18 months following sputum culture conversion.
[Not Specified]
Overall Number of Participants Analyzed 15 16
Median (95% Confidence Interval)
Unit of Measure: days
21
(16 to 71)
42.5
(15 to 69)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Metronidazole Placebo
Hide Arm/Group Description Subjects were randomized to receive metronidazole 500 mg TID or placebo for 8 weeks, in addition to an individualized background TB treatment regimen. Total duration of treatment was about 18 months following sputum culture conversion. [Not Specified]
All-Cause Mortality
Metronidazole Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Metronidazole Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/15 (60.00%)      4/16 (25.00%)    
Gastrointestinal disorders     
gastritis  1/15 (6.67%)  2 0/16 (0.00%)  0
Hepatobiliary disorders     
hepatitis  2/15 (13.33%)  2 0/16 (0.00%)  0
Infections and infestations     
aspergilloma  1/15 (6.67%)  1 0/16 (0.00%)  0
Musculoskeletal and connective tissue disorders     
myalgia  0/15 (0.00%)  0 1/16 (6.25%)  1
fracture  0/15 (0.00%)  0 1/16 (6.25%)  1
Nervous system disorders     
peripheral neuropathy  4/15 (26.67%)  4 0/16 (0.00%)  0
seizure  3/15 (20.00%)  3 1/16 (6.25%)  1
Respiratory, thoracic and mediastinal disorders     
hemoptysis  1/15 (6.67%)  1 0/16 (0.00%)  0
pneumothorax  0/15 (0.00%)  0 1/16 (6.25%)  1
Skin and subcutaneous tissue disorders     
rash  0/15 (0.00%)  0 1/16 (6.25%)  1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Metronidazole Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/15 (73.33%)      8/16 (50.00%)    
Endocrine disorders     
hyperglycemia  2/15 (13.33%)  2 2/16 (12.50%)  2
Gastrointestinal disorders     
diarrhea  1/15 (6.67%)  1 1/16 (6.25%)  1
nausea  1/15 (6.67%)  1 0/16 (0.00%)  0
General disorders     
hyperuricemia  6/15 (40.00%)  7 6/16 (37.50%)  6
hypokalemia  1/15 (6.67%)  1 0/16 (0.00%)  0
hypercholesterolemia  0/15 (0.00%)  0 1/16 (6.25%)  1
Nervous system disorders     
peripheral neuropathy  4/15 (26.67%)  4 2/16 (12.50%)  2
Major limitation of our study was the small sample size. Planned enrollment was 80 subjects but DSMB recommended closing the study to new enrollment after 35 subjects due to increased peripheral neuropathy in the metronidazole arm.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Ray Chen
Organization: National Institute of Allergy and Infectious Diseases
Phone: 301-443-5816
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier: NCT00425113     History of Changes
Other Study ID Numbers: 999907041
07-I-N041
First Submitted: January 19, 2007
First Posted: January 22, 2007
Results First Submitted: February 7, 2013
Results First Posted: July 10, 2013
Last Update Posted: July 10, 2013