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

Urinary Tract Infections Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03543436
• Other study ID #: P 160910J
• Secondary ID: 2017-001257-14
• Status: Completed
• Phase: Phase 3
• Start date: January 4, 2019
• Est. completion date: December 14, 2020

Study information

• Verified date: April 2021
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: December 14, 2020
• Est. primary completion date: October 29, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Infection
• Urinary Tract Infections

Intervention

Drug:
• Temocillin
Intravenous temocillin disodium 2g intravenously/8h Or Renally Adjusted Equivalent (ORAE) in 30-40 min infusion or continuous intravenous (6g/24h) .
• meropenem or imipenem
Intravenous carbapenem (meropenem 1g intravenously/8h Or Renally Adjusted Equivalent (ORAE) or imipenem 1g intravenously/8h ORAE)

Locations

Country	Name	City	State
France	CHRU La Cavale Blanche	Brest
France	CHU de Martinique	Fort-de-france	Martinique
France	CHU de Grenoble Hospital	Grenoble
France	Melun Hospital - CHU Sud	Melun
France	APHP - Beaujon Hospital	Paris
France	APHP - Cochin Hospital	Paris
France	APHP - Georges Pompidou European Hospital	Paris
France	APHP - Necker-Enfants maladies Hospital	Paris
France	APHP - Saint-Antoine Hospital	Paris
France	Bichat hospital	Paris
France	Groupe Hospitalier Diaconesses Croix Saint Simon	Paris
France	Saint-Joseph Hospital	Paris
France	Tenon Hospital	Paris
France	CHU de Pau	Pau
France	CHU de Poitiers	Poitiers
France	CHU Pontchaillou	Rennes

Sponsors (3)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	French National Network of Clinical Research in Infectious Diseases (RENARCI), Groupe Hospitalier Paris Saint Joseph

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Frequency of oral antibiotic switch in both arms (temocillin vs. carbapenem)		60 days after randomization
Secondary	Length of hospital stay	Time from randomization to hospital discharge	60 days after randomization
Secondary	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
Secondary	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
Secondary	Mortality	Death for any reason or for infectious events	60 days after randomization
Secondary	Pharmacokinetic of temocillin according to kidney function	Description of the temocillin plasma concentration and its variability among patients	3 days after treatment initiation
Secondary	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