Official Title: “Tobramycin én Gang Daglig Mot Tre Ganger Daglig, Gitt Med Benzylpenicillin, Til Pasienter Med nøytropen Feber”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study

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(s) in this Clinical Trial

• Drug: Tobramycin once a day

Primary Measures

• Resolution of fever and signs of infection without modification of the antibiotic regimen

Secondary Measures

• Hours to defervescence
• Days to treatment failure
• 30 days mortality
• Nephrotoxicity
• Other side effects
• Pharmacokinetics of tobramycin in febrile neutropenic patients
• Total antibiotic consumption
• Cost-benefit of giving tobramycin once a day vs three times a day

• Febrile neutropenia Cancer Adult (16-70) Signed informed consent

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 16 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Rikshospitalet HF

Overall Clinical Trial Officials and Contacts

Dag Torfoss, MD Principal Investigator Rikshospitalet HF  

Information obtained from ClinicalTrials.gov on December 03, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00257790

Study ID Number: Tobrax1

ClinicalTrials.gov Identifier: NCT00257790

Health Authority: Norway: Norwegian Medicines Agency