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Trial record 10 of 170 for:    "Pulmonary Tuberculosis"

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

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ClinicalTrials.gov Identifier: NCT02381470
Recruitment Status : Not yet recruiting
First Posted : March 6, 2015
Last Update Posted : December 18, 2018
Sponsor:
Information provided by (Responsible Party):
National University Hospital, Singapore

Tracking Information
First Submitted Date  ICMJE March 2, 2015
First Posted Date  ICMJE March 6, 2015
Last Update Posted Date December 18, 2018
Estimated Study Start Date  ICMJE December 2018
Estimated Primary Completion Date March 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 16, 2018)
Rate of change of time to positivity (TTP) in liquid culture from day 0 to day 2 [ Time Frame: 2 days ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 5, 2015)
Rate of change of time to positivity (TTP) in liquid culture from day 0 to day 5 [ Time Frame: 5 days ]
Change History Complete list of historical versions of study NCT02381470 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 16, 2018)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 5, 2015)
  • Rate of change of TTP in liquid culture from day 0 to day 2 [ Time Frame: 2 days ]
  • Change in CFU/ml in solid culture from Day 0 to Day 5 [ Time Frame: 5 days ]
  • Change in CFU/ml in solid culture from Day 0 to Day 2 [ Time Frame: 2 days ]
  • Cumulative bactericidal activity (WBA) at Day 2 [ Time Frame: 2 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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.
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 45 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Pulmonary Tuberculosis
Intervention  ICMJE
  • Drug: Faropenem
    Faropenem 600mg
    Other Name: Farobact 200
  • Drug: Amoxicillin/clavulanic acid
    Amoxicillin 500mg/ clavulanic acid 125mg
    Other Names:
    • Augmentin
    • Co-amoxiclav
  • Drug: Cefadroxil
    Cefadroxil 1g
  • Drug: Rifampicin
    Rifampicin 10mg/kg
    Other Name: Rifampin
Study Arms  ICMJE
  • Experimental: Faropenem
    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
    Interventions:
    • Drug: Faropenem
    • Drug: Amoxicillin/clavulanic acid
  • Experimental: Cefadroxil
    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
    Interventions:
    • Drug: Amoxicillin/clavulanic acid
    • Drug: Cefadroxil
  • Active Comparator: Control
    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
    Intervention: Drug: Rifampicin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: December 16, 2018)
45
Original Estimated Enrollment  ICMJE
 (submitted: March 5, 2015)
28
Estimated Study Completion Date  ICMJE April 2019
Estimated Primary Completion Date March 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Patient inclusion criteria:

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

Patient exclusion criteria:

  1. Suspected miliary TB or TB meningitis
  2. Patients receiving any TB treatment within the previous 6 months
  3. Patients too ill to tolerate a 2-3 day delay in standard therapy
  4. Concurrent bacterial pneumonia
  5. Known hypersensitivity to beta-lactam drugs (penicillins, carbapenems) or rifampicin
  6. History of severe allergies or severe asthma
  7. Receiving loop diuretics
  8. Estimated creatinine clearance < 80 ml/min on screening blood test
  9. ALT > 2.5 times upper limit of normal on screening blood test.
  10. Presence of rifampicin resistance on GeneXpert (or alternative molecular test).
  11. Women who are currently pregnant or breastfeeding.
  12. Any other significant condition that would, in the opinion of the investigator, compromise the patient's safety or outcome in the trial.
  13. Participation in other clinical intervention trial or research protocol
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Claire Naftalin +65 6601 5373 claire_naftalin@nuhs.edu.sg
Contact: Jing Wang +65 6601 5374 mdcwaj@nus.edu.sg
Listed Location Countries  ICMJE Philippines,   Singapore
Removed Location Countries Malaysia
 
Administrative Information
NCT Number  ICMJE NCT02381470
Other Study ID Numbers  ICMJE Faropenem_TB
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National University Hospital, Singapore
Study Sponsor  ICMJE National University Hospital, Singapore
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Nicholas Paton National University Hospital, Singapore
PRS Account National University Hospital, Singapore
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP