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Temocillin Versus a Carbapenem as Initial Intravenous Treatment for ESBL Related Urinary Tract Infections (TEMO-CARB)

Primary Purpose

Urinary Tract Infections

Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Temocillin
meropenem or imipenem
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Urinary Tract Infections focused on measuring Non-inferiority study, Temocillin, Carbapenem, ESBL infection, Urinary tract infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Adult (≥ 18 years)
  • Hospitalized patient with clinically significant monomicrobial UTI
  • Complicated UTI due to ESBL producing enterobacteriaceae (pyelonephritis, prostatitis or renal abscess) requiring parenteral antimicrobial therapy
  • Susceptibility to temocillin and carbapenem as evidenced by testing results
  • For woman able to procreate: negative pregnancy test and use of an effective method of contraception (abstinence, oral contraceptives, intra-uterine device, diaphragm with spermicide and condom). All forms of hormonal contraception are acceptable
  • Signed informed consent by patient himself (able or under curatorship) or his legal representative (patient unable to give his consent or under tutorship)
  • Patient affiliated to the social security system

Exclusion Criteria:

  • Patient infected with a bacteria which is not an ESBL-producing enterobacteriaceae.
  • Polymicrobial infection.
  • Hypersensitivity and/or previous intolerance to carbapenem or temocillin, or penicillins or any other beta-lactam.
  • Patient with a contraindication to any of the drugs to be used in research
  • Patient presenting another site of infection than urinary (except onset of bacteraemia from urinary tract origin due to Gram negative bacteria).
  • Woman who is pregnant, breastfeeding, or expecting to conceive at any time during the study (pregnancy test will be conducted for woman without menopause).
  • Palliative care of life expectancy < 90 days.
  • Ongoing empirical treatment of the urinary tract infections with carbapenem or temocillin > 24 hours before randomization
  • Delay in randomization > 48 hours after identification of ESBL producing enterobacteriaceae in urinary and/or blood culture.
  • Participation in other clinical trial for the infection.

Sites / Locations

  • CHU de Martinique
  • CHRU La Cavale Blanche
  • CHU de Grenoble Hospital
  • Melun Hospital - CHU Sud
  • APHP - Cochin Hospital
  • APHP - Necker-Enfants maladies Hospital
  • Bichat hospital
  • Groupe Hospitalier Diaconesses Croix Saint Simon
  • Tenon Hospital
  • APHP - Beaujon Hospital
  • APHP - Georges Pompidou European Hospital
  • APHP - Saint-Antoine Hospital
  • Saint-Joseph Hospital
  • CHU de Pau
  • CHU de Poitiers
  • CHU Pontchaillou

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Intravenous temocillin

Intravenous meropenem or imipenem

Arm Description

Intravenous temocillin 2g/intravenously/8h or renally adjusted equivalent (ORAE) in 30-40 min infusion or continuous intravenous (6g/24h)

Intravenous meropenem or imipenem 1g/Intravenously /8h ORAE in 15-30 min infusion. Then switch to oral therapy

Outcomes

Primary Outcome Measures

Clinical and microbiological cure
The primary endpoint, was defined as achieving both clinical cure and microbiological eradication of all baseline pathogens 5-7 days after completion of treatment. Clinical cure is defined as complete resolution, substantial improvement or return to pre-infections signs and symptoms of complicated lower urinary tract infections or pyelonephritis without the need for additional antibiotic therapy Microbiological efficacy will be assessed by quantitative urine culture and defined as follows < 10^3 Colony Forming Unit (CFU)/mL of the baseline pathogens

Secondary Outcome Measures

Early microbiological eradication
Microbiological eradication will be assessed by quantitative urine culture and defined as follows < 10^3 colony forming unit Colony Forming Unit (CFU)/mL of the baseline pathogens
Frequency of oral antibiotic switch in both arms (temocillin vs. carbapenem)
Length of hospital stay
Time from randomization to hospital discharge
Persistent cure rate
Clinical cure is defined as complete resolution, substantial improvement or return to pre-infections signs and symptoms of complicated lower urinary tract infections or pyelonephritis without the need for additional antibiotic therapy
Clinical recurrences
Relapse: new symptoms of urinary tract infection in a patient previously considered as clinically or microbiologically cured in the visit 5-7 days after treatment completion plus positive urine ± blood culture grows the same microorganism isolated that in the initial culture. Re-infection: same definition but with different strain in urinary culture
Mortality
Death for any reason or for infectious events
Pharmacokinetic of temocillin according to kidney function
Description of the temocillin plasma concentration and its variability among patients
Microbiota impact study
Study treatment impact in the gut colonization with multidrug Gram negative bacilli) and temocillin resistant Gram negative bacilli

Full Information

First Posted
May 18, 2018
Last Updated
April 16, 2021
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Fondation Hôpital Saint-Joseph, French National Network of Clinical Research in Infectious Diseases (RENARCI)
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1. Study Identification

Unique Protocol Identification Number
NCT03543436
Brief Title
Temocillin Versus a Carbapenem as Initial Intravenous Treatment for ESBL Related Urinary Tract Infections
Acronym
TEMO-CARB
Official Title
Temocillin Versus a Carbapenem as Initial Intravenous Treatment for Extended-spectrum Beta-lactamase Related Urinary Tract Infections, a Non-inferiority Study
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
January 4, 2019 (Actual)
Primary Completion Date
October 29, 2020 (Actual)
Study Completion Date
December 14, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Fondation Hôpital Saint-Joseph, French National Network of Clinical Research in Infectious Diseases (RENARCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
TEMO-CARB is a phase 3, randomized, controlled, multicentre, open-label pragmatic clinical trial to test the non-inferiority of temocillin versus carbapenem as initial intravenous treatment of Urinary Tract Infection (UTI) due to extended-spectrum beta-lactamase (ESBL) producing enterobacteriaceae.
Detailed Description
Urinary tract infections are among the most common bacterial infections that are treated in the community by an empirical antibiotic treatment regimen. Enterobacteriaceae are the most common bacteria involved in urinary tract infection. Since 2006, extended-spectrum beta-lactamase (ESBL) producing enterobacteriaceae have spread in France, as elsewhere. Finding therapeutic alternatives to carbapenems in infections caused by ESBL producing enterobacteriaceae is imperative. Although temocillin, 6-α-methoxy derivative of ticarcillin has been suggested as a potential alternative to carbapenem therapy for ESBL related infections, it was not investigated in accordance with current standard. The hypothesis to test in this study is that temocillin is not inferior to a carbapenem as initial intravenous treatment of urinary tract infections caused by ESBL producing enterobacteriaceae.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urinary Tract Infections
Keywords
Non-inferiority study, Temocillin, Carbapenem, ESBL infection, Urinary tract infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intravenous temocillin
Arm Type
Experimental
Arm Description
Intravenous temocillin 2g/intravenously/8h or renally adjusted equivalent (ORAE) in 30-40 min infusion or continuous intravenous (6g/24h)
Arm Title
Intravenous meropenem or imipenem
Arm Type
Active Comparator
Arm Description
Intravenous meropenem or imipenem 1g/Intravenously /8h ORAE in 15-30 min infusion. Then switch to oral therapy
Intervention Type
Drug
Intervention Name(s)
Temocillin
Intervention Description
Intravenous temocillin disodium 2g intravenously/8h Or Renally Adjusted Equivalent (ORAE) in 30-40 min infusion or continuous intravenous (6g/24h) .
Intervention Type
Drug
Intervention Name(s)
meropenem or imipenem
Other Intervention Name(s)
Carbapenems
Intervention Description
Intravenous carbapenem (meropenem 1g intravenously/8h Or Renally Adjusted Equivalent (ORAE) or imipenem 1g intravenously/8h ORAE)
Primary Outcome Measure Information:
Title
Clinical and microbiological cure
Description
The primary endpoint, was defined as achieving both clinical cure and microbiological eradication of all baseline pathogens 5-7 days after completion of treatment. Clinical cure is defined as complete resolution, substantial improvement or return to pre-infections signs and symptoms of complicated lower urinary tract infections or pyelonephritis without the need for additional antibiotic therapy Microbiological efficacy will be assessed by quantitative urine culture and defined as follows < 10^3 Colony Forming Unit (CFU)/mL of the baseline pathogens
Time Frame
5-7 days after end of treatment
Secondary Outcome Measure Information:
Title
Early microbiological eradication
Description
Microbiological eradication will be assessed by quantitative urine culture and defined as follows < 10^3 colony forming unit Colony Forming Unit (CFU)/mL of the baseline pathogens
Time Frame
3-4 days after randomization
Title
Frequency of oral antibiotic switch in both arms (temocillin vs. carbapenem)
Time Frame
60 days after randomization
Title
Length of hospital stay
Description
Time from randomization to hospital discharge
Time Frame
60 days after randomization
Title
Persistent cure rate
Description
Clinical cure is defined as complete resolution, substantial improvement or return to pre-infections signs and symptoms of complicated lower urinary tract infections or pyelonephritis without the need for additional antibiotic therapy
Time Frame
60 days after randomization
Title
Clinical recurrences
Description
Relapse: new symptoms of urinary tract infection in a patient previously considered as clinically or microbiologically cured in the visit 5-7 days after treatment completion plus positive urine ± blood culture grows the same microorganism isolated that in the initial culture. Re-infection: same definition but with different strain in urinary culture
Time Frame
60 days after randomization
Title
Mortality
Description
Death for any reason or for infectious events
Time Frame
60 days after randomization
Title
Pharmacokinetic of temocillin according to kidney function
Description
Description of the temocillin plasma concentration and its variability among patients
Time Frame
3 days after treatment initiation
Title
Microbiota impact study
Description
Study treatment impact in the gut colonization with multidrug Gram negative bacilli) and temocillin resistant Gram negative bacilli
Time Frame
Time Frame : 5-7 days after treatment completion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adult (≥ 18 years) Hospitalized patient with clinically significant monomicrobial UTI Complicated UTI due to ESBL producing enterobacteriaceae (pyelonephritis, prostatitis or renal abscess) requiring parenteral antimicrobial therapy Susceptibility to temocillin and carbapenem as evidenced by testing results For woman able to procreate: negative pregnancy test and use of an effective method of contraception (abstinence, oral contraceptives, intra-uterine device, diaphragm with spermicide and condom). All forms of hormonal contraception are acceptable Signed informed consent by patient himself (able or under curatorship) or his legal representative (patient unable to give his consent or under tutorship) Patient affiliated to the social security system Exclusion Criteria: Patient infected with a bacteria which is not an ESBL-producing enterobacteriaceae. Polymicrobial infection. Hypersensitivity and/or previous intolerance to carbapenem or temocillin, or penicillins or any other beta-lactam. Patient with a contraindication to any of the drugs to be used in research Patient presenting another site of infection than urinary (except onset of bacteraemia from urinary tract origin due to Gram negative bacteria). Woman who is pregnant, breastfeeding, or expecting to conceive at any time during the study (pregnancy test will be conducted for woman without menopause). Palliative care of life expectancy < 90 days. Ongoing empirical treatment of the urinary tract infections with carbapenem or temocillin > 24 hours before randomization Delay in randomization > 48 hours after identification of ESBL producing enterobacteriaceae in urinary and/or blood culture. Participation in other clinical trial for the infection.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benoit PILMIS, MD, PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Olivier LORTHOLARY, MD, PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Study Chair
Facility Information:
Facility Name
CHU de Martinique
City
Fort-de-france
State/Province
Martinique
Country
France
Facility Name
CHRU La Cavale Blanche
City
Brest
ZIP/Postal Code
29000
Country
France
Facility Name
CHU de Grenoble Hospital
City
Grenoble
Country
France
Facility Name
Melun Hospital - CHU Sud
City
Melun
ZIP/Postal Code
77
Country
France
Facility Name
APHP - Cochin Hospital
City
Paris
ZIP/Postal Code
75014
Country
France
Facility Name
APHP - Necker-Enfants maladies Hospital
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Bichat hospital
City
Paris
ZIP/Postal Code
75018
Country
France
Facility Name
Groupe Hospitalier Diaconesses Croix Saint Simon
City
Paris
ZIP/Postal Code
75020
Country
France
Facility Name
Tenon Hospital
City
Paris
ZIP/Postal Code
75020
Country
France
Facility Name
APHP - Beaujon Hospital
City
Paris
Country
France
Facility Name
APHP - Georges Pompidou European Hospital
City
Paris
Country
France
Facility Name
APHP - Saint-Antoine Hospital
City
Paris
Country
France
Facility Name
Saint-Joseph Hospital
City
Paris
Country
France
Facility Name
CHU de Pau
City
Pau
Country
France
Facility Name
CHU de Poitiers
City
Poitiers
Country
France
Facility Name
CHU Pontchaillou
City
Rennes
ZIP/Postal Code
35000
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

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Temocillin Versus a Carbapenem as Initial Intravenous Treatment for ESBL Related Urinary Tract Infections

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