Pilot Study of the Utility of Empiric Antibiotic Therapy for Suspected ICU-Acquired Infection
Primary Purpose
Nosocomial Infection, Pneumonia, Systemic Inflammatory Response Syndrome
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Site-specific empiric regimens included: Meropenem
Piperacillin/tazobactam
Ciprofloxacin and cefazolin +/- metronidazole
Sponsored by
About this trial
This is an interventional treatment trial for Nosocomial Infection focused on measuring Infection, Empiric, Antibiotics, Nosocomial, Pyrexia, Leukocytosis, Resistance
Eligibility Criteria
Inclusion Criteria:
- In hospital > 72 hrs and in ICU > 24hrs, and
- Core temperature ≥38.5°C, or temperature ≥ 38.0°C with a WBC>12,000/mm3, or temperature ≤ 36.0°C with a WBC > 12,000/mm3
- Suspicion of infection
Exclusion Criteria:
- Age < 18 years
- Imminent death (within 24 hrs) or withdrawal of aggressive therapy
- Prosthetic heart valve or vascular graft
- Neutropenia (Absolute neutrophil count < 1000/mm3)
- Received > 16 hours of a broad spectrum antibiotic in the last 24 hours (3rd gen cephalosporin, fluoroquinolone, carbapenem, anti-pseudomonal penicillin) or any combination therapy
- History of allergic reaction to both study medications
New physical findings consistent with infection:
- Meningeal signs
- Peritonitis + free air on Abdo x-ray
- Soft tissue infection / cellulitis
- Murmur & suspicion of endocarditis
- Newly available (within past 24 hours) culture results consistent with infection
Sites / Locations
- University Health Network
Outcomes
Primary Outcome Measures
Feasibility: = % of eligible patients who were consented and randomized
Acceptability: = % of patients in each study arm who were switched to open label therapy prior to culture results
Secondary Outcome Measures
Mortality (14, 30, 90 day)
Microbial resistance patterns
ICU-free days
Antibiotic-free days
Change in organ dysfunction (MOD scores)
Full Information
NCT ID
NCT00438269
First Posted
February 17, 2007
Last Updated
February 21, 2007
Sponsor
Canadian Critical Care Trials Group
Collaborators
The Physicians' Services Incorporated Foundation
1. Study Identification
Unique Protocol Identification Number
NCT00438269
Brief Title
Pilot Study of the Utility of Empiric Antibiotic Therapy for Suspected ICU-Acquired Infection
Official Title
Appropriate Antimicrobial Therapy in Critical Care: A Pilot Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
February 2007
Overall Recruitment Status
Completed
Study Start Date
February 2003 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
March 2005 (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
Canadian Critical Care Trials Group
Collaborators
The Physicians' Services Incorporated Foundation
4. Oversight
5. Study Description
Brief Summary
Infection developing in the intensive care unit is a common complication of critical illness, but notoriously difficult to diagnose. A definite diagnosis based on the most reliable tests usually is not possible for at least two days. It is unclear what the optimal management approach should be while awaiting the results of diagnostic tests. In some circumstances, broad spectrum antibiotics are started with a plan to adjust them once the results of cultures are available. Observational studies show that this results in greater antibiotic use, and the risk of superinfection and resistance. In other circumstances, antibiotics may be withheld pending the results of cultures, a strategy that leads to a delay in therapy when cultures are positive, and that may be associated with a worse clinical outcome.
We undertook a randomized pilot study to address the question: "In a critically ill patient for whom clinicians are uncertain whether infection may be present, and in whom potential sites of infection have been managed by removing or changing invasive devices, can a policy of delaying antibiotic treatment until cultures are available reduce the risks of excessive antibiotic use, without increasing the risks associated with delayed therapy?"
Recognizing that the question has not been formally addressed before, and that approaches to clinical management are both widely divergent and passionately held, our pilot study tested the feasibility and acceptability of undertaking a larger trial with sufficient power to determine equivalence.
Detailed Description
We randomized critically ill patients who had been in hospital for at least 72 hours, and in the ICU for at least 24 hours, and who manifested either a temperature >38.5 degrees, or a temperature>38.0 degrees and a white cell count >12,000, and in whom clinicians entertained the possibility of infection as a diagnosis, to either site-specific broad spectrum empiric antibiotics or the corresponding placebo. All patients underwent a comprehensive series of investigations to identify an infectious focus, and all patients had full source control, including changes of central lines and urinary catheters, and change of nasogastric to orogastric tubes.
Patients were maintained in assigned study arm for seven days, or until culture data were available, at which time they were switched to culture-guided narrow spectrum therapy
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nosocomial Infection, Pneumonia, Systemic Inflammatory Response Syndrome, Critical Illness, Pyrexia
Keywords
Infection, Empiric, Antibiotics, Nosocomial, Pyrexia, Leukocytosis, Resistance
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
80 (false)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Site-specific empiric regimens included: Meropenem
Intervention Type
Drug
Intervention Name(s)
Piperacillin/tazobactam
Intervention Type
Drug
Intervention Name(s)
Ciprofloxacin and cefazolin +/- metronidazole
Primary Outcome Measure Information:
Title
Feasibility: = % of eligible patients who were consented and randomized
Title
Acceptability: = % of patients in each study arm who were switched to open label therapy prior to culture results
Secondary Outcome Measure Information:
Title
Mortality (14, 30, 90 day)
Title
Microbial resistance patterns
Title
ICU-free days
Title
Antibiotic-free days
Title
Change in organ dysfunction (MOD scores)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
In hospital > 72 hrs and in ICU > 24hrs, and
Core temperature ≥38.5°C, or temperature ≥ 38.0°C with a WBC>12,000/mm3, or temperature ≤ 36.0°C with a WBC > 12,000/mm3
Suspicion of infection
Exclusion Criteria:
Age < 18 years
Imminent death (within 24 hrs) or withdrawal of aggressive therapy
Prosthetic heart valve or vascular graft
Neutropenia (Absolute neutrophil count < 1000/mm3)
Received > 16 hours of a broad spectrum antibiotic in the last 24 hours (3rd gen cephalosporin, fluoroquinolone, carbapenem, anti-pseudomonal penicillin) or any combination therapy
History of allergic reaction to both study medications
New physical findings consistent with infection:
Meningeal signs
Peritonitis + free air on Abdo x-ray
Soft tissue infection / cellulitis
Murmur & suspicion of endocarditis
Newly available (within past 24 hours) culture results consistent with infection
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mary-Anne W Aarts, MD MSc
Organizational Affiliation
University of Toronto
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
John C Marshall, MD
Organizational Affiliation
University of Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
Pilot Study of the Utility of Empiric Antibiotic Therapy for Suspected ICU-Acquired Infection
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