|- candidate number||27956|
|- NTR Number||NTR6723|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||27-sep-2017|
|- Secondary IDs||EudraCT number: 2017-000332-34 ABR number: 61395|
|- Public Title||Is treatment with eardrops as good as oral treatment for children with acute otitis media presenting with ear discharge?|
|- Scientific Title||Topical or oral antibiotics for children with acute otitis media presenting with ear discharge?
|- ACRONYM||PLOTS (Pijnlijk LoopOor Therapie Studie)|
|- hypothesis||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 either ear pain or fever or both.|
|- Healt Condition(s) or Problem(s) studied||Otorrhea, Otitis media|
|- 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 hospitalisation (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 a 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.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-nov-2017|
|- planned closingdate||1-nov-2019|
|- Target number of participants||350|
|- Interventions||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.|
|- Primary outcome||The proportion of children without ear pain (ear pain score 0 on the 0-6 Likert scale) and fever (body temperature below 38.0°C) 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.|
|- Timepoints||Primary outcome: day 3|
Secondary outcomes: 0-3 days, 2 weeks, 3 months
|- Trial web site||www.plots-studie.nl|
|- CONTACT FOR PUBLIC QUERIES||Drs. Saskia Hullegie|
|- CONTACT for SCIENTIFIC QUERIES||Drs. Saskia Hullegie|
|- Sponsor/Initiator |
(Source(s) of Monetary or Material Support)
|ZonMw, Rational Pharmacotherapy 5th Open Call – grant no. 84801 5006|
|- Brief summary||Rationale: 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 adverse 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 either ear pain or fever or both.|
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.
Study population: Children aged 6 months to 12 years whose parents are consulting their GP because of AOMd and either ear pain or fever or both.
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.
Main study parameters/endpoints: The primary outcome is the proportion of children without ear pain and fever at day 3. 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.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
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. At the baseline and the 2 weeks home visits, otoscopy and tympanometry (at 2 weeks only) will be performed and otorrhoeal, nasopharyngeal and faecal samples will be collected. At 3 months, a faecal sample will be collected. Data collection methods and associated burden to participants have been extensively discussed with our parent panel. The proposed methods were judged both feasible and acceptable by our parent panel and have been successfully applied in our previous trial.
Children allocated to eardrops will not be exposed to systemic adverse 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 or no treatment 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.
|- Main changes (audit trail)|
|- RECORD||27-sep-2017 - 17-nov-2017|