Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness: A Pilot RCT

NCT02261506 | Completed

• 1 other identifier: 187-2014
• Study Type: interventional
• Target: 115
• Locations: 1 country
• Sites: 17

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

Conditions

Bacteremia

Keywords

Intensive care; bacteremia; bloodstream infection; antimicrobial; mortality; antimicrobial stewardship

Outcome Measures

Primary Outcomes (2)

• Adherence to treatment duration protocol (proportion of treatment courses)

  We will consider the main trial to be feasible and worthy of embarking on a larger mortality-powered RCT if 90% of antibiotic treatment courses are within 7± 2 days in the shorter duration treatment arm or 14 ± 2 days in the longer duration treatment arm.

  15 days

• Rate of recruitment (patients per site, per month)

  We will consider the main trial to be feasible if we achieve recruitment rates of at least 1 patient per 4 weeks, on average, per participating site.

  For up to 1 year

Secondary Outcomes (14)

• ICU mortality

  Recorded as alive or dead at ICU discharge following index positive blood culture for an expected average of 2 weeks assesses upto one year.

• Hospital mortality

  recorded as alive or dead at hospital discharge following index positive blood culture for an expected average of 4 weeks assesses upto one year.

• 90 day mortality

  Recorded as alive or dead at 90 days following index positive blood culture

• Relapse rates of bacteremia

  Upto 30 days after adequate antibiotic treatment

• Antibiotic allergy

  Up to 30 days from start of antibiotic treatment.

Study Arms (2)

7 days

ACTIVE COMPARATOR

Patients in 7 day arm will receive adequate antibiotics until the end of day 7 only

Other: 7 days of adequate antibiotic treatment durations

14 days

ACTIVE COMPARATOR

Patients in 14 day arm will receive adequate antibiotics until the end of day 14 only

Other: 14 days of adequate antibiotic treatment durations

Interventions

7 days of adequate antibiotic treatment durations OTHER

We will not be randomizing patients to any specific antibiotic regimen. Patients will be randomized to fixed durations of adequate treatment: 7 versus 14 days. The selection of antibiotic(s) will be at the discretion of the treating team, although the research team will check to ensure that the selected antibiotics have an 'adequate' spectrum of coverage for the bacterial pathogen(s) isolated in the blood culture.

7 days

14 days of adequate antibiotic treatment durations OTHER

14 days

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• Kingston Health Sciences Centre: collaborator

Study Sites (17)

Foothills Hospital

Calgary, Alberta, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, Canada

Location

Royal Columbian Hospital

Vancouver, British Columbia, Canada

Location

St. Paul's Hospital

Vancouver, British Columbia, Canada

Location

St. Boniface Hospital

Winnipeg, Manitoba, Canada

Location

Queen Elizabeth II Hospital

Halifax, Nova Scotia, Canada

Location

Kingston General Hospital

Kingston, Ontario, Canada

Location

London Health Sciences Centre

London, Ontario, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N3M5, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, Canada

Location

St. Michael's Hospital

Toronto, Ontario, Canada

Location

Toronto Western Hospital

Toronto, Ontario, Canada

Location

CHUM

Montreal, Quebec, Canada

Location

Centre hospitalier affilié universitaire de Québec

Québec, Quebec, Canada

Location

CSSS de Trois-Rivières

Québec, Quebec, Canada

Location

Université de Sherbrooke

Sherbrooke, Quebec, Canada

Location

Related Publications (2)

• 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.

  PMID: 29452598 DERIVED

• 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.

  PMID: 25903783 DERIVED

MeSH Terms

Conditions

Bacteremia; Sepsis

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Nick Daneman, MD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinician Scientist

Study Record Dates

• First Submitted: September 26, 2014
• First Posted: October 10, 2014
• Study Start: October 16, 2014
• Primary Completion: August 30, 2017
• Study Completion: October 5, 2017
• Last Updated: December 18, 2017

Record last verified: 2017-12

Locations

CA (17)