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

Temocillin Versus a Carbapenem as Initial Intravenous Treatment for Extended-spectrum Beta-lactamase Related Urinary Tract Infections, a Non-inferiority Study

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.

Study Overview

• Status: Completed
• Conditions: Urinary Tract Infections
• Intervention / Treatment: Drug: Temocillin; Drug: meropenem or imipenem

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.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Brest, France, 29000
    • CHRU La Cavale Blanche
  • Grenoble, France
    • CHU de Grenoble Hospital
  • Melun, France, 77
    • Melun Hospital - CHU Sud
  • Paris, France, 75018
    • Bichat Hospital
  • Paris, France, 75014
    • APHP - Cochin hospital
  • Paris, France, 75015
    • APHP - Necker-Enfants maladies Hospital
  • Paris, France, 75020
    • Groupe Hospitalier Diaconesses Croix Saint Simon
  • Paris, France, 75020
    • Tenon Hospital
  • Paris, France
    • APHP - Beaujon Hospital
  • Paris, France
    • APHP - Georges Pompidou European Hospital
  • Paris, France
    • APHP - Saint-Antoine Hospital
  • Paris, France
    • Saint-Joseph Hospital
  • Pau, France
    • CHU de PAU
  • Poitiers, France
    • CHU De Poitiers
  • Rennes, France, 35000
    • CHU Pontchaillou
  • Martinique
    • Fort-de-france, Martinique, France
      • CHU de Martinique

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous temocillin; Intravenous temocillin 2g/intravenously/8h or renally adjusted equivalent (ORAE) in 30-40 min infusion or continuous intravenous (6g/24h)	Drug: Temocillin; Intravenous temocillin disodium 2g intravenously/8h Or Renally Adjusted Equivalent (ORAE) in 30-40 min infusion or continuous intravenous (6g/24h) .
Active Comparator: Intravenous meropenem or imipenem; Intravenous meropenem or imipenem 1g/Intravenously /8h ORAE in 15-30 min infusion. Then switch to oral therapy	Drug: meropenem or imipenem; Intravenous carbapenem (meropenem 1g intravenously/8h Or Renally Adjusted Equivalent (ORAE) or imipenem 1g intravenously/8h ORAE); Other Names: Carbapenems

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	5-7 days after end of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	3-4 days after randomization
Frequency of oral antibiotic switch in both arms (temocillin vs. carbapenem)		60 days after randomization
Length of hospital stay	Time from randomization to hospital discharge	60 days after randomization
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	60 days after randomization
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	60 days after randomization
Mortality	Death for any reason or for infectious events	60 days after randomization
Pharmacokinetic of temocillin according to kidney function	Description of the temocillin plasma concentration and its variability among patients	3 days after treatment initiation
Microbiota impact study	Study treatment impact in the gut colonization with multidrug Gram negative bacilli) and temocillin resistant Gram negative bacilli	Time Frame : 5-7 days after treatment completion

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Groupe Hospitalier Paris Saint Joseph; French National Network of Clinical Research in Infectious Diseases (RENARCI)
• Investigators: Principal Investigator: Benoit PILMIS, MD, PhD, Assistance Publique - Hôpitaux de Paris; Study Chair: Olivier LORTHOLARY, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2019
• Primary Completion (Actual): October 29, 2020
• Study Completion (Actual): December 14, 2020

Study Registration Dates

• First Submitted: May 18, 2018
• First Submitted That Met QC Criteria: May 18, 2018
• First Posted (Actual): June 1, 2018

Study Record Updates

• Last Update Posted (Actual): April 19, 2021
• Last Update Submitted That Met QC Criteria: April 16, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Urinary tract infection; Non-inferiority study; Temocillin; Carbapenem; ESBL infection
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Infections; Communicable Diseases; Urinary Tract Infections; Anti-Infective Agents; Anti-Bacterial Agents; Imipenem; Meropenem; Temocillin
• Other Study ID Numbers: P 160910J; 2017-001257-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No