title: Efficacy and Safety of Ciprofloxacin Plus Fluocinolone in Otitis Media With Tympanostomy Tubes in Pediatric Patients: A Randomized Clinical Trial.
abstract: Acute otitis media with tympanostomy tubes (AOMT) in children commonly presents with otorrhea and negatively affects their daily activities.
  
  
  
  To evaluate the efficacy and safety of topical ciprofloxacin, 0.3%, plus fluocinolone acetonide, 0.025%, otic solution relative to ciprofloxacin, 0.3%, otic solution alone and fluocinolone acetonide, 0.025%, otic solution alone in the treatment of AOMT in children.
  
  
  
  Two twin multicenter, randomized, double-blind clinical trials with identical designs were conducted from June 24, 2011, through June 23, 2014, at ear, nose, and throat pediatric practices, general practices, hospitals, and clinical research centers. The study population comprised 662 children (331 in each trial) with AOMT in at least 1 ear who presented with moderate or severe purulent otorrhea for 3 weeks or less. Data analyses were performed on an intention-to-treat basis.
  
  
  
  Patients were randomly assigned to receive ciprofloxacin plus fluocinolone, ciprofloxacin alone, or fluocinolone alone twice daily for 7 days and were evaluated on days 1 (baseline), 3 to 5 (undergoing therapy), 8 to 10 (end of therapy), and 18 to 22 (test of cure).
  
  
  
  The primary efficacy measure was time to cessation of otorrhea. The principal secondary end point was sustained microbiological cure, defined as eradication or presumed eradication at end-of-therapy and test-of-cure visits.
  
  
  
  A total of 662 children participating in the 2 studies were randomized to receive ciprofloxacin plus fluocinolone (n = 223), ciprofloxacin alone (n = 221), or fluocinolone alone (n = 218). The median age was 2.5 years (range, 0.6-12.7 years). The median time to cessation of otorrhea was 4.23 days (95% CI, 3.65-4.95 days) in patients receiving ciprofloxacin plus fluocinolone compared with 6.95 days (95% CI, 5.66-8.20 days) in those receiving ciprofloxacin and not estimable findings in those receiving fluocinolone alone (P < .001). The clinical cure rate at the test-of-cure visit was 80.6% in the ciprofloxacin plus fluocinolone group, 67.4% in the ciprofloxacin group (difference, 13.2%; 95% CI, 5.0%-21.4%; P = .002), and 47.6% in the fluocinolone group (difference, 33.0%; 95% CI, 24.0%-42.0%; P < .001). The sustained microbiological cure rate was 79.7% in the ciprofloxacin plus fluocinolone group vs 67.7% in the ciprofloxacin group (difference, 12.0%; 95% CI, 0.8%-23.0%; P = .04) and 37.6% in the fluocinolone group (difference, 42.1%; 95% CI, 29.3%-54.8%; P < .001). Only 7 (3.1%) of the patients receiving ciprofloxacin plus fluocinolone, 8 (3.6%) of the patients receiving ciprofloxacin, and 10 (4.7%) of the patients receiving fluocinolone presented with adverse events related to study medication.
  
  
  
  The combination of ciprofloxacin plus fluocinolone is more effective than treatment with ciprofloxacin or fluocinolone alone for AOMT, and it is safe and well tolerated in children.
  
  
  
  clinicaltrials.gov Identifiers: NCT01395966 and NCT01404611.
authors.affiliation: Center for Pediatric ENT-Head and Neck Surgery, Boynton Beach, Florida.
authors.forename: Zorik
authors.initials: Z
authors.lastname: Spektor
authors.affiliation: Otolaryngology Department, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: Felix
authors.initials: F
authors.lastname: Pumarola
authors.affiliation: private practice, Johannesburg, South Africa.
authors.forename: Khaleed
authors.initials: K
authors.lastname: Ismail
authors.affiliation: Central California Clinical Research, Fresno.
authors.forename: Brent
authors.initials: B
authors.lastname: Lanier
authors.affiliation: Vital Prospects Clinical Research Institute PC, Tulsa, Oklahoma.
authors.forename: Iftikhar
authors.initials: I
authors.lastname: Hussain
authors.affiliation: Carolina ENT Clinic (Centri Inc), Orangeburg, South Carolina.
authors.forename: John
authors.initials: J
authors.lastname: Ansley
authors.affiliation: Spartanburg Ear Nose & Throat, North Grove Medical Park, Spartanburg, South Carolina.
authors.forename: Henry F
authors.initials: HF
authors.lastname: Butehorn
authors.affiliation: Ear, Nose, and Throat, Constantiaberg Medi-Clinic, Cape Town, South Africa.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Esterhuizen
authors.affiliation: Greensboro Ear, Nose & Throat, Greensboro, North Carolina.
authors.forename: John
authors.initials: J
authors.lastname: Byers
authors.affiliation: private practice, Conroe, Texas.
authors.forename: Franklin
authors.initials: F
authors.lastname: Douglis
authors.affiliation: Ear, Nose, and Throat Department, NEA Baptist Clinic, Jonesboro, Arkansas.
authors.forename: Bryan
authors.initials: B
authors.lastname: Lansford
authors.affiliation: Otolaryngology Department, Hospital Quirón, Madrid, Spain.
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Hernández
mesh_terms: D000208:Acute Disease; D000287:Administration, Topical; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002939:Ciprofloxacin / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005446:Fluocinolone Acetonide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D008297:Male; D008876:Middle Ear Ventilation; D010033:Otitis Media / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D005446:Fluocinolone Acetonide; D002939:Ciprofloxacin; C035394:fluocinolone