Clinical trial NCT02261506: Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness: A Pilot RCT
Official title: Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness: A Pilot RCT
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Bacteremia
Keywords: Intensive care
bacteremia
bloodstream infection
antimicrobial
mortality
antimicrobial stewardship
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: Kingston Health Sciences Centre
First posted: 2014-10-10
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Bacteremia is a leading cause of mortality and morbidity in critically ill adults. Although bacteria in the bloodstream (bacteremia) may arise from variable infectious foci (most commonly central vascular catheter related, lung, urinary tract, intra-abdominal, or skin and soft tissue sources), because of the high attendant morbidity and mortality of bacteremia, these patients collectively represent a critically important group to study.

The consequences of the excessive antimicrobial use for individual patients, range from rash, gastrointestinal upset and diarrhea, to anaphylaxis, neutropenia, renal failure, toxic epidermal necrolysis, death, and a marked increase in ICU and hospital drug costs. One particularly concerning complication, Clostridium difficile infection, has increased in incidence and severity over the past decade. Much of this burden could be prevented through reduction in unnecessary antibiotic use.

Another major consequence of excessive antibiotic use is antimicrobial resistance. Antibiotic resistance is not only a concern for the patient who receives antibiotics, but also for neighbouring patients in the ICU, as well as future patients in the ICU and the hospital at large - through patient-to-patient transmission, and environmental contamination.

No previous randomized controlled trials have directly compared shorter versus longer durations of antimicrobial treatment in these patients. The investigators will conduct a multi-center randomized concealed allocation trial of shorter duration (7 days) versus longer duration (14 days) antibiotic treatment for critically ill patients with bacteremia admitted to ICU. Eligible, patients will be randomized to either 7 days or 14 days of adequate antimicrobial treatment. The selection of type, dose and route of antibiotics will be at the discretion of the treating physicians, but the duration of treatment (7 versus 14 days) will be determined by randomization group. The randomization assignment will not be communicated to the study research coordinator, study critical care or infectious diseases investigators or clinicians until day 8. The primary outcome for the main trial will be 90-day mortality.

The study will be initiated at Sunnybrook Health Sciences Centre in Toronto, Ontario, and then rolled out to a second site at Kingston General Hospital in Kingston, Ontario. These sites will be sufficient to meet the sample size goals for the pilot RCT, but if additional funds are obtained the investigators will also roll out to the other Canadian ICUs listed below. The goal of adding these additional sites will be to increase the generalizability of the findings with respect to trial feasibility


Eligibility criteria: Inclusion Criteria:

* Patient is in the ICU at time the blood culture result reported as positive AND
* Patient has a positive blood culture with pathogenic bacteria.

Exclusion Criteria:

* Patient already enrolled in the trial
* Patient has severe immune system compromise, as defined by: absolute neutrophil count \<0.5x109/L; or is receiving immunosuppressive treatment for solid organ or bone marrow or stem cell transplant
* Patient has syndrome with well-defined requirement for prolonged treatment:

  * infective endocarditis
  * osteomyelitis/septic arthritis
  * undrainable/undrained abscess
  * unremovable/unremoved prosthetic-associated infection
* Patient has a single positive blood culture with a common contaminant organism according to Clinical Laboratory \& Standards Institute (CLSI) Guidelines: coagulase negative staphylococci; or Bacillus spp.; or Corynebacterium spp.; or Propionobacterium spp.; or Aerococcus spp.; or Micrococcus spp.
* Patient has a positive blood culture with Staphylococcus aureus.
* Patient has a positive blood culture with Candida spp. or other fungal species.

Primary outcomes:
measure: Adherence to treatment duration protocol (proportion of treatment courses)
timeFrame: 15 days
measure: Rate of recruitment (patients per site, per month)
timeFrame: For up to 1 year
Secondary outcomes:
measure: ICU mortality
timeFrame: Recorded as alive or dead at ICU discharge following index positive blood culture for an expected average of 2 weeks assesses upto one year.
measure: Hospital mortality
timeFrame: recorded as alive or dead at hospital discharge following index positive blood culture for an expected average of 4 weeks assesses upto one year.
measure: 90 day mortality
timeFrame: Recorded as alive or dead at 90 days following index positive blood culture
measure: Relapse rates of bacteremia
timeFrame: Upto 30 days after adequate antibiotic treatment
measure: Antibiotic allergy
timeFrame: Up to 30 days from start of antibiotic treatment.
measure: Anaphylaxis
timeFrame: Up to 30 days from start of antibiotic treatment
measure: Antimicrobial-related acute kidney injury
timeFrame: Up to 30 days from start of antibiotic treatment
measure: Antimicrobial-related hepatitis
timeFrame: Up to 30 days from start of antibiotic treatment
measure: Rates of Clostridium difficile infection in hospital
timeFrame: Upto 30 days after index blood culture collection date
measure: Rates of secondary nosocomial infection with antimicrobial resistant organisms in hospital
timeFrame: Upto 30 days after index blood culture collection date
measure: ICU lengths of stay
timeFrame: For the duration of ICU stay, expected for an average of 30 days assessed up to 1 year.
measure: Hospital lengths of stay
timeFrame: For the duration of Hospital stay, expected for an average of 30 days assessed up to 1 year.
measure: Mechanical ventilation duration
timeFrame: For the duration of ICU and Hospital stay, expected for an average of 30 days
measure: Vasopressor duration in ICU
timeFrame: For the duration of ICU and Hospital stay, expected for an average of 30 days
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Foothills Hospital
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Royal Columbian Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: St. Boniface Hospital
state: Manitoba
city: Halifax
country: Canada
facility: Queen Elizabeth II Hospital
state: Nova Scotia
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
city: Montreal
country: Canada
facility: CHUM
state: Quebec
city: Sherbrooke
country: Canada
facility: Université de Sherbrooke
state: Quebec
city: Quebec
country: Canada
facility: Centre hospitalier affilié universitaire de Québec
city: Quebec
country: Canada
facility: CSSS de Trois-Rivières
Study officials:
affiliation: Sunnybrook Health Sciences Centre
name: Nick Daneman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Daneman N, Rishu AH, Pinto R, Aslanian P, Bagshaw SM, Carignan A, Charbonney E, Coburn B, Cook DJ, Detsky ME, Dodek P, Hall R, Kumar A, Lamontagne F, Lauzier F, Marshall JC, Martin CM, McIntyre L, Muscedere J, Reynolds S, Sligl W, Stelfox HT, Wilcox ME, Fowler RA; Canadian Critical Care Trials Group. 7 versus 14 days of antibiotic treatment for critically ill patients with bloodstream infection: a pilot randomized clinical trial. Trials. 2018 Feb 17;19(1):111. doi: 10.1186/s13063-018-2474-1.
citation: Daneman N, Rishu AH, Xiong W, Bagshaw SM, Cook DJ, Dodek P, Hall R, Kumar A, Lamontagne F, Lauzier F, Marshall JC, Martin CM, McIntyre L, Muscedere J, Reynolds S, Stelfox HT, Fowler RA; Canadian Critical Care Trials Group. Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE): study protocol for a pilot randomized controlled trial. Trials. 2015 Apr 18;16:173. doi: 10.1186/s13063-015-0688-z.