Oral prednisolone for acute middle ear infection in children

• Register: ANZCTR
• Last refreshed on: 26 August 2019
• Main ID: ACTRN12618000049279
• Date of registration: 16/01/2018
• Prospective Registration: Yes
• Primary sponsor: Respati Wulansari Ranakusuma
• Public title: Oral prednisolone for acute middle ear infection in children
• Scientific title: Oral prednisolone for acute otitis media in children: a pilot pragmatic, randomised, open-label, single-blind study to evaluate feasibility
• Date of first enrolment: 08/03/2018
• Target sample size: 60
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12618000049279.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Blinded (masking used);Assignment: Parallel;Type of endpoint: Efficacy;
• Phase: Phase 3

Countries of recruitment

Indonesia

Contacts

• Name: Dr Respati Wulansari Ranakusuma

• Name: Dr Respati Wulansari Ranakusuma

Key inclusion & exclusion criteria

Inclusion criteria: Children with acute otitis media, defined as a current onset within 48 to 72 hours of ear-related symptoms (e.g. ear pain, ear tugging/rubbing or irritability for non-verbal young children) and/or signs of acute inflammation (e.g. erythema ear drum) and middle ear effusion (e.g. bulding ear drum, air-fluid level, purulent appearance of ear drum) if feasible to assess using otoscope,
Exclusion criteria: 1. Children with major and severe medical conditions (e.g. heart failure, kidney failure)
2. Immunocompromised children (e.g. HIV, children receiving cancer treatment)
3. Children with congenital malformations and/or syndromes (e.g. cleft palate, Down’s syndrome)
4. Children with high risk of risk of strongyloidiasis infection
5. Children with ear ventilation tube(s)
6. Children who had exposed to persons with varicella (chicken pox) or active Zoster infection in the past 3 weeks without any prior varicella immunisation or infection
7. Children who have taken systemic (i.e. oral, injection) or topical steroids in the preceding four weeks
8. Children who have taken antibiotics in the preceding two weeks
9. Children who are hypersensitive to prednisolone or prednisone, or other corticosteroids.

Age minimum: 6 Months
Age maximum: 12 Years
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Ear - Other ear disorders

Acute otitis media in children;
Acute otitis media in children

Infection - Other infectious diseases

Intervention(s)

Oral prednisolone (tablet):
- The dose administered based on age range: once daily of 10 mg for children aged 6 months to < 2 years; 20 mg for children aged 2 years to < 6 years; and 30 mg for children aged 6 years to 12 years
- The duration of administration: 5 (five) days
- The mode of administration: oral tablet
Prednisolone tablets will be crushed by the pharmacist, then will be mixed with sweeteners, and packed in a daily-dose paper-wrap.
Children will be stratified based on disease severity to mild or severe acute otitis media (AOM).
Children with mild symptoms and signs of AOM (e.g. mild ear pain fever less than 39 degree Celcius, mild bulging of ear drum) will be randomly allocated to intervention group (will receive oral prednisolone plus 48-hour expectant observation) or control group (48-hour expectant observation alone).
Children with severe symptoms and signs of AOM (e.g. moderate to severe ear pain, fever 39 degree Celsius or more, moderate-to-severe bulging of the ear drum, AOM complications) will be randomly allocated to intervention group (will receive oral prednisolone plus antibiotics based on physicians' preferences) or control group (antibiotics alone).
Parents or the caregivers will give the study medication to their children at home, once daily, in the morning (before 9 am) after breakfast, with a glass of water, milk, or juice, or mix the study medication powder with a small amount of soft food such as jam and yoghurt. to make the taste more palatable for children.
Research team will send a daily text message to remind the parents/caregivers to give the study medicine daily for five days. We will also provide a symptom diary (consists of three mini booklets of diary that will record the symptoms at: (1) Day-1 to Day-3 (research team will collect the first booklet at Visit-1 or Day-3 after the randomisation/baseline visit); (2) Day-4 to Day-7 ( will be collected at Visit-2 or Day-7 after the randomisation); an

Primary Outcome(s)

Recruitment rates. It is defined as recruitment rates that will be assessed monthly[We will assess this outcome at each month for the overall 6-month recruitment duration of the pilot study.]

Ability to measure planned outcomes in the main study. We will identify the ability and challenges in measuring planned outcomes in the main study, as follows: (1) the proportion of children with pain reduced by at least the minimum clinically important reduction, at Day-3 after randomisation; (2) the severity of pain and other AOM-relevant symptoms at various time points using visual analogue scale (VAS) and acute otitis media severity of symptoms scale (AOM-SOS); (3) duration to AOM resolution; (4) adverse effects; (5) complication of AOM (e.g. perforation of tympanic membrane, mastoiditis); (6) AOM recurrence, defined as a new episode of AOM at one to three months after randomisation; and (7) the change of middle ear effusion at various time points, including the duration and its correlation with ear pain and other symptoms (i.e. ear tugging, irritability, crying, lack of sleep, lack of appetite, less of playfulness, fever). We will use a questionnaire as a feedback form for physicians, audiologists, nurses, pharmacists, and the parents. The questionnaire consists of questions regarding the experience and challenges they encounter when measuring the outcomes (e.g. recruiting the children, conducting otoscopic and tympanometry examination, completing the case report forms, completing the symptom diary, preparing and dispensing the study medication), We will read the questions along with several options for answers from the feedback form and tick the answers accordingly. If their answers are not available on the form or they have other opinions, then we will write their answers on the 'others' column.
In assessing the symptoms of AOM, we will use validated scales, such as VAS and AOM-SOS. We have translated the English version of AOM-SOS into the Indonesian version through forward and backward translation process. We have designed the other questions in the 'Outcome form' (e.g. questions of the complication of AOM, side effects, the management for the side effects) and the questionnaire in the 'Feedback form' specifically for this study. [At the baseline visit (Visit-0), Day-3 (Visit-1), Day-7 (Visit-2), Day-30 (Visit-3), and Day-90 (Visit-4).
]

The success of the study procedures. We will assess this outcome by identifying the process and obstacles during the following procedures: (1) obtaining informed consents from the patients and their parents; (2) the recruitment using prespecified eligibility criteria and the use of otoscope to confirm AOM if feasible; (3) the stratification and randomisation, including accessing the randomisation number and dispensing the study medication; and (4) the identification of AOM symptoms and signs by clinical history taking and examination using otoscope and tympanometry.[At the baseline visit (Visit-0), Day-3 (Visit-1), Day-7 (Visit-2), Day-30 (Visit-3), and Day-90 (Visit-4).]

Secondary Outcome(s)

The mechanistic sub-study using tympanometry:
Primary outcome - The change of middle ear effusion. We will measure MEE using static acoustic admittance, defined as “the amount of energy absorbed by the tympanic membrane and middle ear, measured in mmho or mL”.
This sub-study will include all children in the pilot study (n=60), as we did not determine a sample size for the pilot study. The sample size of the mechanistic sub-study was determined based on the main primary outcome, which is the mean value of static acoustic admittance or acoustic compliance in the tympanogram. In a previous study of children with middle ear effusion (MEE) who underwent tympanometry assessment and had a history of chronic or recurrent middle ear disease, the response within each subject group was normally distributed with standard deviation 0.3. If the true difference in the experimental and control means is 0.3 units, we will need to study 22 experimental subjects and 22 control subjects to be able to reject the null hypothesis that the population means of the experimental and control groups are equal with probability (power) 0.9. The Type I error probability associated with this test of this null hypothesis is 0.05. With a 20% allowance for dropouts, the total sample size becomes 56 or we will include 60 children for this pilot study. [At the baseline visit (Visit-0), Day-3 (Visit-1), Day-7 (Visit-2), Day-30 (Visit-3), and Day-90 (Visit-4).]

The mechanistic sub-study using tympanometry:
Secondary outcome - The duration of middle ear effusion.
The duration of middle ear effusion is defined as a duration of middle ear effusion represented by the normalisation of the value of static acoustic admittance.
This sub-study will include all children in the pilot study (n=60).[At the baseline visit (Visit-0), Day-3 (Visit-1), Day-7 (Visit-2), Day-30 (Visit-3), and Day-90 (Visit-4).]

Compliance to study visits and study medication. The compliance to study visits and study medication is defined as a proportion of children who regularly take the study medication according to the prespecified dose and duration (assessed using the symptom diary and the number of any left-over drug) and who come to follow-up visits per protocol. Participants will be followed closely by clinicians and research staff. Children will return for a visit at Day-3 after randomisation (Visit-1), ensuring collection of the primary outcome. [At the baseline visit (Visit-0), Day-3 (Visit-1), Day-7 (Visit-2), Day-30 (Visit-3), and Day-90 (Visit-4).]

The mechanistic sub-study using tympanometry:
Secondary outcome - The correlation between ear pain and other symptoms (i.e. ear tugging, irritability, crying, lack of sleep, lack of appetite, less of playfulness, fever) with the changes of middle ear effusion at various time points. At each time point, we will assess the correlation between the value of static acoustic admittance with the severity of ear pain (assessed using VAS) and other non-specific AOM symptoms (assessed using AOM-SOS).
This sub-study will include all children in the pilot study (n=60).[At the baseline visit (Visit-0), Day-3 (Visit-1), Day-7 (Visit-2), Day-30 (Visit-3), and Day-90 (Visit-4).]

Secondary ID(s)

Nil known

Source(s) of Monetary Support

Advance Queensland, Australia (Women’s Academic Fund Maternity funding WAF-7026811-298)

The Australian Government Research Training Program Scholarship

the Australian National Health and Medical Research Council (NHMRC) [#1044904]

Secondary Sponsor(s)

Centre for Research in Evidence-Based Practice, Bond University

Clinical Epidemiology and Evidence-Based Medicine Unit, Dr Cipto Mangunkusumo Hospital and Faculty of Medicine Universitas Indonesia

Ethics review

Status: Approved
Approval date:
Contact:

Bond University’s Human Research Ethics Committee (BUHREC)

Status: Approved
Approval date:
Contact:

The Ethics Committee of the Faculty of Medicine University of Indonesia

Results

• Results available: Yes
• Date Posted: 05/08/2019
• Date Completed: 19/02/2019