The Tobramycin Study

Cancer Clinical Trial

Official title:

Tobramycin én Gang Daglig Mot Tre Ganger Daglig, Gitt Med Benzylpenicillin, Til Pasienter Med nøytropen Feber

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00257790
• Other study ID #: Tobrax1
• Secondary ID: 01-0685085602016
• Status: Completed
• Phase: Phase 4
• First received: November 22, 2005
• Last updated: July 3, 2011
• Start date: September 2001
• Est. completion date: March 2005

Study information

• Verified date: November 2005
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Norway: Norwegian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 210
• Est. completion date: March 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 70 Years
• Eligibility: Febrile neutropenia Cancer Adult (16-70) Signed informed consent

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer
• Fever
• Neutropenia

Intervention

Drug:
• Tobramycin once a day

Locations

Country	Name	City	State
n/a

Sponsors (10)

Lead Sponsor	Collaborator
Oslo University Hospital	Sentralsjukehuset i Hedemark, Sentralsjukehuset i Rogaland, Sorlandet Hospital HF, Sykehuset Asker og Baerum, Sykehuset Buskerud, Sykehuset Innlandet HF, The Hospital of Vestfold, The National Institute of Health, Oslo, Ullevaal University Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Resolution of fever and signs of infection without modification of the antibiotic regimen
Secondary	Hours to defervescence
Secondary	Days to treatment failure
Secondary	30 days mortality
Secondary	Nephrotoxicity
Secondary	Other side effects
Secondary	Pharmacokinetics of tobramycin in febrile neutropenic patients
Secondary	Total antibiotic consumption
Secondary	Cost-benefit of giving tobramycin once a day vs three times a day