Clinical trial NCT03543436: Temocillin Versus a Carbapenem as Initial Intravenous Treatment for ESBL Related Urinary Tract Infections
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Urinary Tract Infections
Keywords: Non-inferiority study
Temocillin
Carbapenem
ESBL infection
Urinary tract infection
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Fondation Hôpital Saint-Joseph
name: French National Network of Clinical Research in Infectious Diseases (RENARCI)
First posted: 2018-06-01
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Clinical and microbiological cure
timeFrame: 5-7 days after end of treatment
Secondary outcomes:
measure: Early microbiological eradication
timeFrame: 3-4 days after randomization
measure: Frequency of oral antibiotic switch in both arms (temocillin vs. carbapenem)
timeFrame: 60 days after randomization
measure: Length of hospital stay
timeFrame: 60 days after randomization
measure: Persistent cure rate
timeFrame: 60 days after randomization
measure: Clinical recurrences
timeFrame: 60 days after randomization
measure: Mortality
timeFrame: 60 days after randomization
measure: Pharmacokinetic of temocillin according to kidney function
timeFrame: 3 days after treatment initiation
measure: Microbiota impact study
timeFrame: Time Frame : 5-7 days after treatment completion
Other outcomes:
Locations:
city: Fort-de-france
country: France
facility: CHU de Martinique
state: Martinique
city: Brest
country: France
facility: CHRU La Cavale Blanche
city: Grenoble
country: France
facility: CHU de Grenoble Hospital
city: Melun
country: France
facility: Melun Hospital - CHU Sud
city: Paris
country: France
facility: APHP - Cochin Hospital
city: Paris
country: France
facility: APHP - Necker-Enfants maladies Hospital
city: Paris
country: France
facility: Bichat hospital
city: Paris
country: France
facility: Groupe Hospitalier Diaconesses Croix Saint Simon
city: Paris
country: France
facility: Tenon Hospital
city: Paris
country: France
facility: APHP - Beaujon Hospital
city: Paris
country: France
facility: APHP - Georges Pompidou European Hospital
city: Paris
country: France
facility: APHP - Saint-Antoine Hospital
city: Paris
country: France
facility: Saint-Joseph Hospital
city: Pau
country: France
facility: CHU de Pau
city: Poitiers
country: France
facility: CHU de Poitiers
city: Rennes
country: France
facility: CHU Pontchaillou
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Benoit PILMIS, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Assistance Publique - Hôpitaux de Paris
name: Olivier LORTHOLARY, MD, PhD
role: STUDY_CHAIR
References: