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

NCT02381470 | Completed Phase 2 DMC

• 1 other identifier: Faropenem_TB
• Study Type: interventional
• Target: 58
• Locations: 3 countries
• Sites: 6

Brief 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.

Conditions

Pulmonary Tuberculosis

Keywords

Beta lactams; adjunctive therapy; drug-sensitive tuberculosis

Outcome Measures

Primary Outcomes (1)

• Rate of change of time to positivity (TTP) in liquid culture from day 0 to day 2

  2 days

Secondary Outcomes (3)

• Rate of change of TTP in liquid culture from day 0 to day 7

  7 days

• Change in CFU/ml in solid culture from Day 0 to Day 2

  2 days

• Change in CFU/ml in solid culture from Day 0 to Day 7

  7 days

Study Arms (3)

Faropenem

EXPERIMENTAL

Faropenem 600mg (with amoxicillin/clavulanic acid, 500mg/125mg) given three times daily for 7 days PLUS Rifampicin 10mg/kg once daily alone for the first 2 days then standard combination therapy (rifampicin, isoniazid, pyrazinamide, ethambutol, adjusted for body weight) for the following 5 days

Drug: Faropenem; Drug: Amoxicillin/clavulanic acid

Cefadroxil

EXPERIMENTAL

Cefadroxil 1g (with amoxicillin/clavulanic acid, 500mg/125mg) given twice daily for 7 days PLUS Rifampicin 10mg/kg once daily alone for the first 2 days then standard combination therapy (rifampicin, isoniazid, pyrazinamide, ethambutol, adjusted for body weight) for the following 5 days

Drug: Amoxicillin/clavulanic acid; Drug: Cefadroxil

Control

ACTIVE COMPARATOR

Rifampicin 10mg/kg once daily alone for the first 2 days then standard combination therapy (rifampicin, isoniazid, pyrazinamide, ethambutol, adjusted for body weight) for the following 5 days

Drug: Rifampicin

Interventions

Faropenem DRUG

Faropenem 600mg

Also known as: Farobact 200

Faropenem

Amoxicillin/clavulanic acid DRUG

Amoxicillin 500mg/ clavulanic acid 125mg

Also known as: Augmentin, Co-amoxiclav

Cefadroxil; Faropenem

Cefadroxil DRUG

Cefadroxil 1g

Cefadroxil

Rifampicin DRUG

Rifampicin 10mg/kg

Also known as: Rifampin

Control

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 70 years
• Clinical features compatible with pulmonary TB
• Sputum smear graded at least 1 +
• Estimated to be producing at least 5ml of sputum per day
• Willing to comply with study procedures and able to provide written informed consent.

You may not qualify if:

• Suspected miliary TB or TB meningitis
• Patients receiving any TB treatment within the previous 6 months
• Patients too ill to tolerate a 2-3 day delay in standard therapy
• Concurrent bacterial pneumonia
• Known hypersensitivity to beta-lactam drugs (penicillins, carbapenems) or rifampicin
• History of severe allergies or severe asthma
• Receiving loop diuretics
• Estimated creatinine clearance \< 80 ml/min on screening blood test
• ALT \> 2.5 times upper limit of normal on screening blood test.
• Presence of rifampicin resistance on GeneXpert (or alternative molecular test).
• Women who are currently pregnant or breastfeeding.
• Any other significant condition that would, in the opinion of the investigator, compromise the patient's safety or outcome in the trial.
• Participation in other clinical intervention trial or research protocol

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (6)

De La Salle Health Institute

Cavite, Philippines

Location

Tropical Disease Foundation

Makati City, Philippines

Location

Lung Center Philippines

Quezon City, Philippines

Location

National University Hospital, Singapore

Singapore, Singapore

Location

Infectious Diseases Institute

Kampala, Uganda

Location

Joint Clinical Research Centre

Kampala, Uganda

Location

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

fropenem; Amoxicillin-Potassium Clavulanate Combination; Cefadroxil; Rifampin

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Clavulanic Acid; Clavulanic Acids; beta-Lactams; Lactams; Amides; Organic Chemicals; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Cephalexin; Cephalosporins; Thiazines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Nicholas Paton

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2015
• First Posted: March 6, 2015
• Study Start: February 11, 2019
• Primary Completion: September 28, 2019
• Study Completion: October 2, 2019
• Last Updated: March 23, 2020

Record last verified: 2020-03

Locations

SG (1); UG (2); PH (3)