Comparison of the efficacy of extendled-release clarithromycin tablets andamoxicillin/clavulanate tablets in the treatment of acute exacerbation of chronic bronchitis

Background: Clarithromycin has established efficacy and safety in the treat ment of respiratory infections. Objective: This study examined the efficacy and safety of a new extended-re lease formulation of clarithromycin compared with amoxicillin/clavulanate i n the treatment of acute exacerbation of chronic bronchitis (AECB). Methods: This phase IIIB, multicenter, randomized, parallel-group, investig ator-blinded study in patients with AECB and productive cough with purulent sputum compared treatment with extended-release clarithromycin (two 500-mg tablets once daily for 7 days) and amoxicillin/clavulanate (one 875-mg tab let twice daily for 10 days). Assessments were performed before treatment, between study days 10 and 12 (or within 48 hours after premature discontinu ation), and between study days 17 and 21 (test of cure). Results: Of 287 patients randomized and treated, 270 were clinically evalua ble (137 clarithromycin, 133 amoxicillin/clavulanate). Treatment groups wer e well matched in terms of demographic characteristics, medical condition, and history. Among clinically evaluable patients at test of cure, 85% and 8 7% of clarithromycin- and amoxicillin/clavulanate-treated patients, respect ively, demonstrated clinical cure (as defined in 1998 draft US Food and Dru g Administration guidelines); among clinically and bacteriologically evalua ble patients, 92% versus 89%, respectively, demonstrated bacteriologic cure . Overall pathogen eradication rates were similar in the 7 groups; (88% cla rithromycin, 89% amoxicillin/clavulanate). Rates of premature discontinuati on of study drug for any reason differed between treatments: 3% (4/142) of clarithromycin-treated patients versus 12% (17/145) of amoxicillin/clavulan ate-treated patients (P = 0.005). One percent (2/142) and 6% (8/145) of the respective treatment groups discontinued study drug because of adverse eve nts. Adverse events generally occurred with a similar frequency in the 2 gr oups; however, taste alteration was more common with clarithromycin (9/142 [6%]) than with amoxicillin/clavulanate (1/145 [1%]; P = 0.01). Mean severi ty scores for gastrointestinal adverse events showed a significant differen ce between groups (1.16 for clarithromycin-treated patients and 1.58 for am oxicillin/clavulanate-treated patients; P = 0.016). Conclusions: The results of this study demonstrate the clinical and bacteri ologic equivalence and improved gastrointestinal tolerability of a 7-day co urse of once-daily extended-release clarithromycin relative to a 10-day cou rse of twice-daily amoxicillin/clavulanate in the treatment of AECB.