Analgesic Ear Drops for Children With Acute Otitis Media (OPTIMA)

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

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.

Study Overview

• Status: Terminated
• Conditions: Pain; Acute Otitis Media
• Intervention / Treatment: Drug: lidocaine hydrochloride 5mg/g

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • University Medical Center Utrecht

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 4 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Investigators: Principal Investigator: Roderick Venekamp, UMC Utrecht

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2021
• Primary Completion (Actual): December 16, 2023
• Study Completion (Actual): January 10, 2024

Study Registration Dates

• First Submitted: November 9, 2022
• First Submitted That Met QC Criteria: December 6, 2022
• First Posted (Actual): December 15, 2022

Study Record Updates

• Last Update Posted (Estimated): May 13, 2024
• Last Update Submitted That Met QC Criteria: May 9, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Otorhinolaryngologic Diseases; Ear Diseases; Otitis; Otitis Media; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lidocaine
• Other Study ID Numbers: 80-87200-98-1017; NL9500 (Registry Identifier: Netherlands Trial Register); 10060011910003 (Other Grant/Funding Number: The Netherlands Organisation for Health Research and Development (ZonMw)); 2021-003019-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: On completion of the trial, data will be stored for a minimum of 25 years at a central data drive at the Julius Center. The investigators will publish the metadata in the DataverseNL repository and will provide a persistent identifier. The data will be available to researchers who provide a methodologicaly sound proposal to achieve the aims in the approved proposal. Proposals to gain access to the data should be directed to the principle investigator (RPV). Data requestors will need to sign a data sharing agreement.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No