NCT02142751

Fosfomycin Versus Meropenem or Ceftriaxone in Bacteriemic Infections Caused by Multidrug Resistance in E.Coli

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

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 161 (actual)
• Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Infection Due to ESBL Escherichia Coli

Interventions

Type	Name	Description
DRUG	Fosfomycin sodium intravenous	4g every 6 hours iv (60 min infusion)
DRUG	Meropenem intravenous	1g every 8 hours (15-30 min infusion) It depends on strain sensitivity: Strain with resistance to cephalosporins
DRUG	Ceftriaxone intravenous	1g every 24 hours iv (2-4 min infusion) It depends on strain sensitivity: Strain with resistance to quinolone but sensitivity to cephalosporins

Timeline

• Start date: 2014-07-01
• Primary completion: 2018-12-01
• Completion: 2019-03-01
• First posted: 2014-05-20
• Last updated: 2019-08-06

Locations

22 sites across 1 country: Spain