Topical Timolol for Superficial Infantile Hemangioma

Treatment of Cutaneous Hemangioma of Infancy With Topical 0.5% Timolol Maleate Eye Drop Compared With Placebo in Pediatric Patients, Siriraj Hospital

Infantile hemangioma (IH) is the most common benign vascular tumor in pediatric population. The characteristic natural history of this tumor is rapid growth in the first year of life and follows by spontaneous involution. However, it may cause cosmetic unacceptable. Early intervention in superficial IH may help to minimize the risk of residual aesthetic problems. Topical timolol, a non selective beta-blocker, is an emerging treatment which has been reported in efficacy and safety for the treatment of IH. However, the reported studies were case-series or small study. This study is a prospective double-blind,randomized-controlled study to evaluate the efficacy and safety of 0.5% timolol maleate solution for treatment in superficial IH. The patient will be treated with topical timolol for at least 6 months and instructed to 4 times daily apply 1-2 drop of timolol solution on the lesion and rub over the entire lesion with a finger. Photographs of the lesion will be taken at the baseline and every 1-month visit. Clinical evaluation of the treatment efficacy is carried out by 2 investigators independently to determine the change in lesion size and visual analogue scale of the lesion color. The main outcome is to evaluate the efficacy of 0.5% timolol maleate solution in treatment of infantile hemangioma compared to placebo.

Study Overview

• Status: Completed
• Conditions: Hemangioma
• Intervention / Treatment: Drug: Normal saline; Drug: 0.5% timolol maleate eye drop

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 3

Contacts and Locations

Study Locations

• Thailand
  • Bangkok
    • Bangkoknoi, Bangkok, Thailand, 10700
      • Faculty of medicine Siriraj Hospital Mahidol University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patient who is less than 2 years
• Patient who has been diagnosed with superficial infantile hemangioma
• The tumor which has been in proliferative or plateau phase
• There is no indication for systemic treatment
• Informed consent is obtained from the parent of the patient

Exclusion Criteria:

• Patient who has the indication for systemic therapy
• Patient who is treated by the other modality such as laser treatment
• Patient who has underlying disease treated by beta blocker, corticosteroids, interferon, cyclophosphamide or vincristine
• Patient who has history of hypersensitivity reaction to beta blocker, asthma, cardiac condition prove to heart block

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: normal saline; normal saline 1-2 drops put on the hemangioma lesion 4 times a day and rub over the entire lesion with a finger	Drug: Normal saline; Other Names: Saline
Experimental: 0.5% timolol maleate eye drop; 0.5% timolol maleate solution 1-2 drops put on the hemangioma lesion 4 times a day and rub over the entire lesion with a finger	Drug: 0.5% timolol maleate eye drop

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of the topical 0.5% timolol maleate solution in treatment of infantile hemangioma compared to placebo	Percent changes in visual analogue scale of the lesion color and global assessment scale of the lesion after treatment	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side effects of the topical 0.5% timolol maleate solution in treatment of infantile hemangioma	The side effects of 0.5% timolol maleate solution include bradycardia, dizziness, irritant contact dermatitis, allergic contact dermatitis, fatigue, nausea, diarrhea,and insomnia. To determine the side effects, investigators will monitor the vital signs of the patients every follow-up visit and ask the caretakers about the side effects. Furthermore, every patients will receive the dairy to record the frequency of drug usage and side effects found.	6 months

Collaborators and Investigators

• Sponsor: Mahidol University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2012
• Primary Completion (Actual): March 1, 2023
• Study Completion (Actual): March 1, 2023

Study Registration Dates

• First Submitted: September 5, 2012
• First Submitted That Met QC Criteria: September 11, 2012
• First Posted (Estimated): September 14, 2012

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; Hemangioma; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Pharmaceutical Solutions; Timolol; Ophthalmic Solutions
• Other Study ID Numbers: 088/2555(EC4)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO