The BLAST- 1 Trial - Cephalexin+Amoxicillin-clavulanate for Tuberculosis

• Status: Not yet recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The goal of this randomized controlled trial is to study the early bactericidal activity in adult patients with smear-positive pulmonary tuberculosis.

The main question it aims to answer are if cephalexin, in combination with amoxicillin-clavulanate, is effective in the treatment of tuberculosis.

Participants with smear-positive tuberculosis will be randomized to either of two groups:

Intervention group: cephalexin and amoxicillin-clavulanate. Control group: Standard of care TB treatment. The study period is 2 weeks and participants will be asked to submit multiple sputum samples to measure the bacterial sputum load. They will also submit saliva samples for estimation of drug concentrations in the body.

Researchers will compare the intervention group with the control group to see if the trial drugs result in a reduced bacterial sputum load

Overall aim: To study the early bactericidal activity of cephalexin, in combination with amoxicillin-clavulanate, in comparison to standard treatment in patients with active pulmonary tuberculosis during the first 2 weeks of treatment.

Primary aim:

1. To evaluate the early bactericidal activity (measured as 'time to culture positivity') of cephalexin-clavulanate in comparison, to standard TB treatment (rifampicin, isoniazid, pyrazinamide, and ethambutol).

Secondary aim:

2. To asses safety and tolerability of cephalexin together with amoxicillin-clavulanate.

3. To determine key pharmacokinetic (PK) parameters of cephalexin, especially half-life and drug exposure (maximal concentration; Cmax and area under the concentration versus time curve, AUC).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Western Sydney Local Health District
• Collaborator: Centre Of Research Excellence in Tuberculosis Control
• Treatments: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Cephalexin; Clavulanic Acid; Clavulanic Acids

Criteria

Inclusion Criteria:

• Consenting adults (≥18 years)

• ≥40 kg

• Smear-positive patients with active tuberculosis, confirmed by sputum smear, TB PCR and/or GeneXpert.

Exclusion Criteria:

• On TB treatment for >1 day

• Condition affecting ability of an informed consent (i.e. dementia, delirium etc).

• Pregnancy or breast-feeding

• HIV

• Known allergy or sensitivity to any of the study drugs

• Drug-resistant TB (resistance to rifampicin and/or isoniazid)

• Poor general condition or severe infection such that, in the opinion of the investigator at screening, any delay in initiation of definitive TB treatment cannot be tolerated

• TB with concomitant central nervous system and/or cardiac involvement.

• Any condition as determined by physical examination, medical history, laboratory data, or chest x-ray which, in the opinion of the investigator, would interfere with safety or endpoint assessments in the study.

• Use of metformin, probenecid or allopurinol

• Known previous Clostridium difficile infection due to the risk of colitis. (In case no medical records are available, it should be suspected in elderly patients reporting severe gastrointestinal infections in relation to courses of antibiotics)