Trial of Faropenem and Cefadroxil (in Combination With Amoxicillin/Clavulanic Acid and Standard TB Drugs) in Patients With Pulmonary Tuberculosis: Measurement of Early Bactericidal Activity and Effects on Novel Biomarkers
Condition: Pulmonary Tuberculosis
MeSH terms: Tuberculosis; Tuberculosis, Pulmonary
Study type: Interventional
Phase: Phase 2

Summary: 
      This trial aims to determine whether the early bactericidal activity of rifampicin given with
      faropenem or cefadroxil (each given with amoxicillin/clavulanic acid) is greater than the
      activity of rifampicin alone in patients with pulmonary TB. The trial will also investigate
      potential new biomarkers of sterilising activity.
    

Detailed description: 
      Tuberculosis (TB) remains one of the leading causes of mortality from an infectious disease
      worldwide with approximately 2 million deaths annually. There is an urgent need to identify
      new drugs, especially drugs with activity against persistent organisms that may enable
      shorter treatment regimens. Beta-lactam antibiotics have activity against TB in vitro and in
      animal models and there is evidence of synergy with rifampicin, one of the standard TB drugs.
      Amongst oral beta-lactam antibiotics, two appear to have optimal properties and optimal
      synergy with rifampicin and may be candidates for adjunctive treatment of drug-sensitive TB:
      faropenem (an oral penem, closely related to the carbapenem class) and cefadroxil (a first
      generation cephalosporin). Both drugs are used widely for the treatment of bacterial
      infections. They have in vitro activity against Mycobacterium tuberculosis, which is
      augmented when administered with rifampicin.

      This is a Phase II randomised, controlled, open-label, early bactericidal activity trial. We
      will recruit patients between the ages of 18 and 70 with newly-diagnosed smear positive
      pulmonary TB, who have not yet started TB therapy.

      Patients will be randomised into one of 3 arms to take faropenem (with amoxicillin/clavulanic
      acid) plus rifampicin, or cefadroxil (with amoxicillin/ clavulanic acid) plus rifampicin, or
      rifampicin alone for the first two days of the study. Patients will start standard TB therapy
      on the third day of the study and continue with the beta lactam antibiotics for the remaining
      5 days of the study. Following the completion of the 7 days of study medication, the study
      will end and patients will continue standard combination TB therapy under normal clinical
      follow-up.
    

Intervention name(s): Faropenem; Amoxicillin/clavulanic acid; Cefadroxil; Rifampicin
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Faropenem 600mg; Amoxicillin 500mg/ clavulanic acid 125mg; Cefadroxil 1g; Rifampicin 10mg/kg
Other intervention name(s): Farobact 200; Augmentin; Co-amoxiclav; Rifampin
Intervention MeSH terms: Amoxicillin; Rifampin; Amoxicillin-Potassium Clavulanate Combination; Clavulanic Acids; Clavulanic Acid; Cefadroxil
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Beta lactams; adjunctive therapy; drug-sensitive tuberculosis