Aminoglycosides for sepsis

Phase 1

• Conditions: Patients admitted with sepsis of unknown origin, suspected urinary origin or suspected abdominal origin; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2021-001840-83-NL
• Lead Sponsor: niversity Medical Center Utrecht

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-07-07
• Last Update Posted: 2 May 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 3140

Inclusion Criteria

1) Age >= 18 years
2) Presenting to the ER
3) Suspicion of bacterial infection of unknown origin, primary suspected urinary origin or primary suspected abdominal origin.
a. The working diagnosis set by the ER physician must state one of these three origin or ‘sepsis’ without mentioning a suspected focus
b. If there is no working diagnosis noted, the differential diagnosis should be assessed. If the differential diagnosis consist of urinary or abdominal infections only, a patient can participated in the study.
c. If the differential diagnosis is unclear, very wide (for example: Infection dd urinary tract infection dd pneumonia dd erysipelas dd abdominal focus) or clear, but mentions other origins besides urinary or abdominal, the local PI must be consulted (preferably within 3 days after admission). The PI determines whether patient should be included, depending on how likely a specific differential diagnosis is. If unclear, or very likely urological or abdominal, the patient can be included.
4) National Early Warning Score (NEWS) or Modified Early Warning Score (MEWS) = 5.
5) Requiring intravenous antibiotic treatment and hospitalization.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 3140
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3140

Exclusion Criteria

A potential subject who meets any of the following criteria will be excluded from participation in this study:
1) Working diagnosis at the ER of pneumonia.
2) Chemotherapy induced neutropenia as this is considered a separate entity in the guidelines.
3) Pre-existing renal failure defined as a GFR < 30, due to a relative contra-indication for aminoglycosides.
4) Allergy for cephalosporins or aminoglycosides, known prior to the start of treatment.
5) Indication for empirical coverage of ESBL-producing gram-negative bacteria according to the Dutch sepsis guidelines, i.e. known colonization or infection with ESBL-producing gram-negative bacteria in the prior year.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the impact of a treatment strategy consisting of cefuroxime + aminoglycoside as first-choice therapy compared to a strategy of ceftriaxone or cefuroxime monotherapy as first-choice therapy on 30-day all-cause mortality in patients with community-onset sepsis of unknown origin, suspected urinary origin, or suspected abdominal origin.;Secondary Objective: Secondary outcomes include duration of IC and hospital admission, quality of life, nephrotoxicity, ototoxicity and costs. In a cost-effectiveness analysis we will determine the costs per quality-adjusted life year gained.;Primary end point(s): 30-day all-cause mortality defined as mortality within 30 calendar days of the day of initial presentation to the ER, starting at day 0.;Timepoint(s) of evaluation of this end point: After day 30

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Duration of intravenous antibiotic treatment in calendar days and hours<br>•Time to switch to oral treatment in calendar days and hours<br>•Duration of hospitalization in calendar days <br>•ICU admission, length of ICU stay, mechanical ventilation <br>•ICU admission in patients who are not directly admitted to the ICU<br>•Complications during hospital admission possibly related to the disease or treatment (see Table 4)<br>•Nephrotoxicity requiring dialysis <br>•Hospital re-admission within 30 days of initial hospitalization<br>•Failure of treatment defined as switch of antibiotic treatment because patient is not improving clinically under current policy or because cultures have shown a pathogen that is not covert by the current antibiotic treatment. <br>;Timepoint(s) of evaluation of this end point: After day 30