Clinical trial NCT04076436: Efficacy of Intravenous Fosfomycin in the Treatment of Complicated Urinary in Real-life Conditions.
Official title: Efficacy of Intravenous Fosfomycin in the Treatment of Complicated Urinary in Real-life Conditions. Impact of the CMI and Baseline Mutations. FOSFO-MIC Project
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Complicated Urinary Tract Infection
Keywords: Prospective follow-up study
Real-life conditions
Complicated urinary tract infection
Escherichia coli infection
Fosfomycin efficacy
Quinolones
Beta-lactams
Microbiological failure
Resistance development
Lead sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Sponsor class: OTHER
First posted: 2019-09-03
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patient with complicated urinary tract infection

Brief summary: This will be a prospective observational multicentre study in real-life conditions of patients with complicated urinary infection of community presentation caused by Escherichia coli using intravenous fosfomycin, quinolones or beta-lactams.

It's a multicenter and multinational study and it will include 200 patients in the fosfomycin cohort and 200 patients in the control cohort (quinolones or beta-lactams).

Detailed description: The objectives are:

1. To asses the clinical and microbiological efficacy and safety of intravenous fosfomycin in the treatment of complicated urinary tract infections due to Escherichia coli in real life conditions, in comparison with a matched cohort of patients treated with quinolones or beta-lactams.
2. To evaluate the frequency of microbiological failure and development of resistance (or decrease in sensitivity) in Escherichia coli isolates, depending on different pharmacokinetic and pharmacodynamic parameters, with special emphasis on fAUC0-24/MIC.
3. To evaluate the frequency of microbiological failure and development of resistance (or decrease in sensitivity) and their association with the existence of basal mutations in genes related to intracellular transport or regulation of these transporters.

For objective 1, a study of prospective mated cohorts (fosfomycin cohort versus quinolones or beta-lactams cohort) will be performed, and for objectives 2 and 3 a prospective cohort study (fosfomycin cohort) will be conducted.

Eligibility criteria: Fosfomycin cohort:

* Inclusion criteria: Patients over 18 years of age. Patients who have started treatment with intravenous fosfomycin, estimated that they will require at least 2 days of treatment with fosfomycin, initiated as either as empirical treatment (within 24 hours after the emergency visit or onset of symptoms) or targeted treatment (within 24 hours of the availability of the antibiogram).
* Exclusion criteria: Patients under 18 years of age. Patients in palliative treatment.

Control cohort (objective 1):

* Inclusion criteria:Patients over 18 years of age. Patients who have started treatment with intravenous quinolones or beta-lactams, estimated that they will require at least 2 days of treatment with the drug, initiated as either as empirical treatment (within 24 hours after the emergency visit or onset of symptoms) or targeted treatment (within 24 hours of the availability of the antibiogram). Each patient from the fosfomycin cohort will be matched with a patient from this control cohort according to their.
* Exclusion criteria: Patients under 18 years of age.Patients in palliative treatment; Informed consent not signed by the patient.

Primary outcomes:
measure: The difference in the proportion of subjects getting clinical-microbiological cure on the test of cure between the fosfomycin cohort and the quinolones or beta-lactams cohort
timeFrame: 21 days
measure: The proportion of microbiological failure on the test of cure in the fosfomycin cohort (measured as isolation of Escherichia coli in uroculture on the test of cure).
timeFrame: 21 days
measure: The proportion of development of resistance (or decrease in sensitivity) to fosfomycin during or after treatment: Presence of mutation in genes uhpT, uhpA, uhpB, uhpC, uhpT, crp, cyaA, ptsl and fosA and measure CMI.
timeFrame: 30 days
Secondary outcomes:
measure: To evaluate the frequency of microbiological failure and development of resistance (or decrease in sensitivity) in Escherichia coli isolates.
timeFrame: 30 days
measure: The difference in the proportion of solicited EAs in subjects in fosfomycin cohort and quinolones or beta-lactams cohort.
timeFrame: Day 5 through Day 21
Other outcomes:
Locations:
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
Study officials:
affiliation: Hospital Universitario Virgen Macarena
name: Belén Gutiérrez Gutiérrez
role: STUDY_DIRECTOR
References: