Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE): study protocol for a pilot randomized controlled trial

Nick Daneman, Asgar H Rishu, Wei Xiong, Sean M Bagshaw, Deborah J Cook, Peter Dodek, Richard Hall, Anand Kumar, Francois Lamontagne, Francois Lauzier, John C Marshall, Claudio M Martin, Lauralyn McIntyre, John Muscedere, Steven Reynolds, Henry T Stelfox, Robert A Fowler, Canadian Critical Care Trials Group, Nick Daneman, Asgar H Rishu, Wei Xiong, Sean M Bagshaw, Deborah J Cook, Peter Dodek, Richard Hall, Anand Kumar, Francois Lamontagne, Francois Lauzier, John C Marshall, Claudio M Martin, Lauralyn McIntyre, John Muscedere, Steven Reynolds, Henry T Stelfox, Robert A Fowler, Canadian Critical Care Trials Group

Abstract

Background: Bacteremia is a leading cause of mortality and morbidity in critically ill adults. No previous randomized controlled trials have directly compared shorter versus longer durations of antimicrobial treatment in these patients.

Methods/design: This is a multicenter pilot randomized controlled trial in critically ill patients with bacteremia. Eligible patients will be adults with a positive blood culture with pathogenic bacteria identified while in the intensive care unit. Eligible, consented patients will be randomized to either 7 days or 14 days of adequate antimicrobial treatment for the causative pathogen(s) detected on blood cultures. The diversity of pathogens and treatment regimens precludes blinding of patient and clinicians, but allocation concealment will be extended to day 7 and outcome adjudicators will be blinded. The primary outcome for the main trial will be 90-day mortality. The primary outcome for the pilot trial is feasibility defined by (i) rate of recruitment exceeding 1 patient per site per month and (ii) adherence to treatment duration protocol ≥ 90%. Secondary outcomes include intensive care unit, hospital and 90-day mortality rates, relapse rates of bacteremia, antibiotic-related side effects and adverse events, rates of Clostridium difficile infection, rates of secondary infection or colonization with antimicrobial resistant organisms, ICU and hospital lengths of stay, mechanical ventilation and vasopressor duration in intensive care unit, and procalcitonin levels on the day of randomization, and day 7, 10 and 14 after the index blood culture.

Discussion: The BALANCE pilot trial will inform the design and execution of the subsequent BALANCE main trial, which will evaluate shorter versus longer duration treatment for bacteremia in critically ill patients, and thereby provide an evidence basis for treatment duration decisions for these infections.

Trial registration: The Pilot Trial was registered on 26 September 2014.

Trial registration number: NCT02261506.

Figures

Figure 2
Figure 2
Determination of day 7 of antibiotic treatment. Multiple scenarios are provided to determine how day 7 of antibiotic treatment will be determined based on days of receipt of adequate antibiotic treatment after collection of the positive blood culture. Adequacy of treatment will only be measurable after the culture and susceptibility result has been finalized.
Figure 1
Figure 1
BALANCE pilot RCT intervention flow diagram.

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