Urinary Tract Infections
Conditions
Keywords
Non-inferiority study, Temocillin, Carbapenem, ESBL infection, Urinary tract infection
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.
Interventions
DRUGTemocillin
Intravenous temocillin disodium 2g intravenously/8h Or Renally Adjusted Equivalent (ORAE) in 30-40 min infusion or continuous intravenous (6g/24h) .
Intravenous carbapenem (meropenem 1g intravenously/8h Or Renally Adjusted Equivalent (ORAE) or imipenem 1g intravenously/8h ORAE)
Sponsors
Fondation Hôpital Saint-Joseph
French National Network of Clinical Research in Infectious Diseases (RENARCI)
URC-CIC Paris Descartes Necker Cochin
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Length of hospital stay | 60 days after randomization | Time from randomization to hospital discharge |
| 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 |
| 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 |
| Frequency of oral antibiotic switch in both arms (temocillin vs. carbapenem) | 60 days after randomization | — |
| Mortality | 60 days after randomization | Death for any reason or for infectious events |
| Pharmacokinetic of temocillin according to kidney function | 3 days after treatment initiation | Description of the temocillin plasma concentration and its variability among patients |
| 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 |
| 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 ± blood culture grows the same microorganism isolated that in the initial culture. Re-infection: same definition but with different strain in urinary culture |
Countries
France
Outcome results
None listed