Biomarker-guided duration of antibiotic treatment for sepsis

Not Applicable

• Conditions: Sepsis; Infections and Infestations; Sepsis, unspecified

• Registration Number: ISRCTN47473244
• Lead Sponsor: niversity of Manchester

Brief Summary

2023 Protocol article in https://doi.org/10.1177/17511437231169193 (added 23/05/2023)

Detailed Description

Not available

Study Timeline

• Study Start: 2017-07-14
• Last Update Posted: 24 June 2024
• Study Completion: 2025-01-31

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 2760

Inclusion Criteria

1. Hospitalised adult patients at least 18 years of age
2. Up to 24 hours of initiation of empiric intravenous antibiotic treatments for a suspicion of sepsis (i.e. suspected sepsis” – see trial definition below)
3. Likely to remain hospitalised and receiving intravenous antibiotic treatment for at least the next 72 hours
4. Requirement for critical care

Suspected sepsis definition: Within the context of this study, ‘suspected sepsis’ is defined as ‘acute organ dysfunction associated with suspected infection’ (1). The trialists do not mandate a definition for ‘acute organ dysfunction’ and patient information underpinning local clinical decisions will be captured as part of the Case Report Form (CRF) which will include the Sequential Organ Failure Assessment (SOFA) score.

Exclusion Criteria

Current exclusion criteria as of 05/02/2021:
1. More than 24 h since receiving first empiric intravenous antibiotic treatments for a suspicion of sepsis
2. Prolonged (greater than 21 days) antimicrobial therapy mandated (e.g. for endocarditis, cerebral/hepatic abscess, tuberculosis, osteomyelitis)
3. Severely immunocompromised (e.g. neutropenia, less than 500 neutrophils/µl)
4. All treatment for suspected sepsis likely to be stopped within 24 hours of its initiation because of futility
5. 5.Any patient given, or anticipated to receive an IL-6 receptor inhibitor drug (e.g. tocilizumab or sarilumab) during their acute hospital admission
6. Consent declined
7. Previously enrolled in this trial

_____

Previous exclusion criteria:
1. More than 24 h since receiving first empiric intravenous antibiotic treatments for a suspicion of sepsis
2. Prolonged (greater than 21 days) antimicrobial therapy mandated (e.g. for endocarditis, cerebral/hepatic abscess, tuberculosis, osteomyelitis)
3. Severely immunocompromised (e.g. neutropenia, less than 500 neutrophils/µl)
4. All treatment for suspected sepsis likely to be stopped within 24 hours of its initiation because of futility
5. Consent declined
6. Previously enrolled in this trial

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1. Primary clinical effectiveness outcome: total duration of antibiotic treatment to 28 days following randomisation (superiority) measured in days (24-hour time periods from randomisation)<br>2. Primary safety outcome: 28-day all-cause mortality (non-inferiority) following randomisation

Secondary Outcome Measures

Name	Time	Method
Secondary effectiveness and safety outcome measures to 28 days following randomisation:<br>1. Antibiotic dose, measured as Defined Daily Dose<br>2. Unscheduled care escalation/re-admission<br>3. Infection relapse/recurrence requiring further antibiotic treatment<br>4. Super-infection, defined as new infection at a different anatomical site<br>5. Suspected antibiotic adverse reactions<br>6. Time to ‘fit’ for hospital discharge