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Original Investigation
September 2018

Dornase Alfa Ototoxic Effects in Animals and Efficacy in the Treatment of Clogged Tympanostomy Tubes in Children: A Preclinical Study and a Randomized Clinical Trial

Author Affiliations
  • 1Department of Otolaryngology–Head and Neck Surgery, University of Colorado School of Medicine, Aurora
  • 2Department of Pediatric Otolaryngology, Children’s Hospital Colorado, Aurora
  • 3Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora
  • 4Loma Linda University School of Medicine, Loma Linda, California
JAMA Otolaryngol Head Neck Surg. 2018;144(9):776-780. doi:10.1001/jamaoto.2018.1101
Key Points

Question  Is it safe and efficacious to use dornase alfa for the treatment of clogged tympanostomy tubes (TTs) in children?

Findings  After establishing that dornase alfa is nonototoxic in a chinchilla model, a randomized clinical trial of 40 children was conducted. At the day-14 visit, the number of unclogged TTs was nonsignificantly higher in the dornase alfa group compared with the ofloxacin group.

Meaning  The pilot clinical trial likely showed safety but failed to show efficacy of dornase alfa to unclog tympanostomy tubes in children.

Abstract

Importance  Many treatments for clogged tympanostomy tubes (TTs) have been proposed, but none have met scientific rigor for safety and efficacy, including the popular empirical use of ototopical antibiotic drops. Dornase alfa, a recombinant molecule with the unique property of cleaving DNA, may be ideal in treating clogged TTs because both middle-ear effusion and the plug are abundant with DNA.

Objective  To investigate the ototoxic effects of dornase alfa in a chinchilla model and its efficacy in a clinical trial in children with clogged TTs.

Design, Setting, and Participants  The safety profiles of dornase alfa (full-strength and 1:10 strength) were evaluated in chinchilla middle ears using serial auditory brainstem response. The efficacy of ototopical dornase alfa (full-strength) was evaluated in children with clogged TTs in a prospective, single-blind randomized clinical trial. The animal study included 21 chinchillas and was conducted at Loma Linda University, Loma Linda, California, and the clinical trial was conducted at Children’s Hospital Colorado, Aurora. A total of 40 children (50 ears with tubes) were enrolled.

Interventions  In the animal study, chinchillas were assigned to 3 groups: controls (saline), full-strength dornase alfa, or 1:10 dornase alfa dilution. Children were randomly assigned to receive either topical dornase alfa or ofloxacin for clogged TT, 5 drops each ear twice a day for 7 days.

Main Outcomes and Measures  Animal study: Auditory brainstem responses. Randomized trial of children participants: The primary outcome was patency of TT at day 14 assessed by otoscopy and tympanometry.

Results  The chinchilla study showed similar auditory brainstem response degradation during a 6-hour period between the control (n = 5) and treatment groups (n = 21). In the clinical trial, a total of 40 clogged TTs (in 33 children, including 25 boys [76%]; mean age, 4.3 years; median [range] age, 3.4 [1.0-14.3] years) were analyzed. The number of unclogged TTs was higher in the dornase alfa group (13 [59%]) compared with the ofloxacin group (8 [44%]), with a difference of 15% (odds ratio, 1.8; 95% CI, 0.54-6.72).

Conclusions and Relevance  The chinchilla model suggests that dornase alfa is likely nonototoxic. The pilot clinical trial failed to show efficacy of dornase alfa to unclog TTs. With the difference seen between the treatment groups, a sample size estimate could be calculated for a future large-scale trial.

Trial Registration  ClinicalTrials.gov identifier: NCT00419380

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