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Pilot Study of the Utility of Empiric Antibiotic Therapy for Suspected ICU-Acquired Infection

This study has been completed.
Sponsor:
Collaborator:
The Physicians' Services Incorporated Foundation
Information provided by:
Canadian Critical Care Trials Group
ClinicalTrials.gov Identifier:
NCT00438269
First received: February 17, 2007
Last updated: February 21, 2007
Last verified: February 2007

February 17, 2007
February 21, 2007
February 2003
Not Provided
  • 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
Same as current
Complete list of historical versions of study NCT00438269 on ClinicalTrials.gov Archive Site
  • Mortality (14, 30, 90 day)
  • Microbial resistance patterns
  • ICU-free days
  • Antibiotic-free days
  • Change in organ dysfunction (MOD scores)
Same as current
Not Provided
Not Provided
 
Pilot Study of the Utility of Empiric Antibiotic Therapy for Suspected ICU-Acquired Infection
Appropriate Antimicrobial Therapy in Critical Care: A Pilot Randomized Controlled Trial

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.

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

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
  • Nosocomial Infection
  • Pneumonia
  • Systemic Inflammatory Response Syndrome
  • Critical Illness
  • Pyrexia
  • Drug: Site-specific empiric regimens included: Meropenem
  • Drug: Piperacillin/tazobactam
  • Drug: Ciprofloxacin and cefazolin +/- metronidazole
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
80
March 2005
Not Provided

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00438269
AATICC Pilot Study
Not Provided
Not Provided
Canadian Critical Care Trials Group
The Physicians' Services Incorporated Foundation
Principal Investigator: Mary-Anne W Aarts, MD MSc University of Toronto
Principal Investigator: John C Marshall, MD University of Toronto
Canadian Critical Care Trials Group
February 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP