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Trial registered on ANZCTR


Registration number
ACTRN12609000858291
Ethics application status
Approved
Date submitted
28/01/2009
Date registered
1/10/2009
Date last updated
16/12/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Looking for better treatments for impetigo in Aboriginal children
Scientific title
An open label randomised controlled trial to determine if 5 days of once-daily oral trimethoprim-sulfamethoxazole or three days of twice-daily oral trimethoprim-sulfamethoxazole will lead to non-inferior cure rates of impetigo compared to a single dose of intramuscular benzathine penicillin G (the current gold standard treatment) in children living in remote Aboriginal communities between the age of 12 weeks to less than 13 years.
Secondary ID [1] 282690 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Impetigo in Aboriginal children 4240 0
Condition category
Condition code
Skin 4462 4462 0 0
Other skin conditions
Infection 252143 252143 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 2: Trimethoprim-sulfamethoxazole oral suspension 8 + 40 mg/kg (max 320 + 1600 mg) daily for 5 days
Arm 3: Trimethoprim-sulfamethoxazole oral suspension 4 + 20 mg/kg (max 160 + 800 mg) twice daily for three days
Intervention code [1] 3964 0
Treatment: Drugs
Comparator / control treatment
Arm1: Single dose intramuscular benzathine penicillin G weight band based dosing up to 900mg. 3 - <6kg = 225mg; 6 - <10 kg = 337.5mg; 10 - >15kg = 450mg; 15 - <20kg = 675mg; >20kg = 900mg.
Control group
Active

Outcomes
Primary outcome [1] 5342 0
The proportion of children successfully treated on day 7 after the commencement of treatment within each of the respective groups.
Successfully treated is defined as a child with impetigo which has been clinically classified as sore either healed or improved by a person blinded to the allocated randomisation.
Timepoint [1] 5342 0
Day 7 after the commencement of treatment
Secondary outcome [1] 8976 0
The proportion of children within each of the respective groups who are defined as being successfully treated on day 2.
Timepoint [1] 8976 0
Day 2 after the commencement of treatment.
Secondary outcome [2] 8977 0
Prevalence of Staphylococcus aureus (methicillin susceptible and methicillin resistant) and Group A Streptococci per child at day 0, day 2 and day 7 within each treatment group as determined from impetigo swabs collected at the respective time points
Timepoint [2] 8977 0
Day 0, 2 and 7 after the commencement of treatment
Secondary outcome [3] 8978 0
Effect of each treatment on the bacterial resolution of sores at days 2 and 7 as determined by impetigo swabs collected at the respective timepoints
Timepoint [3] 8978 0
Day 2 and 7 after the commencement of treatment
Secondary outcome [4] 8979 0
Prevalence of nasal carriage of Staphylococcus aureus at baseline and day 7 (including a comparison of the prevalence of methicillin-resistant S. aureus at baseline and day 7).
Timepoint [4] 8979 0
Day 0 and 7 after the commencement of treatment
Secondary outcome [5] 8980 0
Evidence of allergy or other reaction to the medication within 7 days of first administration as determined by clinical observation and questioning of care givers
Timepoint [5] 8980 0
Within 7 days after the commencement of treatment
Secondary outcome [6] 303299 0
Comparison of BPG with each of the individual trimethoprim-sulphamethoxazole arms (3 days of twice daily or 5 days of daily dosing) at Day 7 and Day 2 for successful treatment. Successfully treated is defined as a child with impetigo which has been clinically classified as sore either healed or improved by a person blinded to the allocated randomisation.
Timepoint [6] 303299 0
Days 2 and 7 post commencement of treatment
Secondary outcome [7] 303300 0
Pooled results of all sores (not taking into account pairing or stratification) to determine treatment success. Successfully treated is defined as a child with impetigo which has been clinically classified as sore either healed or improved by a person blinded to the allocated randomisation.
Timepoint [7] 303300 0
Day 2 and Day 7 post commencement of treatment
Secondary outcome [8] 303301 0
Sores will be assessed clinically for treatment success by study staff who are aware of treatment allocation. This result will be compared with the result from the paired digital images assessed by experts who have been blinded to treatment allocation.
Timepoint [8] 303301 0
Days 2 and 7 post commencement of treatment

Eligibility
Key inclusion criteria
1. Age 12 weeks to less than 13 years at the time written consent is obtained
2. Diagnosis of purulent or crusted impetigo by criteria outlined in the Booklet “Recognising and Treating Skin Conditions” (East Arnhem Healthy Skin Program (EAHSP), Menzies School of Health Research 2006).
3. A resident in one of the participating communities at the time of enrolment and intending to stay in that community for the duration of the study (7 days post randomisation).
Minimum age
12 Weeks
Maximum age
13 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Receipt of any antibiotic in the previous seven days, or receipt of benzathine penicillin G (BPG) in the previous 30 days. 2. The presence of impetigo lesions that are only “flat-dry” (i.e. lesions that are not purulent or crusted) by criteria outlined in the Booklet “Recognising and Treating Skin Conditions” (EAHSP, Menzies School of Health Research 2006). 3. Known allergy to penicillin, sulphonamides or trimethoprim, or other constituents of study medications. 4. Immunocompromised, that is acquired, congenital or iatrogenic. 5. Previous participation in the trial in the last 90 days. 6. Evidence of sepsis, cellulitis, bullous impetigo, boils or carbuncles. 7. Intention by the patient or parent to use topical antibiotics. 8. Any condition that the principal investigator considers warrants exclusion from the trial.

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)
We will approach households with a local community health worker and request to screen children for skin sores. Children will also be identified by school and pre-school screening programs. For eligible children with impetigo, further explanation and consent will be requested to enter the trial and be randomised.
Eligible children will be randomised by the use of sealed, sequentially marked, opaque envelopes. Randomisation will be stratified by community and sore severity, to ensure an even distribution of community representation and severe or mild sores in each group. Sore severity will be classified as “mild” (<5 sores, of which no more than one is purulent) or “severe” (=5 sores or =2 purulent sores). In each community two sets of randomisation envelopes will be provided – one for mild and one for severe sores.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be stratified by sore severity, to ensure an even distribution of severe or mild sores in each group. We will use a permuted block design.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample Size calculation
This will be a non-inferiority study, designed to demonstrate that the alternative treatment arms give non-inferior cure rates to the current standard treatment (BPG) arm. We have defined noninferiority as a cure rate no more than 10% less than that of the current standard treatment arm, and have assumed a cure rate of 80% in the current standard treatment arm. Based on our expectation that the true difference between the alternative and the current standard treatment arms is zero, a sample size of 198 per group will allow us to demonstrate non-inferiority, with 80% power and a one-sided alpha of 0.05.

Target enrolment will be 660 subjects to provide 594 evaluable subjects (198 per group) assuming 10% withdrawal and/or loss to follow-up over the total study period.

Participant groups for analysis
All participants randomised will be analysed in the groups to which they were assigned.

Demographic analyses
Demographic data will be tabulated and expressed as proportions and/or means of the selected characteristics by study group with the corresponding 95% Confidence Intervals (CI). Differences between groups will be assessed by the normal test for comparison of means and chi2 tests for comparison of proportions.

Primary endpoint analysis
The primary outcome is binomial; therefore the test for two proportions will be used. Confidence intervals will be calculated using the normal distribution.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/12/2009
Actual
26/11/2009
Date of last participant enrolment
Anticipated
30/11/2012
Actual
20/11/2012
Date of last data collection
Anticipated
Actual
Sample size
Target
660
Accrual to date
Final
663
Recruitment in Australia
Recruitment state(s)
NT
Recruitment postcode(s) [1] 6984 0
0822 - Bathurst Island
Recruitment postcode(s) [2] 6985 0
0822 - Galiwinku
Recruitment postcode(s) [3] 6986 0
0822 - Maningrida
Recruitment postcode(s) [4] 6987 0
0822 - Milingimbi

Funding & Sponsors
Funding source category [1] 4421 0
Government body
Name [1] 4421 0
National Health and Medical Research Council (NHMRC) Project grant (545234)
Country [1] 4421 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Menzies School of Health Research
Address
PO Box 41096 Casuarina, 0811, NT
Country
Australia
Secondary sponsor category [1] 3982 0
None
Name [1] 3982 0
Address [1] 3982 0
Country [1] 3982 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6471 0
Human Research Ethics Committee of the Northern Territory Department of Health and Families and Menzies School of Health Research
Ethics committee address [1] 6471 0
Ethics committee country [1] 6471 0
Australia
Date submitted for ethics approval [1] 6471 0
28/01/2009
Approval date [1] 6471 0
18/09/2009
Ethics approval number [1] 6471 0
09/08

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29222 0
Prof Jonathan Carapetis
Address 29222 0
Telethon Institute for Child Health Research
100 Roberts Road, Subiaco, Western Australia, 6008
PO Box 855, West Perth, Western Australia, 6872
Country 29222 0
Australia
Phone 29222 0
+61 8 9489 7967
Fax 29222 0
Email 29222 0
jonathan.carapetis@telethonkids.edu.au
Contact person for public queries
Name 12469 0
Jane Nelson
Address 12469 0
Menzies School of Health Research
PO Box 41096 Casuarina, 0811, NT
Country 12469 0
Australia
Phone 12469 0
+61 8 8922 8196
Fax 12469 0
Email 12469 0
jane.nelson@menzies.edu.au
Contact person for scientific queries
Name 3397 0
Ross Andrews
Address 3397 0
Menzies School of Health Research
PO Box 41096 Casuarina, 0811, NT
Country 3397 0
Australia
Phone 3397 0
+61 8 8922 8196
Fax 3397 0
Email 3397 0
ross.andrews@menzies.edu.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseThe microbiology of impetigo in indigenous children: associations between Streptococcus pyogenes, Staphylococcus aureus, scabies, and nasal carriage.2014https://dx.doi.org/10.1186/s12879-014-0727-5
EmbaseThe importance of scabies coinfection in the treatment considerations for impetigo.2016https://dx.doi.org/10.1097/INF.0000000000001013
N.B. These documents automatically identified may not have been verified by the study sponsor.