The goal of this single-center, open-labelled, clinical trial in two groups aims to proof that a specific group of antibiotics (carbapenems) can be used to treat pulmonary tuberculosis if it is combined with another antibiotic (amoxicillin/clavulanate). A total of 113 male or female participants (8 groups and 9 treatment regimens as group 8 was split into 2 groups of 4 participants receiving Rifafour e-275), aged between 18 and 65 years (inclusive), with newly diagnosed, smear-positive, pulmonary TB.
The overall objective of this study is to evaluate the 2-week bactericidal activity and pharmacokinetics of the following beta-lactam containing combinations with the aim to select the most active and implementable solution to be incorporated into a drug-resistant TB combination regimen: * Once or twice daily meropenem administered intravenously in combination with once or twice daily oral amoxicillin/clavulanic acid; * Once daily ertapenem administered intravenously and intramuscularly in combination with twice daily oral amoxicillin/clavulanic acid; * Twice daily oral amoxicillin/clavulanic acid; * Once daily rifampicin administered orally at highest currently established dosage of 35mg/kg in combination with twice daily oral amoxicillin/clavulanic acid. A single-center, open-labeled, clinical trial in two groups. The treatments are: Group 1: 1. Meropenem 6g intravenously once daily; plus amoxicillin/CA 2 x 1000mg/62.5mg orally 12-hourly on days 1-14. 2. Ertapenem 1g intramuscularly once daily; plus amoxicillin/CA 2 x 1000mg/62.5mg orally 12-hourly on days 1-14. Group 2: 3. Meropenem 3g intravenously twice daily; plus amoxicillin/CA 2 x 1000mg/62.5mg orally 12-hourly on days 1-14. 4. Ertapenem 1g intravenously once daily; plus amoxicillin/CA 2 x 1000mg/62.5mg orally 12-hourly on days 1-14. 5. Amoxicillin/CA 2 x 1000mg/62.5mg orally 12-hourly on days 1-14. 6. Rifampicin 35 mg/kg once daily; plus amoxicillin/CA 2 x 1000mg/62.5mg orally 12-hourly on days 1-14. 7. Meropenem 6g OR meropenem 4g intravenously once daily; plus amoxicillin/CA 2 x 1000mg/62.5mg orally once daily on days 1-14. A total of 4 participants per group will receive standard first line TB treatment as per the South African TB guidelines (Rifafour e-275) and is included as a control for the EBA quantitative mycobacteriology and to evaluate whether HRZE gives similar EBA results to that demonstrated in prior studies with this combination. The mycobacteriology laboratory will remain blinded until closure of the EBA results. Enrollment into group 1 will be completed before enrollment into group 2 will start. After completion of enrollment into group 1, there will be an interim analysis while enrollment into group 2 is ongoing.
Study Type
Meropenem 6g intravenously over 6 hours once daily on days 1-14.
Ertapenem 1g intramuscularly once daily on days 1-14.
Meropenem 3g intravenously twice daily over 60 minutes on days 1-14.
TASK Clinical Research Centre
Cape Town, Western Cape, South Africa
Early bactericidal activity by change in logCFU over 14 days
The EBACFU(0-14) as determined by the rate of change in logCFU (colony forming units) per ml sputum over the period Day 0 to Day 14 which will be summarised and described with a statistical model as an estimated average decrease per day for patients in each group.
Time frame: 14 days
Early bactericidal activity by change in time-to-positivity over 14 days
The EBATTP(0-14) as determined by the percentage rate of change in TTP (time to positivity) per ml sputum over the period Day 0 to Day 14, which will be summarised and described with a statistical model as an estimated average increase per day for patients in each group.
Time frame: 14 days
Early bactericidal activity by change in logCFU and TTP per ml over 0-2 days, 0-7 days, and 2-14 days
Drug activity with CFU or TTP over different treatment periods such as 0-2 days, 0-7 days, and 2-14 days as indicated, for cross-comparison with other published data.
Time frame: 0-2 days, 0-7 days, 2-14 days
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INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
134
Ertapenem 1g intravenously once daily on days 1-14.
Amoxicillin/CA 2 tablets x 1000mg/62.5mg orally 12-hourly on days 1-14.
Rifampicin 35 mg/kg once daily on days 1-14.
Meropenem 6g intravenously once daily over 60 minutes on days 1-14.
Rifafour e-275 will be supplied as fixed dose combination tablets and administered orally once daily for 14 days as The daily dose is dependent on the participants' weight as follows: 40 - 54kg: 3 tablets; 55 - 70kg: 4 tablets; 71kg and over: 5 tablets.
Meropenem 4g intravenously once daily over 60 minutes on days 1-14.
Amoxicillin/CA 2 tablets x 1000mg/62.5mg orally once daily on days 1-14.