Infection Due to ESBL Escherichia Coli Clinical Trial
Official title:
Phase 3, Randomized, Controlled Multicentric, Open-label Clinical Trial to Prove Non-Inferiority of Fosfomycin vs Meropenem or Ceftriaxone in the Treatment of Bacteriemic Urinary Infection Due to Multidrug Resistance in E.Coli
Enterobacterieaceae (and specially Escherichia coli) showing resistance due to
multidrug-resistant Escherichia coli, plasmid mediated AmpC or quinolone resistance caused by
chromosomal mechanisms have spread worldwide during the last decades. This is important
because many of these isolates are also resistant to other first-line agents such as
fluoroquinolones or aminoglycosides, leaving few available options for therapy, and this
condition is associated with increased morbidity- mortality and length of hospital stay.
While carbapenems are considered the drugs of choice for multidrug-resistant Escherichia coli
and AmpC producers, recent data suggests that certain alternatives may be suitable for some
types of infections.
At the present time, finding therapeutic alternatives to carbapenems and cephalosporins for
the treatment of invasive infections due to multidrug-resistant Escherichia coli is critical.
Fosfomycin was discovered more than 40 years ago but was not investigated according to
present standards, and thus is not used in clinical practice except in desperate situations.
It is one of the so-considered neglected antibiotics with high potential interest for the
future.
With the aim of demonstrate the clinical non-inferiority of intravenous fosfomycin compared
to meropenem or ceftriaxone in the treatment of bacteraemic urinary tract infections caused
by multidrug-resistant Escherichia coli . The investigators propose a "real practise"
randomised, controlled, multicentre phase III clinical trial to compare the clinical and
microbiological efficacy and safety of intravenous fosfomycin (4 grammes every 6 hours) with
meropenem (1 gramme every 8 hours) or ceftriaxone (1 gramme every 24 hours) as targeted
therapy of the previously specified infection; change to oral therapy according to predefined
options is allowed in both arms after 5 days. Follow-up for the study is planned up to 60
days.
The FOREST study is a phase 3, randomised, controlled, multicentric, open-label clinical
trial to prove the noninferiority of fosfomycin versus meropenem in the targeted treatment of
bacteraemic UTI due to ESBL-EC, designed as a real practice trial. It is a non-commercial,
investigator-driven clinical study funded through a public competitive call by Instituto de
Salud Carlos III, Spanish Ministry of Economy (PI13/01282).
The study is coordinated by investigators from Hospital Universitario Virgen Macarena in
Seville, Spain; the sponsorship is performed by Fundación Pública Andaluza para la Gestión de
la Investigación en Salud de Sevilla (FISEVI), of which the sponsor-scientific
responsibilities are delegated to the CTU (Clinical Trial Unit—Hospital Universitario Virgen
del Rocío, Seville, Spain). All participating patients or their relatives must give written
informed consent before any study procedures occur, including the withdrawal of biological
samples for the study.
The hypothesis to test is that intravenous fosfomycin is not inferior to meropenem for the
targeted treatment of bacteraemic UTI caused by ESBL-EC in terms of efficacy.
The primary objective of the study is to demonstrate that intravenous fosfomycin is not
inferior to meropenem for reaching clinical and microbiological cure 5-7 days after the
completion of treatment.
Secondary objectives include comparing the early clinical and microbiological response,
30-day mortality, hospital stay, recurrence rate, safety and impact on intestinal
colonisation by MDR Gram-negative bacilli, evaluation of the rate of resistance development
to fosfomycin and blood level concentration of fosfomycin.
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| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Enrolling by invitation |
NCT02456818 -
Assessing the Effect of Contact Isolation on Nosocomial Colonization With ESBL-EC in German Hematology/Oncology Wards
|
N/A |