Tuberculosis, PulmonaryPhase 2BLASTNCT05664568
The BLAST- 1 Trial - Cephalexin+Amoxicillin-clavulanate for Tuberculosis
A Phase 2 study testing Cephalexin and Amoxicillin-Clavulanate 500 Mg-125 Mg Oral Tablet in people with Tuberculosis, Pulmonary, run by Western Sydney Local Health District at 3 sites in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis, Pulmonary
- What is being tested?
- Cephalexin and Amoxicillin-Clavulanate 500 Mg-125 Mg Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 3 sitesAustralia
- Study dates
- 15 Mar 2023to Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Consenting adults (≥18 years)
- ≥40 kg
- Smear-positive patients with active tuberculosis, confirmed by sputum smear, TB PCR and/or GeneXpert.
Who cannot join
- 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)
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- 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)
Trial locations and contacts
3 sites in 1 country.
Lina Davies Forsman, MD, PhD contact
Australia3 sites, 3 recruiting
- Not yet recruiting
Blacktown Hospital
Sydney
Tasnim Hasan, MD
- Not yet recruiting
Royal Prince Alfred Hospital
Sydney
Gregory Fox, Professor
- Recruiting
Western Sydney Health District
Sydney
Jin-Gun Cho, MD, PhD
About this study
Official title: Early Bactericidal Activity of Cephalexin and Amoxicillin-clavulanate for Susceptible Tuberculosis - BLAST 1 Trial
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.
Read more
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:
- 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:
- To asses safety and tolerability of cephalexin together with amoxicillin-clavulanate.
- 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).
Read the detailed description
Given the need for alternative and well-tolerated tuberculosis (TB) treatment options, there is scope to re-assess the potential value of already approved drugs that are known to be safe, cheap and widely available. Cephalexin, in combination with amoxicillin-clavulanate, have shown high in vitro efficacy against the TB bacteria. Both cephalexin and amoxicillin-clavulanate are Therapeutic Goods Administration (TGA) approved and are widely used in Australia for common infections.
In order to compare the bacterial killing effect of cephalexin, in combination with amoxicillin-clavulanate, with current standard of care TB treatment, we will perform an open-label randomized controlled trial.
Eligible and consenting study participants with bacteriologically confirmed sputum-smear positive pulmonary TB will be randomised to an intervention or control arm in a 1:1 ratio (15 patients in each arm) for the two weeks duration of the trial.
- Intervention arm: cephalexin 1g thrice daily + amoxicillin-clavulanate 500/125 mg thrice daily.
- Control arm: standard of care treatment for TB (rifampicin, isoniazid, ethambutol and pyrazinamide) The primary outcome is the fall in bacterial load measured by 'time to positive culture' using the BACTEC MGIT system with automated detection. Multiple sputum samples (10 in total) will be collected during the first 2 weeks of TB treatment. Six saliva samples will be collected after 4 days of treatment, in order to estimate the drug concentrations of cephalexin in the body (intervention arm only).
For a small subset of patients receiving cephalexin (n=5), a more intensive simultaneous blood and saliva sampling will be done in order to calculate the saliva:plasma ratio, in order to facilitate the estimation of plasma drug concentrations from saliva samples.
- Conditions
- Tuberculosis, Pulmonary
- Being tested
- Cephalexin, Amoxicillin-Clavulanate 500 Mg-125 Mg Oral Tablet, Standard of care treatment of tuberculosis
- Keywords
- Randomized controlled trial, Early bactericidal activity, Smear-positive TB, Betalactam antibiotics, Cephalosporin, Time to positivity
- Medical subject headings
- Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CephalexinDrug
Also called Keflex
Participants in intervention group will receive a combination of cephalexin and amoxicillin-clavulanate for the first 2 weeks of TB treatment
Amoxicillin-Clavulanate 500 Mg-125 Mg Oral TabletDrug
Also called Augmentin
Participants in the intervention group will receive a combination of cephalexin and amoxicillin-clavulanate for the first 2 weeks of TB treatment
Standard of care treatment of tuberculosisOther
Also called HREZ
The control group will be given standard of care treatment of tuberculosis consisting of rifampicin, isoniazid, pyrazinamide and ethambutol
| Study group | Role | What they receive |
|---|---|---|
| Standard of care TB | Active comparator | Standard of care treatment for TB (rifampicin, isoniazid, ethambutol and pyrazinamide according to WHO) Receives: Other: Standard of care treatment of tuberculosis |
| Cephalexin + amoxicillin-clavulanate | Experimental | Intervention arm: cephalexin 1g thrice daily + amoxicillin-clavulanate 500/125 mg thrice daily. Receives: Drug: Cephalexin; Drug: Amoxicillin-Clavulanate 500 Mg-125 Mg Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to positivity (TTP)
Early bactericidal activity measured as fall in time to positivity (TTP)
- 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.
Measured: 2 weeks
Secondary outcomes (3)
Adverse events
Tolerability - frequency, categorization and grade of adverse events according to CTCAE (Common Terminology Criteria for Adverse Events)
Measured: 2 weeks
Area under the concentration versus time curve (AUC) of cephalexin
Estimation of the pharmacokinetic parameter area under the concentration versus time curve (AUC) of cephalexin in saliva.
Measured: 2 weeks
Cmax of cephalexin
Estimation of the pharmacokinetic parameter maximum concentration (Cmax) of cephalexin saliva.
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2022
- Study start15 Mar 2023
- Primary completionJul 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tuberculosis, PulmonaryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized-controlled early bactericidal activity trial
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Western Sydney Local Health District
- Sponsor type
- University, hospital or other
- Collaborators
- Centre Of Research Excellence in Tuberculosis Control
- Responsible party
- Principal investigator, Jan-Willem Alffenaar, Western Sydney Local Health District
- Investigators
- Jan-Willem Alffenaar, Professor, Principal investigator, WSLHD, Department of Pharmacy, Westmead hospital, NSW, Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05664568
- Sponsor's protocol ID
- 2022/PID01942
- Acronym
- BLAST
- Status last verified
- Jun 2023
- First submitted
- 2 Nov 2022
- Last updated
- 26 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Bactericidal Activity of Cephalexin and Amoxicillin-clavulanate for Susceptible Tuberculosis - BLAST 1 Trial
- ClinicalTrials.gov ID
- NCT05664568
- Acronym / sponsor ID
- BLAST / 2022/PID01942
- Conditions
- Tuberculosis, Pulmonary
- Keywords
- Randomized controlled trial, Early bactericidal activity, Smear-positive TB, Betalactam antibiotics, Cephalosporin, Time to positivity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Western Sydney Local Health DistrictUniversity, hospital or other
- Collaborators
- Centre Of Research Excellence in Tuberculosis Control
- Study start
- 15 Mar 2023 (actual)
- Primary completion
- Jul 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 23 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- To asses safety and tolerability of cephalexin together with amoxicillin-clavulanate.
- 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).
Detailed description
Given the need for alternative and well-tolerated tuberculosis (TB) treatment options, there is scope to re-assess the potential value of already approved drugs that are known to be safe, cheap and widely available. Cephalexin, in combination with amoxicillin-clavulanate, have shown high in vitro efficacy against the TB bacteria. Both cephalexin and amoxicillin-clavulanate are Therapeutic Goods Administration (TGA) approved and are widely used in Australia for common infections.
In order to compare the bacterial killing effect of cephalexin, in combination with amoxicillin-clavulanate, with current standard of care TB treatment, we will perform an open-label randomized controlled trial.
Eligible and consenting study participants with bacteriologically confirmed sputum-smear positive pulmonary TB will be randomised to an intervention or control arm in a 1:1 ratio (15 patients in each arm) for the two weeks duration of the trial.
- Intervention arm: cephalexin 1g thrice daily + amoxicillin-clavulanate 500/125 mg thrice daily.
- Control arm: standard of care treatment for TB (rifampicin, isoniazid, ethambutol and pyrazinamide) The primary outcome is the fall in bacterial load measured by 'time to positive culture' using the BACTEC MGIT system with automated detection. Multiple sputum samples (10 in total) will be collected during the first 2 weeks of TB treatment. Six saliva samples will be collected after 4 days of treatment, in order to estimate the drug concentrations of cephalexin in the body (intervention arm only).
For a small subset of patients receiving cephalexin (n=5), a more intensive simultaneous blood and saliva sampling will be done in order to calculate the saliva:plasma ratio, in order to facilitate the estimation of plasma drug concentrations from saliva samples.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized-controlled early bactericidal activity trial
| Arm | Type | Receives |
|---|---|---|
| Standard of care TB | Active comparator | Other: Standard of care treatment of tuberculosisStandard of care treatment for TB (rifampicin, isoniazid, ethambutol and pyrazinamide according to WHO) |
| Cephalexin + amoxicillin-clavulanate | Experimental | Drug: Cephalexin, Drug: Amoxicillin-Clavulanate 500 Mg-125 Mg Oral TabletIntervention arm: cephalexin 1g thrice daily + amoxicillin-clavulanate 500/125 mg thrice daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Consenting adults (≥18 years)
- ≥40 kg
- Smear-positive patients with active tuberculosis, confirmed by sputum smear, TB PCR and/or GeneXpert.
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CephalexinAlso: KeflexParticipants in intervention group will receive a combination of cephalexin and amoxicillin-clavulanate for the first 2 weeks of TB treatment | Drug | Cephalexin + amoxicillin-clavulanate |
| Amoxicillin-Clavulanate 500 Mg-125 Mg Oral TabletAlso: AugmentinParticipants in the intervention group will receive a combination of cephalexin and amoxicillin-clavulanate for the first 2 weeks of TB treatment | Drug | Cephalexin + amoxicillin-clavulanate |
| Standard of care treatment of tuberculosisAlso: HREZThe control group will be given standard of care treatment of tuberculosis consisting of rifampicin, isoniazid, pyrazinamide and ethambutol | Other | Standard of care TB |
Primary outcome
Time to positivity (TTP)
Time frame: 2 weeks
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.
3 secondary outcomes
Adverse events
Time frame: 2 weeks
Area under the concentration versus time curve (AUC) of cephalexin
Time frame: 2 weeks
Cmax of cephalexin
Time frame: 2 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lina Davies Forsman, MD, PhD contact
Jan-Willem Alffenaar, Professor principal investigator
WSLHD, Department of Pharmacy, Westmead hospital, NSW, Australia
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cephalexin and Amoxicillin-Clavulanate 500 Mg-125 Mg Oral Tablet in people with Tuberculosis, Pulmonary, run by Western Sydney Local Health District at 3 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jan-Willem Alffenaar, Professor (+61 (0)286270019, johannes.alffenaar@nsw.health.gov.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to positivity (TTP) (time frame: 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2023.