Efficacy of Intravenous Fosfomycin in the Treatment of Complicated Urinary in Real-life Conditions.

Complicated Urinary Tract Infection Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04076436
• Other study ID #: FIS-FOS-2019-01
• Status: Recruiting
• Start date: October 21, 2019
• Est. completion date: December 31, 2021

Study information

• Verified date: August 2019
• Source: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Contact: Belén Gutiérrez Gutiérrez
• Phone: 955 00 80 00
• Email: belengutiguti[@]hotmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: December 31, 2021
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Complicated Urinary Tract Infection
• Infection
• Urinary Tract Infections

Intervention

Other:
• Drug: Intravenous fosfomycin
Patients will be visited on days 1 (Day of the urine and blood culture taking), 2, 5, 7, 14, on the test of cure and on day 30. Visit on day 1: First day of treatment. Basal data collection. Visit on day 2: Blood collection to fosfomycin levels calculation. Visits on days 5, 7, 14, on the test of cure (day 21): Clinical evolution data, Urocultures and Adverse effects. Visit on day 30: Assess mortality
• Drug: Intravenous quinolone or beta-lactam
Patients will be visited on days 1 (Day of the urine and blood culture taking), 5, 7, 14, on the test of cure and on day 30. Visit on day 1: First day of treatment. Basal data collection. Visits on days 5, 7, 14, on the test of cure (day 21): Clinical evolution data, Urocultures and Adverse effects. Visit on day 30: Assess mortality

Locations

Country	Name	City	State
Spain	Hospital Universitario Reina Sofía	Córdoba
Spain	Hospital Universitario Virgen Macarena	Sevilla

Sponsors (1)

Lead Sponsor	Collaborator
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	The difference in the proportion of subjects getting clinical-microbiological cure (disappearance of all new symptoms or signs related to urinary infection and negative uroculture) on the test of cure between the fosfomycin cohort and the quinolones or beta-lactams cohort	21 days
Primary	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).	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).	21 days
Primary	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.	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.	30 days
Secondary	To evaluate the frequency of microbiological failure and development of resistance (or decrease in sensitivity) in Escherichia coli isolates.	To evaluate the frequency of microbiological failure and development of resistance (or decrease in sensitivity) in Escherichia coli isolates.	30 days
Secondary	The difference in the proportion of solicited EAs in subjects in fosfomycin cohort and quinolones or beta-lactams cohort.	The difference in the proportion of solicited EAs in subjects in fosfomycin cohort and quinolones or beta-lactams cohort.	Day 5 through Day 21