Analgesic Ear Drops for Children With Acute Otitis Media

Study Overview
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Brief Summary
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This trial aims to investigate whether analgesic ear drops added to usual care provide superior ear pain relief over usual care alone in children presenting to primary care with AOM. Children will be randomly allocated (ratio 1:1) to either 1) lidocaine hydrochloride 5mg/g ear drops (Otalgan) 1-2 drops up to six times daily for a maximum of 7 days in addition to usual care (oral analgesics, with/without antibiotics) or 2) usual care. Parents will complete a symptom diary for 4 weeks as well as generic and disease-specific quality of life questionnaires at baseline and 4 weeks. The primary outcome is the parent-reported ear pain score (0-10) over the first 3 days. NOTE: At the time of publication of the study protocol paper, the investigators were unable to make any amendments to the trial registration record in the Netherlands Trial Register (NTR) (NL9500; date of registration: 28 May 2021). The addition of a data sharing plan was required to adhere to the International Committee of Medical Journal Editors (ICMJE) guidelines. The investigators therefore re-registered the trial in ClinicalTrials.gov. This second registration is for modification purposes only and the NTR record (NL9500) should be regarded as the primary trial registration.

Official Title
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Effectiveness of Analgesic Ear Drops as add-on Treatment to Oral Analgesics in Children With Acute Otitis Media: a Pragmatic Randomised Controlled Trial

Conditions
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Acute Otitis Media, Pain

Intervention / Treatment
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* Drug: lidocaine hydrochloride 5mg/g


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 1 to 6 years Parent-reported ear pain in 24 hours prior to enrolment GP-diagnosis of (uni- or bilateral) AOM Exclusion Criteria: with (suspected) tympanic membrane perforation or ventilation tubes with ear wax obscuring visualisation of the tympanic membrane who are systemically very unwell or require hospital admission (e.g. child has signs and symptoms of serious illness and/or complications such as mastoiditis/meningitis) who are at high risk of serious complications including children with known immunodeficiency other than partial IgA or IgG2 deficiencies, craniofacial malformation including cleft palate, Down syndrome and previous ear surgery (with the exception of ventilation tubes in the past) who have a known allergy or sensitivity to study medication or similar substances (e.g. other amide-type anaesthetics: bupivacaine, mepivacaine, prilocaine, etc) who have taken part in any research involving medicines within the last 90 days, or any other AOM-related research within the last 30 days who suffer from chronic recurrent pain of another origin than the ear who have participated in this trial during prior AOM episode

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: pragmatic, two arm, individually randomised, open, superiority trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lidocaine ear drops with usual care<br>usual care: oral analgesic with/without antibiotics | Drug: lidocaine hydrochloride 5mg/g<br>* 1-2 drops up to six times daily for a maximum of 7 days<br>* Other names: Otalgan;|
| No Intervention: usual care<br>usual care: oral analgesic with/without antibiotics | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The parent-reported ear pain score over the first three days | Parents will record their child's ear pain scores during the first three consecutive days using a 0-10 validated numerical rating scale. Higher scores indicate greater severity. | 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of children consuming antibiotics |  | in the first 7 days | 
| proportion of children with oral analgesic use |  | in the first 7 days | 
| overall symptom burden (crying/distress, disturbed sleep, interference with normal activity, appetite, fever and hearing problems) using a 0-6 Likert scale | higher scores indicate greater severity | in the first 7 days | 
| number of days with ear pain |  | during follow up (4 weeks) | 
| number of GP reconsultations with/without subsequent antibiotic prescribing |  | during follow-up (4 weeks) | 
| number of participants with adverse events |  | during follow-up (4 weeks) | 
| number of participants with complications of AOM |  | during follow-up (4 weeks) | 
| costs | Mean costs per patient will be compared across the randomisation groups | during follow-up (4 weeks) | 
| generic quality of life of the child assessed using the 47-item short-form of the Infant Toddler Quality of Life Questionnaire (ITQOL-SF47) | The questionnaire consists of 47 items in the following areas: overall health, physical abilities, growth and development, pain, temperament and moods, behavior, general health, parental emotional impact, parental time impact, and family cohesion. Scale for each area: from 0 (worst health) to 100 (best health) | at baseline and at 4 weeks | 
| disease-specific quality of life of the child assessed using the Otitis media-6 (OM-6) questionnaire | The 6 questions measure Physical Suffering, Hearing Loss, Speech Impairment, Emotional Distress, Activity Limitations, and Caregiver Concerns. Responses for each item were scored from 1 to 7 (1=Not present/no problem; 2=Hardly a problem at all; 3=Somewhat of a problem; 4=Moderate problem; 5=Quite a bit of a problem; 6=Very much of a problem; 7=Extreme problem). A mean score of all six items comprises the OM Total Score. Higher mean scores of all six items indicate greater severity and impact of OM on the child's QOL. | at baseline and at 4 weeks | 
| incremental cost-effectiveness ratios; calculated by dividing the estimated differences in costs between groups by the differences in effects observed | i.e. the additional cost per additional 1 point reduction in mean ear pain score over the first three days for the analgesic ear drops group versus the usual care group | during follow-up (4 weeks) |