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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05664568




Registration number
NCT05664568
Ethics application status
Date submitted
2/11/2022
Date registered
23/12/2022
Date last updated
26/06/2023

Titles & IDs
Public title
The BLAST- 1 Trial - Cephalexin+Amoxicillin-clavulanate for Tuberculosis
Scientific title
Early Bactericidal Activity of Cephalexin and Amoxicillin-clavulanate for Susceptible Tuberculosis - BLAST 1 Trial
Secondary ID [1] 0 0
2022/PID01942
Universal Trial Number (UTN)
Trial acronym
BLAST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tuberculosis, Pulmonary 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cephalexin
Treatment: Drugs - Amoxicillin-Clavulanate 500 Mg-125 Mg Oral Tablet
Other interventions - Standard of care treatment of tuberculosis

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

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


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

Treatment: Drugs: Amoxicillin-Clavulanate 500 Mg-125 Mg Oral Tablet
Participants in the intervention group will receive a combination of cephalexin and amoxicillin-clavulanate for the first 2 weeks of TB treatment

Other interventions: Standard of care treatment of tuberculosis
The control group will be given standard of care treatment of tuberculosis consisting of rifampicin, isoniazid, pyrazinamide and ethambutol
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to positivity (TTP)
Timepoint [1] 0 0
2 weeks
Secondary outcome [1] 0 0
Adverse events
Timepoint [1] 0 0
2 weeks
Secondary outcome [2] 0 0
Area under the concentration versus time curve (AUC) of cephalexin
Timepoint [2] 0 0
2 weeks
Secondary outcome [3] 0 0
Cmax of cephalexin
Timepoint [3] 0 0
2 weeks

Eligibility
Key inclusion criteria
* Consenting adults (=18 years)
* =40 kg
* Smear-positive patients with active tuberculosis, confirmed by sputum smear, TB PCR and/or GeneXpert.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/03/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2024
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Blacktown Hospital - Sydney
Recruitment hospital [2] 0 0
Royal Prince Alfred Hospital - Sydney
Recruitment hospital [3] 0 0
Western Sydney Health District - Sydney
Recruitment postcode(s) [1] 0 0
- Sydney

Funding & Sponsors
Primary sponsor type
Other
Name
Western Sydney Local Health District
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Centre Of Research Excellence in Tuberculosis Control
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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. 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).
Trial website
https://clinicaltrials.gov/study/NCT05664568
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jan-Willem Alffenaar, Professor
Address 0 0
WSLHD, Department of Pharmacy, Westmead hospital, NSW, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Jan-Willem Alffenaar, Professor
Address 0 0
Country 0 0
Phone 0 0
+61 (0)286270019
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05664568