Trial Outcomes & Findings for Metronidazole for Pulmonary Tuberculosis (South Korea) (NCT NCT00425113)

Last Updated: 2013-07-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

6 months.

Results posted on

2013-07-10

Participant Flow

Pulmonary multidrug-resistant tuberculosis subjects were recruited from the National Masan Hospital, Masan, South Korea from 2009-2010.

Participant milestones

Participant milestones
Measure	Metronidazole 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.	Placebo
Overall Study STARTED	17	18
Overall Study Exposed to Study Drug	16	17
Overall Study COMPLETED	15	16
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Metronidazole 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.	Placebo
Overall Study uncontrolled diabetes mellitus	1	0
Overall Study diagnosis of abdominal TB	0	1
Overall Study missing study drug more than 14 days	0	1
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Metronidazole for Pulmonary Tuberculosis (South Korea)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Metronidazole n=15 Participants 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.	Placebo n=16 Participants	Total n=31 Participants Total of all reporting groups
Age Continuous	36 years n=5 Participants	38 years n=7 Participants	37 years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	12 Participants n=7 Participants	25 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months.

Outcome measures

Outcome measures
Measure	Metronidazole n=15 Participants 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.	Placebo n=16 Participants
Changes in TB Lesion Sizes Using High Resolution Computed Tomography (HRCT). Baseline composite sum of all 10 features	8.11 reader score Standard Error 1.27	10.08 reader score Standard Error 1.00
Changes in TB Lesion Sizes Using High Resolution Computed Tomography (HRCT). Month 6 composite sum of all 10 features	6.64 reader score Standard Error 1.01	7.24 reader score Standard Error 0.89

SECONDARY outcome

Timeframe: 2 months

Outcome measures

Outcome measures
Measure	Metronidazole n=15 Participants 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.	Placebo n=16 Participants
Time to Sputum Culture Conversion to Negative on Solid Medium	21 days Interval 16.0 to 71.0	42.5 days Interval 15.0 to 69.0

Adverse Events

Metronidazole

Serious events: 9 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Metronidazole n=15 participants at risk 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.	Placebo n=16 participants at risk
Nervous system disorders peripheral neuropathy	26.7% 4/15 • Number of events 4	0.00% 0/16
Hepatobiliary disorders hepatitis	13.3% 2/15 • Number of events 2	0.00% 0/16
Nervous system disorders seizure	20.0% 3/15 • Number of events 3	6.2% 1/16 • Number of events 1
Infections and infestations aspergilloma	6.7% 1/15 • Number of events 1	0.00% 0/16
Respiratory, thoracic and mediastinal disorders hemoptysis	6.7% 1/15 • Number of events 1	0.00% 0/16
Skin and subcutaneous tissue disorders rash	0.00% 0/15	6.2% 1/16 • Number of events 1
Musculoskeletal and connective tissue disorders myalgia	0.00% 0/15	6.2% 1/16 • Number of events 1
Respiratory, thoracic and mediastinal disorders pneumothorax	0.00% 0/15	6.2% 1/16 • Number of events 1
Musculoskeletal and connective tissue disorders fracture	0.00% 0/15	6.2% 1/16 • Number of events 1
Gastrointestinal disorders gastritis	6.7% 1/15 • Number of events 2	0.00% 0/16

Other adverse events

Other adverse events
Measure	Metronidazole n=15 participants at risk 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.	Placebo n=16 participants at risk
General disorders hyperuricemia	40.0% 6/15 • Number of events 7	37.5% 6/16 • Number of events 6
Gastrointestinal disorders diarrhea	6.7% 1/15 • Number of events 1	6.2% 1/16 • Number of events 1
Gastrointestinal disorders nausea	6.7% 1/15 • Number of events 1	0.00% 0/16
Nervous system disorders peripheral neuropathy	26.7% 4/15 • Number of events 4	12.5% 2/16 • Number of events 2
Endocrine disorders hyperglycemia	13.3% 2/15 • Number of events 2	12.5% 2/16 • Number of events 2
General disorders hypokalemia	6.7% 1/15 • Number of events 1	0.00% 0/16
General disorders hypercholesterolemia	0.00% 0/15	6.2% 1/16 • Number of events 1

Additional Information

Ray Chen

National Institute of Allergy and Infectious Diseases

Phone: 301-443-5816

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place