A Phase 4 interventional study of Amoxicillin and Amoxicillin + Clavulanate in Acute Otitis Media and AOM - Acute Otitis Media, sponsored by Kuopio University Hospital. Not yet recruiting at 3 sites in Finland. Open to participants aged 6 Months to 35 Months. Per ClinicalTrials.gov, last updated 2026-10-16.
Sponsored by Kuopio University Hospital · Phase 4, Interventional, and Treatment
The goal of this trial is to compare amoxicillin to amoxicillin-clavulanate and to placebo in the treatment of acute middle ear infections in small children. It will also learn about the possible side effects of antibiotics as compared to placebo.
The main questions it aims to answer are:
Participants will:
Take one of the two antibiotics or a placebo every day for 7 days.
Background Although acute otitis media (AOM) is very common among young children, the evidence concerning its proper treatment is scarce and rather old. Amoxicillin is the most common treatment of AOM in everyday practice. Still, placebo-controlled, high-quality trials on amoxicillin are missing and amoxicillin has not been compared with amoxicillin - clavulanate. We have thus designed a parallel-grouped triple-blinded randomized controlled superiority trial concerning the efficacy of amoxicillin, amoxicillin-clavulanate or placebo in the treatment of AOM. We use commercially available products as study medicines.
Methods The study is a randomized, triple-blind, placebo-controlled clinical trial comparing the efficacy of amoxicillin with placebo and amoxicillin-clavulanic acid in the treatment of acute otitis media in children. Patients, children 6-35 months of age with the diagnosis of AOM and passing predefined inclusion and exclusion criteria, will be recruited from primary care. Three research centers are recruiting: Mikkeli, Kuopio and Turku.
The aims of this project are to find out:
1) Is amoxicillin superior to placebo in treatment of childhood acute otitis media? 2) Is amoxicillin clavulanic acid superior to amoxicillin in treatment of childhood acute otitis media? 3) What is the effect of antibiotic treatments, either with amoxicillin or amoxicillin-clavulanate in comparison to placebo, on the recovery of AOM in relation to the harms? 4) What is the effect of different risk factors (e.g. age, history of otitis, exposure to tobacco smoke, lack of breastfeeding, use of a pacifier, unilateral/bilateral episode) on the recovery of AOM? 5) Is there a difference in the course of AOM in different viral upper respiratory tract infections? 6) What is the impact of nasopharyngeal carriage of otopathogenic bacteria on the course of AOM? 7) What is the effect of antimicrobial treatment of AOM on the carriage of nasopharyngeal bacteria compared to placebo? The primary outcome in this trial are the symptoms of the child having AOM, measured with the newly validated AOM SOS symptom score 6.0. The primary analyses will be performed with generalized estimation equations (GEE) as proposed by the developing team of AOM-SOS v6.0. Secondary and other outcomes are collected along newly reported Core Outcome Set for AOM. To avoid type 1 error, secondary outcomes are analyzed with serial gatekeeping strategy.
To follow the needs for research on antimicrobial treatment, we have planned to perform, in addition to traditional intention to treat and per protocol analyses, also DOOR (Desirability of Outcome Ranking) -analyses. These analyses help to appraise the benefit/harm -balance of various treatments.
For sample size calculations the mean SD of the AOM-SOS v6.0 is supposed to be 12 points and the mean clinically important difference (MID) 5 points. With an assumed loss of 10%, altogether 219 children will be recruited.
All patients will be randomized to receive one of the following treatments per orally:
Amoxicillin
- The dose of amoxicillin is 40-50 mg/kg/day divided into two daily doses for 7 days
Amoxicillin-clavulanate
- The dose is as amoxicillin 40-50mg/kg/day divided into two daily doses for 7 days
Placebo
A polyester fiber swab sample is taken from the nasopharynx of all children to detect respiratory viruses and bacteria both at recruitment and at 7-9 day visit (Multiplex-PCR).
Study clinic visits continue weekly until symptoms, inflammatory changes in the tympanic membrane, middle ear effusion and/or tympanometry have normalized. In case of prolonged effusion (>3 months), the child is referred to an otolaryngologist.
Impact The trial will produce important and highly needed knowledge for the treatment of the most common pediatric infectious disease, where antimicrobial treatment is used. The project will result in three doctoral dissertations and several other publications. In addition, a large amount of material will be generated for further research.
288 studies on the registry are indexed under Otitis Media; 35 are open to participants now.
This study's planned enrollment of 219 is above the median of 135 across 197 interventional studies indexed under Otitis Media.
Browse Otitis Media studies →Kuopio University Hospital is the lead sponsor of 135 studies on the registry; 24 are open to participants now.
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acute otitis media along the diagnostic criteria:
Exclusion Criteria:
complicated AOM
Amoxicillin-clavulanate 40mg/kg/day as amoxicillin divided to two daily doses for 7 days
Drug: Amoxicillin + Clavulanate
Placebo (Syrspend) administered twice daily for seven days
Drug: Placebo
Amoxicillin 40mg/kg/day divided to two doses (the usual dosage in Scandinavia) for 7 days
Drug: Amoxicillin
Amoxicillin administered twice daily for seven days
Drug pages: Amoxicillin · Clavulanic Acid
Amoxicillin-clavunate administered twice daily for seven days
Placebo administered twice daily for seven days
Symptoms of the child
Daily AOM-SOS score version 6.0. measured by the parents. The treatment effectiveness measured as risk ratios and generalized estimation equations (GEE) are used to convert the daily mean comparisons into relative effect estimates.
Time frame: From enrollment to the day 14 of the follow-up
Time to treatment failure
Treatment failure is a composite endpoint, consisting of six independent components: 1. no improvement in overall condition by the first scheduled visit (day 2-4) (i.e., unless parents thought that their child's overall condition was improving, the case was categorized as treatment failure), 2. a worsening of the child's overall condition at any time, 3. no improvement in otoscopic signs by the end-of treatment visit on day 7-9, 4. perforation of the tympanic membrane or severe infection (e.g., mastoiditis or pneumonia) at any time 5. necessitating systemic open-label antimicrobial treatment at any time, 6. any other reason for stopping the study drug (e.g., an adverse event or nonadherence to the study drug) at any time.
Time frame: From enrollment to the day 10 of the follow-up
The duration of middle ear effusion
The duration of middle ear effusion is measured with video-otoscopy and tympanometry at physician visits
Time frame: From enrollment until the ear is cured and effusion vanished. If effusion persist for 3 months, the follow up is discontinued and the child is referred to ENT specialist.
The mean number of pain medication doses
The parents give the amount of pain medication doses daily by MyCap (REDCap) system
Time frame: From enrollment to day 7 of the follow up
The mean AOM-SOS score value
The mean AOM-SOS score values in each group
Time frame: the first 7 days after randomization
Contralateral AOM
The proportions of children with development of contralateral AOM during the treatment
Time frame: the first 7 days after randomization
Side effects
The proportions of children with side effects (for ex. diarrhea, rash)
Time frame: the first 7 days after randomization
AOM recurrences
The mean number of AOM recurrences after the trial in the next 12 months, data collected from patient records, Kanta
Time frame: 12 months from enrollment
Missed days from day care and work
The mean number of missed days from day care (participants) and work (parents) during the first 7 days after randomization
Time frame: The first 7 days after randomization
Nasopharyngeal colonization of otopathogens and the composition and function of nasopharyngeal microbiome
The proportion of children with nasopharyngeal colonization of otopathogens and the composition and function of nasopharyngeal microbiome before and after the treatment
Time frame: The first 7 days after randomization
The effect of nasopharyngeal viruses in the course of AOM
The proportions of children with no improvement of overall condition by the first scheduled control visit (day 2-4), with no improvement of otoscopic signs (7-9 day visit) and with middle ear effusion at days 2, 7 and 14) along viral findings in the nasopharyngeal samples
Time frame: The first 14 days after randomization
Need of rescue antibiotics
The proportions of children needing rescue antibiotics, with spontaneous perforation and with middle ear effusion at days 2, 7 and 14 along nasopharyngeal otopathogen findings
Time frame: The first 14 days after randomization
Risk factors
The effect of risk factors (age, history of otitis, exposure to tobacco smoke, lack of breastfeeding, use of a pacifier, daycare, unilateral/bilateral episode) on the course of AOM
Time frame: The first 14 days after randomization
Plan to share: No
No publications or documents are linked to this record.
Start is estimated for Nov 2026; primary completion for Dec 2029, 37 months later.
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From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drugs tested here: Amoxicillin · Clavulanic Acid