title: Phase 3 Trials of Thermosensitive Ciprofloxacin Gel for Middle Ear Effusion in Children with Tubes.
abstract: To investigate the efficacy, safety, and microbiology of a thermosensitive otic suspension of ciprofloxacin (OTO-201) in children with bilateral middle ear effusion undergoing tympanostomy tube placement.
  
  
  
  Two randomized, double-blind, sham-controlled phase 3 trials. Patients were randomized to intratympanic OTO-201 or sham.
  
  
  
  Children with bilateral middle ear effusion undergoing tympanostomy tube placement.
  
  
  
  Studies evaluated 532 patients (6 months to 17 years old) in a combined analysis of efficacy (treatment failure: presence of otorrhea, otic or systemic antibiotic use, lost to follow-up, missed visits), safety (audiometry, otoscopy, tympanometry), and microbiology.
  
  
  
  There was a lower cumulative proportion of treatment failures in patients receiving OTO-201 vs tympanostomy tubes alone (1) on days 4, 8, 15, and 29; (2) on day 15, primary end point (23.0% vs 45.1%; age-adjusted odds ratio, 0.341; P < .001; reduction in relative risk, 49%); and (3) on day 15, blinded-assessor otorrhea treatment failure (7.0% vs 19.4%; age-adjusted odds ratio, 0.303; P < .001; reduction in relative risk, 64%). Per-protocol and subgroup analyses (baseline demographics, pathogen type, culture status, effusion type, microbiologic response) supported these findings. There were no drug-related serious adverse events; the most frequent treatment-emergent adverse events in both groups were pyrexia, postoperative pain, nasopharyngitis, cough, and upper respiratory tract infection. OTO-201 administration had no evidence of increased tube occlusion and no negative effect on audiometry, tympanometry, or otoscopy.
  
  
  
  Combined analysis of 2 phase 3 trials demonstrated a lower cumulative proportion of treatment failures through day 15 compared with TT alone when OTO-201 was administered intratympanically for otitis media with bilateral middle ear effusion at time of tympanostomy tube placement.
authors.affiliation: Department of Surgery and Pediatrics, University of Utah, Salt Lake City, Utah, USA albert.park@imail2.org.
authors.forename: Albert H
authors.initials: AH
authors.lastname: Park
authors.affiliation: Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: White
authors.affiliation: Charlotte Eye, Ear, Nose, and Throat Associates, Charlotte, North Carolina, USA.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Moss
authors.affiliation: Forsythe and Bear, LLC, Woodlands, California, USA.
authors.forename: Moraye
authors.initials: M
authors.lastname: Bear
authors.affiliation: Otonomy, Inc, San Diego, California, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: LeBel
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D002939:Ciprofloxacin / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005782:Gels; D006801:Humans; D007223:Infant; D008297:Male; D008876:Middle Ear Ventilation; D010034:Otitis Media with Effusion / Q000188:drug therapy* / Q000382:microbiology / Q000601:surgery*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D005782:Gels; D002939:Ciprofloxacin
keywords: OTO-201; ciprofloxacin; culture; middle ear effusion; otitis media; otorrhea; tympanostomy tube