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

NCT05664568 | Unknown Phase 2

• 1 other identifier: 2022/PID01942
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief 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. 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).
2. 2.To asses safety and tolerability of cephalexin together with amoxicillin-clavulanate.
3. 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).

Conditions

Tuberculosis, Pulmonary

Keywords

Randomized controlled trial; Early bactericidal activity; Smear-positive TB; Betalactam antibiotics; Cephalosporin; Time to positivity

Outcome Measures

Primary Outcomes (1)

• Time to positivity (TTP)

  Early bactericidal activity measured as fall in time to positivity (TTP) 1\. The primary outcome is fall in bacterial load in sputum, measured as the rate of change in Time to Sputum Culture Positivity (TTP). TTP is the time to a positive culture when sputum samples are incubated in BACTEC MGIT for automated detection of M. tuberculosis. Measuring the fall in bacterial load is standard choice of outcome for studies evaluating the effect (kill) of drug on TB bacteria.

  2 weeks

Secondary Outcomes (3)

• Adverse events

  2 weeks

• Area under the concentration versus time curve (AUC) of cephalexin

  2 weeks

• Cmax of cephalexin

  2 weeks

Study Arms (2)

Standard of care TB

ACTIVE COMPARATOR

Standard of care treatment for TB (rifampicin, isoniazid, ethambutol and pyrazinamide according to WHO)

Other: Standard of care treatment of tuberculosis

Cephalexin + amoxicillin-clavulanate

EXPERIMENTAL

Intervention arm: cephalexin 1g thrice daily + amoxicillin-clavulanate 500/125 mg thrice daily.

Drug: Cephalexin; Drug: Amoxicillin-Clavulanate 500 Mg-125 Mg Oral Tablet

Interventions

Cephalexin DRUG

Participants in intervention group will receive a combination of cephalexin and amoxicillin-clavulanate for the first 2 weeks of TB treatment

Also known as: Keflex

Cephalexin + amoxicillin-clavulanate

Amoxicillin-Clavulanate 500 Mg-125 Mg Oral Tablet DRUG

Participants in the intervention group will receive a combination of cephalexin and amoxicillin-clavulanate for the first 2 weeks of TB treatment

Also known as: Augmentin

Cephalexin + amoxicillin-clavulanate

Standard of care treatment of tuberculosis OTHER

The control group will be given standard of care treatment of tuberculosis consisting of rifampicin, isoniazid, pyrazinamide and ethambutol

Also known as: HREZ

Standard of care TB

Eligibility Criteria

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

You may qualify if:

• Consenting adults (≥18 years)
• ≥40 kg
• Smear-positive patients with active tuberculosis, confirmed by sputum smear, TB PCR and/or GeneXpert.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Western Sydney Local Health District: lead
• Centre Of Research Excellence in Tuberculosis Control: collaborator

Study Sites (3)

Blacktown Hospital

Sydney, Australia

NOT YET RECRUITING

Royal Prince Alfred Hospital

Sydney, Australia

NOT YET RECRUITING

Western Sydney Health District

Sydney, Australia

RECRUITING

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

Cephalexin; Amoxicillin-Potassium Clavulanate Combination

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)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Clavulanic Acid; Clavulanic Acids; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Jan-Willem Alffenaar, Professor

  WSLHD, Department of Pharmacy, Westmead hospital, NSW, Australia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jan-Willem Alffenaar, Professor

CONTACT

+61 (0)286270019; johannes.alffenaar@nsw.health.gov.au

Lina Davies Forsman, MD, PhD

CONTACT

+61 (0)478384977

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Randomized-controlled early bactericidal activity trial

Study Record Dates

• First Submitted: November 2, 2022
• First Posted: December 23, 2022
• Study Start: March 15, 2023
• Primary Completion: July 1, 2024
• Study Completion: December 1, 2024
• Last Updated: June 26, 2023

Record last verified: 2023-06

Locations

AU (3)