Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000234617
Ethics application status
Approved
Date submitted
25/02/2014
Date registered
5/03/2014
Date last updated
11/02/2021
Date data sharing statement initially provided
11/02/2021
Date results information initially provided
11/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparing cotrimoxazole and/or povidone-iodine ear wash with standard dry mopping and ciprofloxacin ear drops in Indigenous children with chronic suppurative otitis media (CSOM)
Scientific title
Among Aboriginal children (2 months of age and up to 17 years of age) with chronic suppurative otitis media, is oral cotrimoxazole (for 4 months) and/or povidone-iodine ear wash (until ear discharge resolves) in addition to standard treatment (cleaning and dry mopping with tissue spears plus topical ciprofloxacin until ear discharge resolves) superior to standard treatment alone for resolving ear discharge? A 2x2 factorial randomised controlled trial
Secondary ID [1] 283733 0
Nil
Universal Trial Number (UTN)
U1111-1151-1772
Trial acronym
I HEAR BETA (Indigenous Healthy EARs- BEtadine, Tissues and Antibiotics)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
chronic suppurative otitis media (CSOM) 290701 0
Condition category
Condition code
Ear 291069 291069 0 0
Other ear disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oral Intervention: Placebo or Sulfamethoxazole-trimethoprim (cotrimoxazole, 4mg/kg per dose of trimethoprim component) given orally twice daily for 16 weeks.

Topical Intervention: Povidone-iodine 0.5% (Betadine 'registered trademark') given twice daily as an ear wash (1:20 mixed with clean water), >=20mls per discharging ear. This treatment will be given prior to the standard recommended treatment of dry mopping with tissue spears and ciprofloxacin drops. Topical treatment regimens should continue until the ear has been without discharge for 3 days (confirmed on two clinical examinations at least 3 days apart).

Children will be randomised into one of four treatment arms. All treatments will commence at the same time (day one at randomisation). All arms will receive standard recommended topical treatment (dry mopping with tissue spears and ciprofloxacin drops 5 drops twice a day) PLUS either:

ARM 1: Oral cotrimoxazole and topical Povidone-iodine ear washouts or,

ARM 2: Oral cotrimoxazole and NO topical Povidone-iodine ear washouts or,

ARM 3: Oral placebo and topical Povidone-iodine ear washouts or,

ARM 4: Oral placebo and NO topical Povidone-iodine ear washouts.

Children who respond to treatment and then develop a recurrence of ear discharge will receive their original allocated topical treatment regimen.

Families will be shown how to perform the ear washes and given treatment packs. To measure adherence, we will ask families to return their used or unused treatment packs and ask families during follow-up phone calls and at the 16 week check-up about their treatment preferences and compliance issues.
Intervention code [1] 288426 0
Treatment: Drugs
Comparator / control treatment
There is one control arm (standard treatment only- no oral or additional topical intervention) and 3 comparator arms.

Oral comparator/control: A placebo medication that is identical in appearance, smell and taste as cotrimoxazole.

Topical comparator: no povidone-iodine wash.

Standard topical treatment (Northern Territory) for all children: Dry mopping with tissue spears and ciprofloxacin drops 5 drops twice a day.

Treatment regimens should continue until the ear has been without discharge for 3 days (confirmed on two clinical examinations at least 3 days apart).

Children who respond to treatment and then develop a recurrence of ear discharge will receive their original allocated topical treatment regimen.

Families will be shown how to perform the ear washes and given treatment packs.
Control group
Placebo

Outcomes
Primary outcome [1] 291066 0
Failure will be defined as presence of ear discharge in either ear, assessed by a trained research nurse using video-otoscopy before cleaning the ear canal.

The primary analysis will report the absolute risk difference and 95% confidence interval for:
(i) The difference in failure rates between children allocated to receive the povidone-iodine ear wash plus standard treatment, and children allocated to receive standard treatment alone;
(ii) The difference in failure rates between children allocated to receive twice daily oral cotrimoxazole and children allocated to receive placebo.
Timepoint [1] 291066 0
16 weeks (at the end of the intervention period)
Secondary outcome [1] 305946 0
Rates of clinical failure 12 months after randomisation will be analysed using an intention to treat analysis. Failure will be defined as presence of ear discharge in either ear, assessed by a trained research nurse using video-otoscopy before cleaning the ear canal.
Timepoint [1] 305946 0
12 months (at the end of the study)

Eligibility
Key inclusion criteria
Indigenous children 2 months to 17 years of age and residing in participating communities, with a diagnosis of unilateral or bilateral chronic suppurative otitis media (CSOM) are eligible to participate in this study.
Minimum age
2 Months
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Children who are ineligible include those who; i) have been previously randomised; ii) have ciprofloxacin, cotrimoxazole or iodine allergy; iii) had mastoid surgery in the preceding 12 months; iv) have ear surgery scheduled in the next 4 months; v) have congenital ear or hearing problems; vi) are known to have immunodeficiency; or vii) are pregnant.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Parents of children identified by their health care provider as having CSOM will be advised of the study and if agreeable will be referred to the research staff. Concealed allocation will be achieved by phone randomisation system provided by the NHMRC Clinical Trial Centre which will receive participant information then generate the randomisation number and allocation group (topical treatment code and the oral medication treatment codes).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Children will be stratified according to: i) community; and ii) age group (<3y; 3-10y; >10y). A computer generated sequence will be managed by the NHMRC Clinical Trials Centre. Block size and method will be concealed from all study staff and investigators.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Factorial
Other design features
Participants, health care providers, outcome assessors and data analysts will be blinded to the oral treatment/ component of this trial.
Data analysts will also be blinded to the topical treatment/ component of this trial.
Participants, health care providers and outcome assessors will not be blinded to the topical intervention.
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
We estimate that with 280 children randomised, this study will have ~88% power to detect an improved outcome in an additional 20% of children for each intervention (at the 5% significance level), assuming 10% loss to follow up. A full detailed statistical analysis plan will be developed and approved by all CIs before any outcome data are analysed.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
2/02/2015
Actual
9/03/2015
Date of last participant enrolment
Anticipated
1/12/2016
Actual
31/12/2017
Date of last data collection
Anticipated
Actual
31/12/2018
Sample size
Target
280
Accrual to date
Final
280
Recruitment in Australia
Recruitment state(s)
NT

Funding & Sponsors
Funding source category [1] 288429 0
Government body
Name [1] 288429 0
National Health and Medical Research Council (NHMRC)
Country [1] 288429 0
Australia
Primary sponsor type
Government body
Name
Menzies School of Health Research
Address
Darwin (Royal Darwin Hospital Campus)
John Matthews Building (JMB)
Building 58, Royal Darwin Hospital Campus,
Tiwi, NT 0811
Country
Australia
Secondary sponsor category [1] 287132 0
Government body
Name [1] 287132 0
Northern Territory Department of Health (DoH)
Address [1] 287132 0
87 Mitchell Street, Darwin, NT 0800
Country [1] 287132 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290303 0
Human Research Ethics Committee of Northern Territory Department of Health and Menzies School of Health Research SC00153
Ethics committee address [1] 290303 0
POBox 41096
Casuarina
NT
0811 Australia
Ethics committee country [1] 290303 0
Australia
Date submitted for ethics approval [1] 290303 0
12/03/2014
Approval date [1] 290303 0
29/04/2014
Ethics approval number [1] 290303 0
Ethics committee name [2] 290304 0
Central Australian Human Research Ethics Committee
Ethics committee address [2] 290304 0
Department of Health and Community Services
PO Box 721
Alice Springs
NT 0871
Ethics committee country [2] 290304 0
Australia
Date submitted for ethics approval [2] 290304 0
04/04/2014
Approval date [2] 290304 0
14/05/2014
Ethics approval number [2] 290304 0
HREC-14-228

Summary
Brief summary
This is a 2x2 factorial design randomised controlled trial of 4 months therapy with oral cotrimoxazole versus placebo and topical povidone iodine versus no wash, in addition to standard treatment to resolve chronic suppurative otitis media (runny ears) in children 2 months to less than 17 years of age. Standard treatment is twice daily dry mopping and topical ciprofloxacin drops.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 44858 0
Prof Peter Morris
Address 44858 0
Menzies School of Health Research
PO Box 41096
Casuarina, Northern Territory, 0811
Country 44858 0
Australia
Phone 44858 0
+61 8 8946 8570
Fax 44858 0
No fax
Email 44858 0
peter.morris@menzies.edu.au
Contact person for public queries
Name 44859 0
Prof Amanda Leach
Address 44859 0
Menzies School of Health Research
PO Box 41096
Casuarina, Northern Territory, 0811
Country 44859 0
Australia
Phone 44859 0
+61 8 8946 8560
Fax 44859 0
no fax
Email 44859 0
amanda.leach@menzies.edu.au
Contact person for scientific queries
Name 44860 0
Prof Amanda Leach
Address 44860 0
Menzies School of Health Research
PO Box 41096
Casuarina, Northern Territory, 0811
Country 44860 0
Australia
Phone 44860 0
+61 8 8946 8560
Fax 44860 0
nil
Email 44860 0
amanda.leach@menzies.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data is confidential


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes BMC Pharmacology and Toxicology (2019) 365450-(Uploaded-28-07-2020-11-24-40)-Journal results publication.pdf
Plain language summaryNo To be published

Documents added automatically
SourceTitleYear of PublicationDOI
EmbasePovidone-iodine ear wash and oral cotrimoxazole for chronic suppurative otitis media in Australian aboriginal children: Study protocol for factorial design randomised controlled trial.2019https://dx.doi.org/10.1186/s40360-019-0322-x
EmbaseMicrobiology of otitis media in Indigenous Australian children: Review.2017https://dx.doi.org/10.1017/S0022215116009294
N.B. These documents automatically identified may not have been verified by the study sponsor.