Investigators: Chris Brennan-Jones, Glenn Pearson, Harvey Coates, Jafri Kuthubutheen, Lea-Ann Kirkham, Peter Richmond, Ruth Thornton, Shyan Vijayasekaran
External collaborators:Chady Sader (Western ENT), Shane Ling (Western ENT), Timothy Cooney (Perth ENT Centre), Hayley Herbert (Perth Children's Hospital), Anton Hinton-Barye (ENT Private Practice), Darin Bilish (Perth ENT), Desmond Wee (Western ENT), Fiona Whelan (Western ENT), Alastair MacKendrick (Western ENT), Jess Chong (Western ENT)
Summary: The thick glue filling the middle ears of children with ear infection is largely made up of DNA from the children's own immune response and the bacteria live in this, protected from antibiotics. Many children need grommets to fix the hearing loss associated with this glue however up to 1/3 of children need repeat operations. This study aims to whether a treatment known as Dornase alfa used at the time of grommet insertion breaks up this DNA and decreases the need for repeat sets of grommets.
Project description:
Middle ear infection (otitis media, OM) is the most common reason for a child to visit their doctor and be prescribed antibiotics. With a global estimate of 709 million cases of acute OM and 21,000 deaths due to OM complications each year, treatments to reduce the burden of OM will have a significant impact on childhood morbidity and mortality. Increases in the rate of children suffering from recurrent OM have been observed globally, and antibiotic treatment is often ineffective at providing long term resolution. We have shown that the bacteria that cause OM can survive in biofilms within the middle ear and evade antibiotics, contributing to the persistence and recurrence of infection. We have also shown that these biofilms exist within DNA derived from the children’s own immune response. This DNA increases the viscosity of the middle ear fluid giving it the tenacious consistency known as “glue” ear.
Dornase alfa (Da) is a recombinant human deoxyribonuclease that cleaves extracellular DNA, and is used to reduce sputum viscosity in lungs of patients with cystic fibrosis to facilitate bacterial clearance by antibiotics. We have shown that Da can dissolve the glue-like DNA in middle ear fluid from children with chronic OM. We recently conducted a Department of Health funded pilot study of to test the safety and efficacy of Da treatment on 60 children with bilateral OM undergoing their first ventilation tube insertion (grommets). Children were administered Da into one ear and saline into the other ear at the time of grommet insertion, and were then treated with topical antibiotics and followed for 2 years. Da treatment at the time of surgery was safe and increased time until ventilation tube blockage or extrusion. Based on these data, we propose a Phase IIB randomised controlled trial to assess safety and efficacy of using Da at the time of surgery and for 5 days post-operatively in reducing repeat grommet surgery for children with chronic and recurrent OM.