Evaluation of the Non-inferiority of Cefoxitin Versus Imipenem/Cilastatin in the Treatment of Urinary Tract Infections Caused by ESBL-producing Escherichia Coli

NCT02474706 | Terminated Phase 4 DMC

• 1 other identifier: PHRC N 2013/COLIFOX-MAY/SR
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Background Information: Infections caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are becoming increasingly common owing to incorrect use of antibiotics and cross-transmission in healthcare establishments. These give rise to major problems in standard clinical practice: penicillins and cephalosporins cannot be used, and resistance to the other classes of antibiotics normally used, such as fluoroquinolones or cotrimoxazole, is very frequently observed. The current therapeutic strategy involves the use of a carbapenem, which represents the last effective solution on an individual level. However, the growing use thereof is contributing, collectively, to the development of resistance due to the production of carbapenemases, which will become a major public health problem, with a potential therapeutic dead-end. This observation is particularly worrying due to the very small number of antibiotic agents currently in development. Infectious disease specialists and microbiologists are thus examining alternative agents to carbapenems in the management of infections caused by ESBL-producing E. coli. One of the avenues which could be developed is the use of known agents, already on the market, which are active in vitro on ESBL-producing E. coli, but which are not currently recommended for this indication in standard practice due to the lack of conclusive studies. Cefoxitin, an antibiotic belonging to the cephamycin group, could thus represent an alternative of particular interest in the treatment of infections caused by ESBL-producing E. coli, and help limit the use of carbapenems. The implementation of a prospective, randomized, non-inferiority study on ertapenem and cefoxitin is of the most interest from a methodological perspective. It will enable recommendations to be drawn up, with a high level of evidence, very long-awaited in the field. Primary objective: To evaluate the bacteriological non-inferiority of cefoxitin versus imipenem in the treatment of non-severe urinary tract infections (other than cystitis) caused by ESBL-producing E. coli susceptible in vitro to cefoxitin. Secondary objectives:

• To evaluate the clinical non-inferiority of cefoxitin versus imipenem in the treatment of non-severe urinary tract infections (other than cystitis) caused by ESBL-producing E. coli susceptible in vitro to cefoxitin.
• To evaluate the impact of cefoxitin and imipenem on the emergence of multiresistant bacteria in the gut flora.

Conditions

Urinary Tract Infections

Keywords

cefoxitin Patient safety; Infectious diseases; Extended-Spectrum β-lactamases E.coli; Antibiotics

Outcome Measures

Primary Outcomes (1)

• Control urine culture negative

  7 days after the end of treatment

Secondary Outcomes (3)

• absence of fever

  3 days after the beginning of study treatment

• presence of multiresistant bacteria in a rectal swab

  7 days after the end of treatment

• Composite outcome measure consisting of resolution of clinical signs observed on diagnosis

  7 days after the end of treatment

Study Arms (2)

cefoxitin

EXPERIMENTAL

Cefoxitin 2 g administered intravenously three times a day. during 10 days for the treatment of pyelonephritis during 21 days for the treatment of prostatitis

Drug: Cefoxitin

imipenem

ACTIVE COMPARATOR

Imimpenem 1 g administered intravenously three times a day. during 10 days for the treatment of pyelonephritis during 21 days for the treatment of prostatitis

Drug: imipenem

Interventions

Cefoxitin DRUG

cefoxitin

imipenem DRUG

imipenem

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Patient admitted to any medical or surgical department in the participating centre
• Documented urinary tract infection (other than cystitis), with or without bacteremia, caused by ESBL-producing E. coli susceptible in vitro to cefoxitin (minimal inhibition concentration \<= 8 mg/L and /or diameter ≥ 19 mm according to CA-SFM 2015) and resistant to fluoroquinolones and to association trimethoprim-sulfamethoxazole. An E. Coli urinary tract infection is defined according to SPILF 2014 Clarification by a leucocytury ≥ 104/mL and clinical significant limit at 103 UFC/ml, for the men or the women.
• Informed consent signed by the patient
• Patient affiliated to a French Sécurité Social regimen

You may not qualify if:

• Serious infection (severe sepsis, septic shock)
• Pregnant or breast-feeding women
• Chronic kidney failure (creatinine clearance \< 30 ml/min) and/or dialysis
• Hypersensibility to imipenem/cilastatine, to cefoxitine
• Hypersensibility to another antibiotics of cephalosporine class
• Hypersensibility to another antibiotics of carbapenem class
• Severe hypersensibility (ex :anaphylactic reaction, or serious cutaneous reaction) to all other antibiotics from beta lactamines family (ex : penicillins, monobactam)
• Treatment with ganciclovir and/or valproic acid
• Infection on the urinary cathether
• Empirical antibiotic therapy including an aminoglycoside
• Patient being treated with antibiotic(s) for another infection
• Patient participating to another interventional study
• Patient not compliant according to the investigator's opinion
• Patient under guardianship

Sponsors & Collaborators

• Central Hospital, Nancy, France: lead

Study Sites (1)

CHRU Nancy

Nancy, 54511, France

Location

MeSH Terms

Conditions

Urinary Tract Infections; Communicable Diseases

Interventions

Cefoxitin; Imipenem

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cephamycins; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thienamycins; Carbapenems

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2015
• First Posted: June 18, 2015
• Study Start: March 1, 2016
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: August 11, 2017

Record last verified: 2017-08

Locations

FR (1)