The Tobramycin Study
Condition: Neutropenia; Fever; Cancer
MeSH terms: Neutropenia
Study type: Interventional
Phase: Phase 4

Summary: 
      Evaluate if tobramycin given once a day is at least as efficacious as the traditional
      tobramycin given three times a day, given with penicillin G, til patients with febrile
      neutropenia.
    

Detailed description: 
      Prospective randomized Norwegian multicenter clinical trial (11 hospitals) comparing
      tobramycin given once a day (new regimen) vs. three times a day (current regimen), with
      penicillin G, to cancer patients with febrile neutropenia. Tobramycin half life and
      postantibiotic effect is at best 12 hours. It has been questioned if tobramycin once a day is
      safe in patients with low levels of granulocytes when it is given with a drug like penicillin
      G which is not covering Gram-negative rods. Treatment of febrile neutropenia with penicillin
      G and an aminoglycoside is standard of care in Norway, and it is probably a regimen that is
      promoting antimicrobial resistance less than a broad spectrum beta-lactam.

      Cancer patients 16-70 with febrile neutropenia and signed informed consent could be
      randomized. Exclusion criteria were allergy to study medications, increased creatinine/renal
      failure, massive ascites, multiple myeloma, treatment with cis-platinum, recent therapy with
      aminoglycoside (4 weeks) or other antibiotics (4 days), hemodynamically unstable patients,
      pregnant and nursing patients.

      Patients were stratified into three groups: Leukemia patients receiving intensive
      chemotherapy, lymphoma patients receiving high dose chemotherapy with autologous stem-cell
      support and other cancer patients.

      Patients were randomized to either tobramycin once or three times a day. Once the patient was
      randomized and the first antibiotic dose was given, further antibiotic therapy was up to the
      patient's doctor's discretion (not blinded). Everybody received tobramycin 6 mg/kg/day and
      penicillin 5 mill. IE four times a day.

      The patients were followed until all antibiotic therapy was terminated. Clinical condition
      and laboratory test results at time of randomization (new fever) was registered. Response to
      therapy, reason for modification of therapy, mortality, duration of neutropenia, maximum
      creatinine level, tobramycin serum concentrations, microbiological findings and total
      antibiotic consumption were registered.

      After external monitoring of all the data the results are currently being made up and will be
      available for publication in 2006.

      This trial has been conducted independently of the pharmaceutical industry. Grants have been
      received from The Norwegian Radium Hospital research fund, The Regional Health Authorities
      and The Norwegian Society for Infectious Diseases.
    

Intervention name(s): Tobramycin once a day
Intervention type(s): Drug
Intervention MeSH terms: Tobramycin
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Fever; Neutropenia; Tobramycin; Aminoglycoside; Penicillin