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Trial registered on ANZCTR


Registration number
ACTRN12619001685101
Ethics application status
Approved
Date submitted
12/09/2019
Date registered
2/12/2019
Date last updated
2/12/2019
Date data sharing statement initially provided
2/12/2019
Date results information initially provided
2/12/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Randomised controlled trial: Can topical timolol maleate prevent complications and reduce the need for further treatment for small superficial infantile haemangiomata
in high risk areas?
Scientific title
Randomised controlled trial: Can topical timolol maleate prevent complications and reduce the need for further treatment for small superficial infantile haemangiomata
in high risk areas?
Secondary ID [1] 299258 0
None
Universal Trial Number (UTN)
U1111-1240-0756
Trial acronym
TTM PART4SmaSH
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infantile Haemangioma 314396 0
Condition category
Condition code
Skin 312731 312731 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Mode: Topical
Drug: 0.5% timolol maleate solution
Dose: 1 drop (0.25mg) per 10mm in length/width of haemangioma twice daily
Duration: 12 months

Our compliance is monitored by medical documentation based on patient reporting at our frequent regular follow ups. The patient is also dispensed the calculated amount of required medications by our pharmacy colleagues.
Intervention code [1] 315546 0
Treatment: Drugs
Intervention code [2] 315547 0
Prevention
Comparator / control treatment
No treatment
Control group
Active

Outcomes
Primary outcome [1] 321366 0
Data-linkage to medical records and direct clinical assessment by doctors at outpatient clinic for complications.

Complications include rapid increase in size (>150% per month increase in volume), development of ulceration, or impairment of vital functions of infantile haemangioma. The lesions are measured using a ruler for its size. The other parameters can be seen directly with the naked eye.
Timepoint [1] 321366 0
At baseline, 1 month, 3 months, 6 months and 12 months (primary endpoint) after randomisation
Primary outcome [2] 321367 0
Data-linkage to medical records and direct clinical assessment by doctors at outpatient clinic for any further treatment required.

Further treatment include oral propranolol, laser therapy, corticosteroid injection or surgical excision. Decision is based on development of complications which in turn aligns to HK, US and UK protocols.
Timepoint [2] 321367 0
At baseline, 1 month, 3 months, 6 months and 12 months (primary endpoint) after randomisation
Secondary outcome [1] 374778 0
Data-linkage to medical records and direct clinical assessment by doctors at outpatient clinic for any reported side effects of topical timolol maleate by the carers of the child.
Timepoint [1] 374778 0
At baseline, 1 month, 3 months, 6 months and 12 months after randomisation.
Secondary outcome [2] 374779 0
Size in terms of length, width and thickness of haemangioma measured with paper measuring ruler and documented with photo
Timepoint [2] 374779 0
At baseline, 1 month, 3 months, 6 months and 12 months after randomisation.

Eligibility
Key inclusion criteria
Chinese patients, patients less than 1 year old at first consultation within the study period, superficial infantile haemangioma ("IH"), IH less than 2cm in its longest diameter, and IH located in high risk areas (that is, tip of ears, tip of nose, eyelids, acral areas, facial areas, scalp, neck, buttocks, perineum and axilla).
Minimum age
1 Hours
Maximum age
1 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with pre-treated IH, IH with mixed or deep components, non-infantile haemangiomata such as non-involuting congenital haemangiomata (NICH), syndromal haemangiomata (e.g. PHACES syndrome), and IH that are already complicated or ulcerated at first consultation.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by coin tossing
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
We hypothesised that TTM is superior to watchful waiting for treatment of haemangiomas. Assuming that the percentage of uncomplicated IH without need for further intervention would be 62% 13, whilst that after the use of TTM would be 99% 16, and the superiority margin 0.05, the required sample size with equal (1:1) allocation to achieve an 80% power (= 0.2) and a = 0.05 is 60 subjects (30 subjects in each group). Assuming a 5% dropout rate, we planned to recruit a total of 64 subjects into this study, with 32 subjects in the TTM group and 32 subjects in the no-TTM group. The primary and secondary analyses of all outcomes followed the intention-to-treat principle.

Patient characteristics were presented as frequencies and percentages for categorical data and means (SD) or medians (IQR) for continuous data.

Statistical analysis was performed using the Statistical Package SPSS 23 software. Categorical data was compared using the chi-square test or the Fisher Exact test (for cells less than 5), and odds ratio (OR) with 95% confidence interval (C.I.) was calculated. Continuous variables were compared using the independent t test or Mann-Whitney U test. For the secondary outcome, percentage changes over time at 3 months, 6 months and 12 months after study uptake were compared. Flat IH and subjects who defaulted the 12-month follow-up session were excluded from the secondary outcome analysis, while missing data were kept the same as the last measured size. IH were excluded from the secondary outcome analysis upon receiving additional treatment. A two-sided p-value of = 0.05 was considered significant.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
23/11/2016
Date of last participant enrolment
Anticipated
Actual
23/12/2017
Date of last data collection
Anticipated
Actual
23/12/2018
Sample size
Target
64
Accrual to date
Final
41
Recruitment outside Australia
Country [1] 21855 0
Hong Kong
State/province [1] 21855 0
Kowloon

Funding & Sponsors
Funding source category [1] 303793 0
Self funded/Unfunded
Name [1] 303793 0
None
Country [1] 303793 0
Primary sponsor type
Hospital
Name
United Christian Hospital
Address
Department of Paediatrics and Adolescent Medicine, United Christian Hospital, 130 Hip Wo Street, Kwun Tong, Hong Kong SAR
Country
Hong Kong
Secondary sponsor category [1] 303916 0
None
Name [1] 303916 0
Address [1] 303916 0
Country [1] 303916 0
Other collaborator category [1] 280948 0
Hospital
Name [1] 280948 0
Hong Kong Children's Hospital
Address [1] 280948 0
Hong Kong Children's Hospital
1 Shing Cheong Road
Kowloon Bay
Kowloon
Hong Kong
Country [1] 280948 0
Hong Kong

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304313 0
Research Ethics Committee (Kowloon Central/Kowloon East)
Ethics committee address [1] 304313 0
Queen Elizabeth Hospital, 30 Gascoigne Road, Kowloon, HKSAR
Ethics committee country [1] 304313 0
Hong Kong
Date submitted for ethics approval [1] 304313 0
27/10/2016
Approval date [1] 304313 0
23/11/2016
Ethics approval number [1] 304313 0
KCKESOP001F6a

Summary
Brief summary
Objective: To define the role of topical timolol maleate (TTM) in the treatment of infantile haemangiomata (IH). We hypothesised that TTM is superior to watchful waiting for treatment of IH.
Study design: In this single-centre randomised controlled trial, we included all <1-year-old infants within a 13-month period presenting with small (<2cm) superficial IH located at high risk areas (i.e. tip of ears, tip of nose, eyelids, acral areas, facial areas, scalp, neck, buttocks, perineum and axilla). Patients either received 12 months of 0.5% timolol maleate solution (study group) or watchful waiting (control group). Both groups were monitored and treated similarly. The primary outcome was IH with development of complications that required additional interventions. The secondary outcomes included side effects of TTM and change in IH size.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 96498 0
Dr Cheng James Wesley Ching-hei
Address 96498 0
Department of Paediatrics and Adolescent Medicine, United Christian Hospital, 130 Hip Wo Street, Kwun Tong, Hong Kong SAR
Country 96498 0
Hong Kong
Phone 96498 0
+852 98238238
Fax 96498 0
Email 96498 0
[email protected]
Contact person for public queries
Name 96499 0
Dr Cheng James Wesley Ching-hei
Address 96499 0
Department of Paediatrics and Adolescent Medicine, United Christian Hospital, 130 Hip Wo Street, Kwun Tong, Hong Kong SAR
Country 96499 0
Hong Kong
Phone 96499 0
+852 98238238
Fax 96499 0
Email 96499 0
[email protected]
Contact person for scientific queries
Name 96500 0
Dr Luk Chi Kong David
Address 96500 0
Department of Paediatrics and Adolescent Medicine, United Christian Hospital, 130 Hip Wo Street, Kwun Tong, Hong Kong SAR
Country 96500 0
Hong Kong
Phone 96500 0
+852 39496135
Fax 96500 0
Email 96500 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data underlying published results only
When will data be available (start and end dates)?
Beginning 3 months and ending 5 years following main results publication
Available to whom?
Case-by-case basis at the discretion of Primary Sponsor
Available for what types of analyses?
Only to achieve the aims in the approved proposal,
How or where can data be obtained?
Access subject to approvals by Principal Investigator ([email protected])


What supporting documents are/will be available?




Results publications and other study-related documents

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

Documents added automatically
No additional documents have been identified.