The MOSAIC study: A multicenter, multinational, randomized, double-blind study to compare moxifloxacin oral tablets to standard oral antibiotic regimen given as first-line therapy in outpatients with acute infective exacerbations of chronic bronchitis. The MOSAIC study is unique and improved in its design. Specifically, it includes: established pre-exacerbation baseline; multicomparator, randomized, double-blind study; and short- and long-term follow-up. MOSAIC has been submitted to CHEST for publication and is currently under review.
1,935 patients with chronic bronchitis were enrolled while stable. Data were collected on patient age, smoking status, concomitant medication use, lung function, severity and duration on chronic bronchitis. 733 patients had an exacerbation and were randomized into either 5 day oral moxifloxacin 400 mg qd, or a 7b day comparator: amoxicillin 500 mg tid, clarithromycin 500 mg bid, or cefuroxime axetil 250 mg bid.Investigators could preselect their choice of comparator. Primary endpoint was clinical success at 7 - 10 days posttreatment. Patient’s need for additional antimicrobial therapy was assessed at 7 - 10 days posttreatment. Long-term follow-up was recorded time until next AECB episode. Study included 103 centers in 19 countries throughout the world. Countries included: Austria, Belgium, Finland, France, Germany, Greece, Hungry, Norway, Poland, Portugal, Slovenia, Spain, Switzerland, United Kingdom, Israel, Mexico, Argentina, Brazil, and Australia.
RESULTS and CLINICAL IMPLICATIONS:
In patients with AECB, moxifloxacin demonstrated significantly higher bacteriological success rates. Among patients of the per protocol population with sputum samples both before and after treatment, 65/71 (91.5%) patients receiving moxifloxacin and 64/79 (81.0%) on comparator showed bacteriological success. This was statistically significant (95% CI; 0.4, 22.05). There was significantly greater clinical resolution after 5 days of treatment with moxifloxacin vs 7 days of comparator. Clinical cure was seen in 251/354 (71.0%) patients in the moxifloxacin and 236/376 (63.0%) in the comparator of the ITT population (95% CI: 1.4, 14.9 p=0.05), and 191/274 (70%) vs 185/298 (62%) in the per protocol population (95% CI; 0.3, 15.6; p=0.02). Significantly fewer moxifloxacin patients required additional antimicrobial therapy than the comparator group during the follow-up period. In both the ITT and per protocol populations, significantly higher proportions of patients in the comparator (15% and 15% in the two populations) required further antibiotic treatment than in the moxifloxacin (9% and 10%, p=0.006 and 0.050). Significantly prolonged AECB-free interval mean (SD) times to the next AECB were 132.8 (67.5) days and 118.0 (67.9) days for the moxifloxacin and comparator, respectively, and the difference was statistically significant (p=0.03).
PP PopulationMoxifloxacin (n=274)Comparator (n=298)p ValueAge, yrs mean (SD)84.5 (9.7)62.5 (9.8)0.01Comorbidity, n (%)199 (72.6)223 (74.8)0.69Sex, n (%) male190 (69.3)202 ((67.8)0.72 female (%)84 (30.7)96 (32.2)Duration of smoking exposure, yrs, mean (SD)37.7 (11.2)38.1 (10.9)0.74Duration of chronic bronchitis, yrs12.5 (10.0) 12.9 (10.1)0.78 ≥10, n (%)144 (52.6)166 (55.7)Number of AECBs in the last year, n (%)204 (74.5)218 (73.2)0.72 2-370 (25.5)80 (26.8) ≥4