Active substances: Amoxicillin
The second-generation cephalosporin, cefuroxime axetil, is a semi-synthetic broad-spectrum oral antibiotic which is widely used for the treatment of respiratory tract infections.
The aim of this randomized, double-blind study was to compare the efficacy and tolerability of two different doses of levofloxacin 250 or 500 mg od with cefuroxime axetil 250 mg bd in the treatment of AECB in adult patients.
Materials and methods Study design and patients This randomized, double-blind study was carried out in 71 centres in 14 countries in Europe, Africa and South America.
Randomization was performed by centre, with each centre assigned a sequence of patient numbers. Study medication was randomly assigned to the patient numbers in advance by Hoechst Marion Roussel and labelled with the patient number.
Patients were numbered consecutively in the order in which they entered the study. Levofloxacin 250 and 500 mg and cefuroxime axetil were randomized on a 1:1:1 basis.
Study medication was supplied on blister cards consisting of a transparent strip and an opaque, plain, silver-foil strip and packed for 7 days' treatment in 24 h periods. For each 24 h period, the first dose consisted of one active tablet and two matching placebo tablets and the second dose comprised either one cefuroxime axetil tablet, for levofloxacin patients, one placebo tablet matching cefuroxime axetil.
Their symptoms and signs were compatible with the usual diagnosis criteria for AECB e. Patients were also excluded if they required probenecid or a systemic antibiotic for another infection or if they had received antibiotic treatment in the 72 h before entry to the study or azithromycin in the 7 days before study entry.
All patients provided informed consent, and the study protocol was approved for all centres by the local ethics committee. Patients were randomized to receive oral levofloxacin 250 mg od or 500 mg od Hoechst Marion Roussel, Frankfurt, Germany, or cefuroxime axetil 250 mg bd Glaxo Wellcome Ltd, Uxbridge, UK for 7- 10 days.
The primary analysis of efficacy was based on the clinical response in patients with bacteriologically confirmed AECB, determined at the clinical endpoint, 5- 14 days after the end of therapy per-protocol population.
Assessments A total of 832 patients were randomized to receive oral levofloxacin 250 mg od or 500 mg od or oral cefuroxime axetil 250 mg bd for 7- 10 days.
Assessments were performed after 3- 6 days of treatment and within 2 days post-treatment, 5- 14 days clinical endpoint and 21- 28 days follow-up after the end of treatment.
Assessments were made both by computer protocol assessment and by the investigator. All patients provided a detailed medical history and underwent a full physical examination and a postero-anterior chest X-ray to rule out pneumonia and bronchopneumonia at inclusion.
Clinical signs and symptoms of infection cough, peak flow spirometry, dyspnoea, sputum volume, sputum purulence and peak body temperature in febrile patients and bacteriological variables patient response, baseline pathogen response and pathogen sensitivity were documented at each visit.
Baseline sputum cultures were obtained from 3 days before to 2 days after the start of treatment in order to isolate and identify the causative pathogen and to examine for the presence of polymorphonuclear leucocytes and squamous epithelial cells.
Follow-up cultures were obtained at each visit. Haematology and serum chemistry were performed according to standard methods used at individual centres.
Safety was assessed at each visit by adverse events and vital signs; another physical examination was performed within 2 days after the end of treatment and laboratory parameters were assessed after 3- 6 days of treatment and within 2 days after the end of treatment.
Adverse events were classified by the investigators according to their intensity mild, moderate or severe, nature serious or non-serious and possible relationship to the study drug.
In the case of a serious adverse event possibly related to the study drug investigator assessment, patients were immediately withdrawn from the study if still on the study drug.
An adverse event was serious if it was fatal or life-threatening, permanently or significantly disabling, required prolonged hospitalization, involved cancer or congenital anomaly, occurred as a result of overdose or suggested a significant hazard.
Analyses Analyses were performed on the intention-to-treat ITT population all patients who received at least one dose of medication and the per-protocol population all patients with clinical signs and symptoms of infection and bacteriologically proven infection, excluding major protocol violators.