Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001370190
Ethics application status
Approved
Date submitted
27/08/2019
Date registered
8/10/2019
Date last updated
17/08/2022
Date data sharing statement initially provided
8/10/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Treatment of Superficial Strawberry Birthmarks with Topical Timolol
Scientific title
Topical Timolol Treatment of Superficial Proliferating Infantile Haemangioma assessing the effectiveness of 0.5% topical timolol gel in the treatment of
superficial IH.
Secondary ID [1] 298995 0
None
Universal Trial Number (UTN)
U1111-12113953
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infantile Haemangioma 314001 0
Condition category
Condition code
Skin 312390 312390 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is an open labelled phase II study assessing the effectiveness of 0.5% topical timolol gel in the treatment of superficial infantile haemangiomas (IHs) .
Most IHs do not require active treatment as they involute spontaneously over time. However, up to 10-15% of IH require intervention during infancy because they cause complications, such as visual and airway obstruction, ulceration, bleeding, and permanent disfigurement. Following spontaneous involution, approximately 50% of the lesions will leave a blemish, and half of these will require treatment. Currently propanolol is the mainstay treatment of problematic IHs. We have demonstrated that oral propranolol at 1.5–2 mg/kg/day is an effective and safe treatment for problematic proliferating IH. However, many of the untreated IH can cause permanent cosmectic blemish, affecting the skin and/or leaving subcutaneous fatty residuum following spontaneous involution. Earlier treatment (during the early proliferative phase) has been shown to result in better outcomes and reduced short and long-term complications.
Parents/caregivers will be shown how to apply this gel to the IH.
1 drop morning and night applied topically to the IH.
Treatment will be increased to 1 drop three times a day, morning,noon and night, after 2 months if there is no improvement and there are no adverse effects.
Treatment is continued until complete resolution of the lesion occurs, there is no change in lesion size, colour or consistency after 3 months of continued use, until the patient reaches 12 months of age, or if any criteria for removal from the study are met.
Intervention code [1] 315262 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 321046 0
Composite primary outcome
To assess the effectiveness of 0.5% topical timolol gel in the treatment of infantile haemangioma using an Analogue scale 0-10.
Before and after treatment photographs will be evaluated by an independent panel using an analogue scale of 0 (no improvement and/or deterioration) to 10 (excellent improvement).
Similarly, the parents/caregivers will be asked to evaluate the results of the treatment using this analogue scale.

Treatment failure will be defined as:
• A score of “0” on the analogue scale above
• Cessation of the growth of the lesion without regression in size, or improvement in consistency or colour
• Continued growth of the lesion
• Development of ulceration of the lesion or worsening of ulceration
Timepoint [1] 321046 0
Baseline at first clinic appointment.
4 weeks after commencement of treatment
12 weeks after commencement of treatment
24 weeks after commencement of treatment
52 weeks primary endpoint
Primary outcome [2] 321331 0
Possible adverse effect. decreased heart rate and blood pressure. Assessed at clinic appointments using digital sphygmomanometer.
Timepoint [2] 321331 0
Heart rate and blood pressure measured pre-commencement of treatment.
1 hour post treatment commencement
1 month after commencement of treatment
3 m0nths after commencement of treatment
6 months after commencement of treatment
12 months primary endpoint
Secondary outcome [1] 373788 0
Nil
Timepoint [1] 373788 0
Nil

Eligibility
Key inclusion criteria
Infants referred with a superficial IH(s) in the cosmetic sensitive areas (face and neck), perineum, buttock and axilla, who are not suitable for oral propranolol treatment.
Minimum age
1 Months
Maximum age
10 Months
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Premature infants (less than 6 weeks corrected gestational age)
• IH on or near mucosal surface such as the eye, mouth and anus
• Any single lesion larger than 90mm² (e.g., 3x3cm)
• Multifocal IHs with a total surface area of more than 90mm²
• IH with ulceration >1x1cm
• IH with thickness >3mm
• Subcutaneous IH
• Any infants with contraindication to ß-blocker use, e.g.:
o Cardiac disease including: 2nd or 3rd degree atrioventricular heart block, bradycardia, cardiac failure, cardiogenic shock and congenital heart disease
o Congenital hyperthyroidism
o Hypersensitivity to any components of the medication
• Weight <3.5kg
• >10 months old
• Premature infants with a history of apnoea or chronic lung disease

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
31/08/2018
Date of last participant enrolment
Anticipated
5/04/2023
Actual
Date of last data collection
Anticipated
7/06/2023
Actual
Sample size
Target
50
Accrual to date
22
Final
Recruitment outside Australia
Country [1] 21761 0
New Zealand
State/province [1] 21761 0

Funding & Sponsors
Funding source category [1] 303533 0
Other Collaborative groups
Name [1] 303533 0
Gillies McIndoe Research Institute
Country [1] 303533 0
New Zealand
Primary sponsor type
Other Collaborative groups
Name
Gillies McIndoe Research Institute
Address
Gillies McIndoe Research Institute
PO Box 7184
Newtown
Wellington
6242
New Zealand
Country
New Zealand
Secondary sponsor category [1] 303599 0
None
Name [1] 303599 0
Address [1] 303599 0
Country [1] 303599 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304060 0
Central Health and Ethics Disability Committee
Ethics committee address [1] 304060 0
Ministry of Health
PO box 5013
Wellington
6011
Ethics committee country [1] 304060 0
New Zealand
Date submitted for ethics approval [1] 304060 0
11/04/2018
Approval date [1] 304060 0
07/06/2018
Ethics approval number [1] 304060 0
18/CEN/67

Summary
Brief summary
Most IHs do not require active treatment as they involute spontaneously over time. Up to 10-15% of IHs are problematic and require intervention during infancy- with the mainstay treatment being oral propanolol. Complications of propranolol treatment of IH have been reported in up to 31% of patients in a large meta-analysis, and therefore its use is restricted to problematic IHs. However, following spontaneous involution, many of the IH lesions can cause permanent cosmetic blemish, Timolol maleate is a topical ß-blocker that has been used for the treatment of glaucoma in the paediatric population for over 30 years. Research is yet to define the optimal duration of topical treatment of IH, with studies treating patients from 24 weeks up to 10 months, or until satisfactory improvement was noted. The best outcomes for topical timolol appears to be in patients with superficial IH who used the 0.5% timolol solution for a period of at least three months.This study investigates the efficacy of 0.5% topical timolol gel for the treatment of superficial IHs.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 95686 0
Dr Swee Tan
Address 95686 0
Gillies McIndoe Research Institute
PO Box 7184
Newtown
Wellington
6242
Country 95686 0
New Zealand
Phone 95686 0
+64 216 31000
Fax 95686 0
Email 95686 0
swee.tan@gmri.org.nz
Contact person for public queries
Name 95687 0
Mrs Ruth Watson-Black
Address 95687 0
Gillies McIndoe Research Institute
PO Box 7184
Newtown
Wellington
6242
Country 95687 0
New Zealand
Phone 95687 0
+64277460776
Fax 95687 0
Email 95687 0
ruth.watson-black@gmri.org.nz
Contact person for scientific queries
Name 95688 0
Dr Swee Tan
Address 95688 0
Gillies McIndoe Research Institute
PO Box 7184
Newtown
Wellington
6242
Country 95688 0
New Zealand
Phone 95688 0
+64 216 31000
Fax 95688 0
Email 95688 0
swee.tan@gmri.org.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All de-identified data collected during the trial will be shared.
When will data be available (start and end dates)?
Data will be available after publication of the outcomes (and any protection of IP). No specific end date of when data will be shared has been decided as yet.
Available to whom?
Researchers in Infantile Haemangioma (IH)
Available for what types of analyses?
No restrictions on analyses are predicted.
How or where can data be obtained?
Requests are made to the Principal Investigator via email or website
https://www.gmri.org/ or swee.tan@gmri.org.nz
Dr Swee Tan
Gillies McIndoe Research Institute
PO Box 7184
Newtown
Wellington
6242
New Zealand


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
3988Study protocol  info@gmri.org.nz 378157-(Uploaded-12-08-2019-11-12-08)-Study-related document.docx
3989Ethical approval  info@gmri.org.nz 378157-(Uploaded-12-08-2019-11-12-42)-Study-related document.pdf



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.