Temocillin Versus a Carbapenem as Initial Intravenous Treatment for ESBL Related Urinary Tract Infections
- Conditions
- Urinary Tract Infections
- Interventions
- Registration Number
- NCT03543436
- Lead Sponsor
- Assistance Publique - HΓ΄pitaux de Paris
- 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-Ξ±-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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 29
- Adult (β₯ 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Intravenous meropenem or imipenem meropenem or imipenem Intravenous meropenem or imipenem 1g/Intravenously /8h ORAE in 15-30 min infusion. Then switch to oral therapy Intravenous temocillin Temocillin Intravenous temocillin 2g/intravenously/8h or renally adjusted equivalent (ORAE) in 30-40 min infusion or continuous intravenous (6g/24h)
- Primary Outcome Measures
Name Time Method Clinical and microbiological cure 5-7 days after end of treatment 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
Name Time Method Clinical recurrences 60 days after randomization 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 Β± blood culture grows the same microorganism isolated that in the initial culture.
Re-infection: same definition but with different strain in urinary cultureMortality 60 days after randomization Death for any reason or for infectious events
Frequency of oral antibiotic switch in both arms (temocillin vs. carbapenem) 60 days after randomization Length of hospital stay 60 days after randomization Time from randomization to hospital discharge
Persistent cure rate 60 days after randomization 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
Microbiota impact study Time Frame : 5-7 days after treatment completion Study treatment impact in the gut colonization with multidrug Gram negative bacilli) and temocillin resistant Gram negative bacilli
Early microbiological eradication 3-4 days after randomization 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
Pharmacokinetic of temocillin according to kidney function 3 days after treatment initiation Description of the temocillin plasma concentration and its variability among patients
Trial Locations
- Locations (16)
APHP - Saint-Antoine Hospital
π«π·Paris, France
CHU de Grenoble Hospital
π«π·Grenoble, France
Bichat hospital
π«π·Paris, France
APHP - Georges Pompidou European Hospital
π«π·Paris, France
CHU Pontchaillou
π«π·Rennes, France
CHU de Martinique
π«π·Fort-de-france, Martinique, France
CHRU La Cavale Blanche
π«π·Brest, France
Melun Hospital - CHU Sud
π«π·Melun, France
APHP - Necker-Enfants maladies Hospital
π«π·Paris, France
APHP - Cochin Hospital
π«π·Paris, France
Groupe Hospitalier Diaconesses Croix Saint Simon
π«π·Paris, France
APHP - Beaujon Hospital
π«π·Paris, France
Tenon Hospital
π«π·Paris, France
Saint-Joseph Hospital
π«π·Paris, France
CHU de Pau
π«π·Pau, France
CHU de Poitiers
π«π·Poitiers, France