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

NCT ID: NCT02261506

Last Updated: 2017-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

115 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-10-16

Study Completion Date

2017-10-05

Brief Summary

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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

Detailed Description

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Conditions

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Bacteremia

Keywords

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Intensive care bacteremia bloodstream infection antimicrobial mortality antimicrobial stewardship

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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7 days

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

Group Type ACTIVE_COMPARATOR

7 days of adequate antibiotic treatment durations

Intervention Type 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.

14 days

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

Group Type ACTIVE_COMPARATOR

14 days of adequate antibiotic treatment durations

Intervention Type OTHER

Interventions

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7 days of adequate antibiotic treatment durations

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.

Intervention Type OTHER

14 days of adequate antibiotic treatment durations

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Kingston Health Sciences Centre

OTHER

Sponsor Role collaborator

Sunnybrook Health Sciences Centre

OTHER

Sponsor Role lead

Responsible Party

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Dr. Nick Daneman

Clinician Scientist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Nick Daneman, MD

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Health Sciences Centre

Locations

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Foothills Hospital

Calgary, Alberta, Canada

Site Status

University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status

Royal Columbian Hospital

Vancouver, British Columbia, Canada

Site Status

St. Paul's Hospital

Vancouver, British Columbia, Canada

Site Status

St. Boniface Hospital

Winnipeg, Manitoba, Canada

Site Status

Queen Elizabeth II Hospital

Halifax, Nova Scotia, Canada

Site Status

Kingston General Hospital

Kingston, Ontario, Canada

Site Status

London Health Sciences Centre

London, Ontario, Canada

Site Status

The Ottawa Hospital

Ottawa, Ontario, Canada

Site Status

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status

Mount Sinai Hospital

Toronto, Ontario, Canada

Site Status

St. Michael's Hospital

Toronto, Ontario, Canada

Site Status

Toronto Western Hospital

Toronto, Ontario, Canada

Site Status

CHUM

Montreal, Quebec, Canada

Site Status

Centre hospitalier affilié universitaire de Québec

Québec, Quebec, Canada

Site Status

CSSS de Trois-Rivières

Québec, Quebec, Canada

Site Status

Université de Sherbrooke

Sherbrooke, Quebec, Canada

Site Status

Countries

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Canada

References

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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.

Reference Type DERIVED
PMID: 29452598 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25903783 (View on PubMed)

Other Identifiers

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187-2014

Identifier Type: -

Identifier Source: org_study_id