A prospective, double-blind, multicenter study comparing clarithromycin extended-release with trovafloxacin in patients with community-acquired pneumonia

Abstract Background: Treatment guidelines for community-acquired pneumonia (CAP) generally include use of a macrolide, a fluoroquinolone, or doxycycline, although there is some debate concerning the use of a fluoroquinolone. Objective: The efficacy and tolerability of a new once-daily, extended-release (ER) formulation of clarithromycin were compared with those of a fluoroquinolone, trovafloxacin, in the treatment of patients with CAP. Methods: This was a prospective, multicenter, double-blind, double-dummy, parallel-group trial in which outpatients were randomized to receive 7 days of once-daily treatment with either clarithromycin ER (two 500-mg tablets) or trovafloxacin (200 mg). Eligible patients were ≥18 years old with signs and symptoms of pneumonia, radiologic evidence of an acute infiltrate, and mild to moderate infection, as classified by the investigator. Results: One hundred seventy-six patients were randomized to study treatment. They were primarily white (88%) and equally distributed between the sexes (52% female). Their mean (±SD) age was 47.5 ± 16.2 years. Results were similar between treatment groups in rates of clinical cure, microbiologic cure, bacteriologic eradication, and radiologic success at the test-of-cure visit (14–21 days posttreatment) for both the per-protocol and intent-to-treat analyses. Among clinically evaluable patients, clinical cure rates for clarithromycin ER and trovafloxacin were 87% (7485) and 95% (6366), respectively, and radiologic success rates were 95% (8084) and 95% (6366), respectively. There were no statistically significant differences between groups. In clinically and microbiologically evaluable patients, overall bacteriologic eradication rates were 89% (8595) for clarithromycin ER and 96% (6467) for trovafloxacin, with no significant differences between groups. Both antibiotics demonstrated high eradication rates against target microorganisms. There were no clinically meaningful differences in the incidence of specific drug-related adverse events. The majority of drug-related adverse events (>90%) were considered mild or moderate and resolved without the need for additional treatment. Conclusions: Although the study was prematurely terminated, resulting in inadequate power to demonstrate equivalence, once-daily clarithromycin ER was effective and well tolerated in the treatment of ambulatory adult (age ≥18 years) outpatients with CAP.