Comparison of efficacy and safety of ciprofloxacin otic solution 0.2% versus polymyxin B-neomycin-hydrocortisone in the treatment of acute diffuse otitis externa

ABSTRACT

Objective: To compare the efficacy and safety of ciprofloxacin otic solution 0.2% to polymyxin B-neomycin-hydrocortisone (PNH) otic solution in the treatment of acute diffuse otitis externa in children, adolescents, and adults.

Methods: This was a randomized, parallel-group, evaluator-blind, active-controlled, multicenter, noninferiority study. The primary efficacy endpoint was clinical cure of otitis symptoms at the test-of-cure (TOC) visit. Clinical cure at the end-of-treatment (EOT) visit and percentages of patients with clinical improvement and resolution and/or improvement of otalgia at EOT and TOC visits were secondary efficacy endpoints.

Results: A total of 630 patients were randomized to ciprofloxacin twice daily (n = 318) or PNH 3 times daily (n = 312) for 7 days. Ciprofloxacin was shown to be noninferior to PNH. The percentage of patients with clinical cure at the TOC visit was 86.6% with ciprofloxacin and 81.1% with PNH; the treatment difference was 5.6% in favor of ciprofloxacin (95% CI: −0.9 to 12.1). At the EOT visit, clinical cure was achieved in 70.0% and 60.5% of patients, respectively, with a treatment difference in favor of ciprofloxacin (9.5%, 95 CI: 1.2 to 17.9). In all secondary efficacy variables, ciprofloxacin and PNH showed similar results, including pain duration and resolution. The clinical cure rate for patients with baseline cultures showing P. aeruginosa was 87.5% in the ciprofloxacin group and 78.6% in the PNH group, a treatment difference of 8.9% in favor of ciprofloxacin (95% CI: 0.6 to 17.3); for patients with baseline cultures showing S. aureus, the clinical cure rate was 72.7% for the ciprofloxacin group and 75.9% for the PNH group (treatment difference of 3.1% in favor of PNH, 95% CI: −21.1% to 27.4%). Most adverse events were mild and unrelated to study medication in both treatment groups. A limitation of this study is the assessment of signs and symptoms at baseline and after treatment, which does not provide data to evaluate the interim response.

Conclusions: Ciprofloxacin otic solution 0.2% was found to be noninferior to PNH. This efficacy, good tolerability, and ease of administration make ciprofloxacin otic solution 0.2% without a topical steroid an attractive option for the treatment of acute otitis externa.

Key words: :

• Otitis externa
• Ciprofloxacin otic solution 0.2%
• Polymyxin B-neomycin-hydrocortisone otic solution
• Efficacy

Acknowledgements

Declaration of interest: The trial was undertaken with a research grant from Laboratorios SALVAT, S.A., Barcelona, Spain. All authors and investigators received investigator fees according to the number of patients accrued to the study.

The authors acknowledge the Medical Department at Laboratorios Salvat for their contributions to the study design and analysis of the data, and Robert Armstrong, MD of Ortho-McNeil Janssen Scientific Affairs, LLC, for his review of the manuscript and suggestions. The authors also thank Lisa Shannon and Roseanne Degnan of Scientific Connexions for providing editorial assistance on behalf of Laboratorios Salvat.

The authors are grateful to all the investigators who participated in the trial: Anthony Ciulla, Anthony Puopolo, Bethany Black, John Champlin, Blaise Congeni, Bradley Fox, Bradley Reese, Brian Bock, Charles Kistler, Craig Rose, Earl Franklin, Frank Mazzone, Gerald Shockley, Jack Seidel, James Hedgepeth, James Hedrick, James Kratzer, Jennifer Miles, Jerald Finnegan, Jerry Bernstein, John Crites, John Peniston, Josep Marés Bermúdez, Kevin Wingert, Leonel Limonte, Malcolm Sperling, Mark Bibler, Michael Hassman, Michelle Rose, Milo Hilty, Ned Rupp, Nicholas Knight, Norman Becker, Pere Plaja Román, Richard Nielsen, Richard Schwartz, Samuel McLinn, Sherman Alter, Steven Kaster, Steven Shapiro, Terry Brenneman, Thomas Fiel, Thomas Latiolais, William Jennings, William Johnston.

Notes

* Results from the pediatric subset of patients were presented at the American Society of Pediatric Otolaryngology annual meeting, Orlando, Florida, May 2–4, 2008, and at the Pediatric Academic Society annual meeting, Honolulu, Hawaii, May 3–6, 2008

* Cetraxal is a registered trade name of Laboratorios SALVAT, S.A., Barcelona, Spain

* Calgiswab is a registered trade name of Hardwood Products Co., Guilford, ME

* SAS Software is a registered trade name of SAS Institute Inc., Cary, NC