Pooled analysis of two clinical trials comparing the clinical outcomes of topical ciprofloxacin/dexamethasone otic suspension and polymyxin B/neomycin/hydrocortisone otic suspension for the treatment of acute otitis externa in adults and children

Abstract

Objective: This study aimed to compare the clinical outcome of patients receiving topical ciprofloxacin 0.3%/dexamethasone 0.1% (CD) otic suspension with that of those receiving polymyxin B/neomycin/ hydrocortisone (PNH) otic suspension for the treatment of acute otitis externa (AOE). Methods: Data from 2 institutional review board-approved, multicenter, observer-masked, parallel-group, randomized, noninferiority clinical trials conducted at 76 institutions across the United States between April 1998 and July 1999 were pooled together for this analysis. Patients ≥1 year of age diagnosed with AOE were considered for inclusion in the studies. Patients with AOE >4 weeks' duration, a perforated tympanic membrane, chronic suppurative otitis media, or use of either antibiotics or steroids within the previous 7 days were excluded from the studies. Patients were randomly assigned to receive CD or PNH for 7 days. CD was administered as 3 drops in children and 4 drops in patients ≥12 years of age BID. PNH was administered as 3 drops in children and 4 drops in patients ≥12 years of age TID. The clinical investigators were blinded to treatment assignment. Due to the different dosing regimens, patients were not blinded, but they also were not directly informed of their treatment assignments. Otic inflammation, tenderness, edema, and discharge were clinically assessed on days 3, 8, and 18 of the studies. Otic inflammation and edema were evaluated using a 4-point scale (none = 0; mild = 1; moderate = 2; and severe = 3). Otic tenderness and discharge were rated on a binomial scale (absent = 0 and present = 1). The clinical assessments were aggregated into a 9-point composite clinical scale (range, 0-8) to compare baseline severity between groups. For the final outcomes assessment in this study, the aggregated clinical scores were dichotomized into cured (0) versus noncured (>0) and analyzed using a Kaplan-Meier survival technique. A log-rank test was used to compare the cure curves between treatment groups. Kaplan-Meier summary statistics provide the mean and median times to cure, and the mean times to cure for the 25th and 75th patient quartiles. Tolerability was assessed by monitoring patients for adverse events at each visit. Results: Data from 1072 patients (1242 ears) were included in the analysis (CD, 537 patients; PNH, 535 patients). Baseline AOE severity and demographic characteristics were similar between the 2 treatment groups. The mean patient age was 21.7 and 22.0 years in the CD and PNH groups, respectively. Both groups were similar with respect to sex, with 50.7% and 53.5% females in the CD and PNH groups, respectively. The racial composition was predominately white (88.6% vs 84.9% in the CD and PNH groups, respectively). The log-rank test revealed a significant difference in the AOE cure curves between the CD and PNH groups (P = 0.038). The proportions cured in the AOE at-risk groups at the day-3, -8, and -18 assessments in the CD and PNH treatment groups were 0.14 and 0.10, 0.75 and 0.72, and 0.98 and 0.97, respectively. The Kaplan-Meier summary statistics indicated that the mean time to cure was 0.6 day less with CD compared with PNH (9.7 vs 10.3 days). Treatment-related adverse event rates were similar between the 2 groups and occurred in 3.8% of the patients. The most common adverse events included otic pruritus (2.1%), otic congestion (0.6%), otic debris (0.5%), otic pain (0.3%), superimposed ear infection (0.3%), and erythema (0.1%). Conclusion: These data from 2 previous studies suggest that time to cure was significantly less with CD compared with PNH in patients with AOE.