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

• Published in: Clinical therapeutics Vol. 24; no. 4; pp. 605 - 615
• Main Authors: Sokol, William N., Sullivan, James G., Acampora, Matthew D., Busman, Todd A., Notario, Gerard F.
• Format: Journal Article
• Language: English
• Published: Belle Mead, NJ EM Inc USA 01.04.2002; Excerpta Medica
• Subjects: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - therapeutic use; Anti-Infective Agents - administration & dosage; Anti-Infective Agents - adverse effects; Anti-Infective Agents - therapeutic use; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Clarithromycin - administration & dosage; Clarithromycin - adverse effects; Clarithromycin - therapeutic use; clarithromycin extended-release; Community-Acquired Infections - diagnostic imaging; Community-Acquired Infections - drug therapy; Community-Acquired Infections - microbiology; community-acquired pneumonia; Delayed-Action Preparations; Double-Blind Method; Female; fluoroquinolone; Fluoroquinolones; Humans; Male; Medical sciences; Middle Aged; Naphthyridines - administration & dosage; Naphthyridines - adverse effects; Naphthyridines - therapeutic use; Pharmacology. Drug treatments; Pneumonia - diagnostic imaging; Pneumonia - drug therapy; Pneumonia - microbiology; Prospective Studies; Radiography; Treatment Outcome; trovafloxacin; community-acquired pneumonia; fluoroquinolone; trovafloxacin; clarithromycin extended-release; Human; Lung disease; Clarithromycin; Pneumonia; Trovafloxacin; Respiratory disease; Controlled release form; Treatment efficiency; Multicenter study; Oral administration; Macrolide; Antibiotic; Chemotherapy; Fluoroquinolone derivatives; Community acquired infection; Treatment; Double blind study; Dosage form; Antibacterial agent; Comparative study; Quinolone derivatives
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/S0149-2918(02)85136-0

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% ( 74 85 ) and 95% ( 63 66 ), respectively, and radiologic success rates were 95% ( 80 84 ) and 95% ( 63 66 ), respectively. There were no statistically significant differences between groups. In clinically and microbiologically evaluable patients, overall bacteriologic eradication rates were 89% ( 85 95 ) for clarithromycin ER and 96% ( 64 67 ) 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.