NCT05896930

Study to Evaluate EBA, Safety and Tolerability of Carbapenems in Adults With Pulmonary Tuberculosis

Phase 2 Trial to Evaluate the Early EBA, Safety and Tolerability of Amoxicillin/Clavulanate With or Without Meropenem, Ertapenem or Rifampicin in Adults With Newly Diagnosed, Smear-Positive Rifampicin-Susceptible Pulmonary Tuberculosis

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 134 (actual)
• Sponsor: TASK Applied Science · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Pulmonary Tuberculosis

Interventions

Type	Name	Description
DRUG	Meropenem 6g IV over 6 hours	Meropenem 6g intravenously over 6 hours once daily on days 1-14.
DRUG	Ertapenem 1g IM	Ertapenem 1g intramuscularly once daily on days 1-14.
DRUG	Meropenem 3g IV	Meropenem 3g intravenously twice daily over 60 minutes on days 1-14.
DRUG	Ertapenem 1g IV	Ertapenem 1g intravenously once daily on days 1-14.
DRUG	Amoxicillin/CA twice daily	Amoxicillin/CA 2 tablets x 1000mg/62.5mg orally 12-hourly on days 1-14.
DRUG	Rifampicin 35 mg/kg	Rifampicin 35 mg/kg once daily on days 1-14.
DRUG	Meropenem 6g IV over 60 minutes	Meropenem 6g intravenously once daily over 60 minutes on days 1-14.
DRUG	Rifafour e-275	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.
DRUG	Meropenem 4g IV	Meropenem 4g intravenously once daily over 60 minutes on days 1-14.
DRUG	Amoxicillin/CA once daily	Amoxicillin/CA 2 tablets x 1000mg/62.5mg orally once daily on days 1-14.

Timeline

• Start date: 2017-11-09
• Primary completion: 2021-01-04
• Completion: 2021-01-04
• First posted: 2023-06-09
• Last updated: 2023-06-09

Locations

1 site across 1 country: South Africa