ATOMIC Ears: A Phase IIB randomised controlled trial to assess safety, tolerability and acceptability of a 5-day Dornase alfa treatment as an adjunct therapy to ventilation tube insertion for otitis media in children
Telethon Kids Insitute
120 participants
Aug 28, 2020
Interventional
Conditions
Summary
This study will be a Phase IIB trial to look at the safety, tolerability and acceptability of the off-licence use of Dornase alfa into the ear post-ventilation tube insertion ("grommets") in children with chronic otitis media with effusion ("glue ear") and recurrent acute otitis media. We believe that DNA plays a role in maintaining an infectious reservoir in which bacteria can form biofilms and be protected from clearance from the middle ear space. Targeting this DNA scaffolding may improve bacterial clearance from the middle ear and render those bacteria present more susceptible to antimicrobial treatments and the host immune response. From earlier research in our laboratory, we expect that Dornase alfa will help to increase effectiveness of treating middle ear infections and stop new infections from occurring. This would help reduce the number of children who need to have repeat grommet surgeries.
Eligibility
Inclusion Criteria8
- Aged 6 months to less than 5years of age.
- Undergoing surgery for ventilation tube insertion for recurrent acute otitis media or chronic otitis media with effusion, either unilateral or bilateral, which will be performed by a collaborating ear, nose and throat (ENT) surgeon.
- N.B. participants undergoing concurrent adenoidectomy and/or tonsillectomy are permitted to participate.
- Has either a current medically confirmed unilateral or bilateral middle ear effusion that has been present for 3 months or longer and/or had 3 episodes of medically confirmed acute otitis media in the previous 6 months or 4 or more episodes in the previous 12 months.
- Considered to be generally healthy as established by medical history before entering the study, excluding medical conditions listed in inclusion criterion 3.
- N.B. The participant must also not meet exclusion criterion 8.
- Parent/legal guardian has given written informed consent and is willing and able to comply with the scheduled visits and study procedures. This includes access to a telephone for surveillance contacts.
- Is available for the entire study period.
Exclusion Criteria8
- Has a diagnosed sensorineural hearing loss, cystic fibrosis, a craniofacial disorder or immotile cilia syndrome.
- Has a confirmed or suspected immunosuppressive or immunodeficient condition.
- Has a suspected or diagnosed genetic syndrome or chromosomal disorder.
- Has experienced an allergic reaction to protein of Chinese Hamster Ovary origin.
- Has experienced an allergic reaction or has a contra-indication to ciprofloxacin.
- Does not have access to a refrigerator to store the 5 day course of study medication that will be administered to the participant at home by the parent/legal guardian.
- Has received any investigational or non-registered drugs, vaccines or devices within 6 months of study visit 1 (day of surgery) or planned administration during the entire study period.
- Any other significant acute or chronic medical condition that in the opinion of the investigator may interfere with the interpretation of study results or place the participant at increased risk if they participate in the study.
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Interventions
Participants will be randomised 1:1 to Dornase alfa or placebo (normal saline). Administration will be blinded. 1. Pulmozyme® solution containing 1.0 mg/mL recombinant human deoxyribonuclease I (Dornase alfa). The first dose of Dornase alfa will be administered intra-operatively. The participant’s Ear Nose and Throat (ENT) surgeon will administer 0.5mL of Dornase alfa into the participant’s ear/s intra-operatively following ventilation tube (VT) insertion. This may be unilateral if only a single VT is inserted or bilateral if a VT is inserted in both ears. Post-operatively the participant’s parent/legal guardian will administer an additional 10 doses of Dornase alfa. The dosing regimen will be 5 drops twice daily (intra-auricular) for all participants, commencing on the first evening post-Ventilation tube insertion (day 0) until the final dose is administered during the morning of the fifth post-operative day (day 5). A minimum period of 4 hours must be observed between the intra-operative dose of Dornase alfa and the first post-operative dose. The intra-operative dose administered by the participant's ENT surgeon will be documented in the participant's hospital medication record and also documented by the study staff on a centrally maintained master log. To monitor compliance with parental administration of Dornase alfa the clinical trials pharmacist will record the weight of the filled ear dropper bottle when it is dispensed and again when it is returned to pharmacy post-visit 2 (day 14). Parents/legal guardians will also be asked to complete a “study medication administration card” each time they administer the Dornase alfa, which will include the time of each dose. If a dose is missed or is not administered as per the administration instructions (5 drops) this will also be noted by the parent/ legal guardian on the “study medication administration card”. 2. All participants allocated to the Dornase alfa group will also receive Ciloxan (Ciprofloxacin) 0.3% ear drops, as per standard medical practice post-ventilation tube insertion. Parents will be advised to wait at least 10 minutes between administering the Dornase alfa (first) and the ciprofloxacin ear drops (second). Parents/legal guardians will also be asked to complete the “study medication administration card” each time they administer the ciprofloxacin ear drops.
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ACTRN12619001306101