To establish the clinical and cost-effectiveness of antibiotic-corticosteroid eardrops as compared with oral antibiotics in children with AOMd.
ID
Source
Brief title
Condition
- Middle ear disorders (excl congenital)
- Hepatobiliary neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is the proportion of children without ear pain and fever at
day 3.
Secondary outcome
Secondary outcomes are ear pain intensity/severity; fever intensity/severity;
ear discharge; time to resolution of total symptoms, persistent eardrum
perforation; middle ear effusion; adverse events; disease-specific quality of
life; antibiotic consumption; AOM recurrences; costs and cost-effectiveness;
antimicrobial resistance.
Background summary
Around 15-20% of children with AOM present with ear discharge due to a
spontaneous perforation of the eardrum (AOMd). Since oral antibiotics
effectively reduce ear pain and/or fever in children with AOMd, current
guidance recommends general practitioners (GPs) to consider oral antibiotics
for these children. However, oral antibiotics put children at risk for side
effects and increase the risk of antimicrobial resistance. In children with
AOMd, the perforation of the eardrum provides an opportunity to instill topical
antibiotics directly into the middle ear without exposing children to systemic
side effects and putting less selective resistance pressure on bacteria.
Evidence on its effectiveness in children with AOMd is, however, lacking. We
hypothesise that antibiotic-corticosteroid eardrops are non-inferior to oral
antibiotics in resolving ear pain and fever at day 3 (72 hours after
randomisation) in children aged 6 months to 12 years visiting their GP with
AOMd and ear pain and/or fever.
Study objective
To establish the clinical and cost-effectiveness of antibiotic-corticosteroid
eardrops as compared with oral antibiotics in children with AOMd.
Study design
A primary care based, open, randomised controlled non-inferiority trial.
Intervention
Children will be randomly allocated to either 1)
hydrocortisone-bacitracin-colistin (Bacicoline-B®) eardrops, five drops, three
times per day in the discharging ear(s) for 7 days or 2) amoxicillin suspension
or tablets 50 mg per kilogram body weight per day, divided over three oral
doses for 7 days.
Study burden and risks
Participants will be followed for a total of 3 months. This includes a baseline
visit, a telephone call at day 3 and a follow-up visit at 2 weeks. Parents of
participating children will be asked to record their child*s symptoms in a
daily diary during the first 2 weeks and a weekly diary afterwards (up to 3
months). At the baseline and the 2 weeks home visits, otoscopy will be
performed and otorrhoeal, nasopharyngeal and faecal samples will be collected.
At the 2 weeks home visit tympanometry will be performed and at 3 months, a
faecal sample will be collected.
Children allocated to eardrops will not be exposed to systemic side effects
associated with oral antibiotics and may be at lower risk of developing
antimicrobial resistance. A potential risk is that children may experience a
prolonged disease course and might need subsequent treatment with oral
antibiotics if antibiotic-corticosteroid eardrops appear to be inferior to oral
antibiotics. We however do not anticipate large differences in treatment
failures between the two active treatment groups given the difference (30%)
observed between oral antibiotics and placebo in previous trials.
The main risk of eardrops is potential ototoxicity. Although the
hydrocortisone-bacitracin-colistin eardrops do not contain an aminoglycoside,
there still is a risk. However, based on current available literature and
recent data from the Netherlands Pharmacovigilance Centre, the risk of
ototoxicity associated with the use of eardrops is considered at most similar
but probably lower than the risk of ototoxicity related to the middle ear
infection itself. Both the Dutch College of General Practitioners and the Dutch
ENT Society have balanced benefits and risks of using these eardrops in
children with an active middle ear infection and concluded that the (potential)
benefits outweigh the risks.
Based on these considerations, we regard the proposed study as a low risk
study.
Heidelberglaan 100
Utrecht 3584CX
NL
Heidelberglaan 100
Utrecht 3584CX
NL
Listed location countries
Age
Inclusion criteria
Children aged 6 months to 12 years whose parents are consulting the GP with AOM
and ear discharge in one or both ears (<= 7 days duration) and either
parent-reported ear pain in the previous 24 hours or fever (child*s body
temperature of >= 38.0°C in the previous 24 hours as reported by parents or as
measured by the GP during consultation) or both.
Exclusion criteria
Children will be excluded from participation if they
1. are systemically very unwell and requires immediate oral antibiotics or
immediate hospitalization (e.g. child has signs and symptoms of serious illness
and/or complications such as mastoiditis/meningitis);
2. are at high risk of serious complications including children with known
immunodeficiency other than partial IgA or IgG2 deficiencies, craniofacial
malformation such as cleft palate, children with Down syndrome, previous ear
surgery other than grommet insertion;
3. have grommets in place;
4. have a pre-existing perforation of the eardrum;
5. had an prior AOM episode (with or without ear discharge) in previous 28 days;
6. used oral antibiotics or topical antibiotics in previous 2 weeks;
7. have a known allergy or sensitivity to oral amoxicillin or
hydrocortisone-bacitracin-colistin;
8. have already participated in this trial.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-000332-34-NL |
| CCMO | NL61395.041.17 |
| OMON | NL-OMON23467 |