Pulmonary TuberculosisPhase 2NCT02381470
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
A Phase 2 study testing Faropenem, Amoxicillin/clavulanic acid and Cefadroxil in people with Pulmonary Tuberculosis, run by National University Hospital, Singapore at 6 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Pulmonary Tuberculosis
- What is being tested?
- Faropenem, Amoxicillin/clavulanic acid and Cefadroxil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 6 sitesin 3 countries
- Study dates
- 11 Feb 2019to 2 Oct 2019
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Patient inclusion criteria:
- 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.
Patient exclusion criteria:
- 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
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
Philippines3 sites
De La Salle Health Institute
Cavite
Tropical Disease Foundation
Makati City
Lung Center Philippines
Quezon City
Uganda2 sites
Infectious Diseases Institute
Kampala
Joint Clinical Research Centre
Kampala
About this study
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.
Read the 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.
- Conditions
- Pulmonary Tuberculosis
- Being tested
- Faropenem, Amoxicillin/clavulanic acid, Cefadroxil, Rifampicin
- Keywords
- Beta lactams, adjunctive therapy, drug-sensitive tuberculosis
- Medical subject headings
- Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FaropenemDrug
Also called Farobact 200
Faropenem 600mg
Amoxicillin/clavulanic acidDrug
Also called Augmentin, Co-amoxiclav
Amoxicillin 500mg/ clavulanic acid 125mg
CefadroxilDrug
Cefadroxil 1g
RifampicinDrug
Also called Rifampin
Rifampicin 10mg/kg
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: Drug: Rifampicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of change of time to positivity (TTP) in liquid culture from day 0 to day 2
Measured: 2 days
Secondary outcomes (3)
Rate of change of TTP in liquid culture from day 0 to day 7
Measured: 7 days
Change in CFU/ml in solid culture from Day 0 to Day 2
Measured: 2 days
Change in CFU/ml in solid culture from Day 0 to Day 7
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2015 (estimated)
- Study start11 Feb 2019
- Primary completion28 Sep 2019
- Study completion2 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary TuberculosisStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- 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
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nicholas Paton, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02381470
- Sponsor's protocol ID
- Faropenem_TB
- Status last verified
- Mar 2020
- First submitted
- 2 Mar 2015
- Last updated
- 23 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02381470
- Acronym / sponsor ID
- Faropenem_TB
- Conditions
- Pulmonary Tuberculosis
- Keywords
- Beta lactams, adjunctive therapy, drug-sensitive tuberculosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Study start
- 11 Feb 2019 (actual)
- Primary completion
- 28 Sep 2019 (actual)
- Study completion
- 2 Oct 2019 (actual)
- First posted
- 6 Mar 2015 (estimated)
- 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Faropenem | Experimental | Drug: Faropenem, Drug: Amoxicillin/clavulanic acidFaropenem 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 |
| Cefadroxil | Experimental | Drug: Amoxicillin/clavulanic acid, Drug: CefadroxilCefadroxil 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 |
| Control | Active comparator | Drug: RifampicinRifampicin 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 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| FaropenemAlso: Farobact 200Faropenem 600mg | Drug | Faropenem |
| Amoxicillin/clavulanic acidAlso: Augmentin, Co-amoxiclavAmoxicillin 500mg/ clavulanic acid 125mg | Drug | Cefadroxil, Faropenem |
| CefadroxilCefadroxil 1g | Drug | Cefadroxil |
| RifampicinAlso: RifampinRifampicin 10mg/kg | Drug | Control |
Primary outcome
Rate of change of time to positivity (TTP) in liquid culture from day 0 to day 2
Time frame: 2 days
3 secondary outcomes
Rate of change of TTP in liquid culture from day 0 to day 7
Time frame: 7 days
Change in CFU/ml in solid culture from Day 0 to Day 2
Time frame: 2 days
Change in CFU/ml in solid culture from Day 0 to Day 7
Time frame: 7 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2020.
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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.
Nicholas Paton principal investigator
National University Hospital, Singapore
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Faropenem, Amoxicillin/clavulanic acid and Cefadroxil in people with Pulmonary Tuberculosis, run by National University Hospital, Singapore at 6 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: finished, as of the sponsor's last update on 23 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Philippines, Uganda, Singapore. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of change of time to positivity (TTP) in liquid culture from day 0 to day 2 (time frame: 2 days). 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 23 Mar 2020.