Topical Timolol for Infantile Hemangioma in Early Proliferative Phase

Study Overview
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Brief Summary
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Infantile hemangioma (IH) is the most common benign vascular tumor in pediatric population. Oral propranolol is the treatment of choice for complicated hemangiomas. Topical timolol, a non-selective beta-blocker, is an emerging treatment which has been reported to be effective and safe for the treatment of IH, especially for superficial hemangiomas. Investigators hypothesize that treatment with topical timolol in the first two months of life, before the proliferative phase or in early proliferative phase, may prevent from further growing and the need to treat with oral propranolol.

Detailed Description
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A multicentric, randomized, double-blind, placebo-controlled, phase II clinical trial to evaluate the efficacy and safety of 0.5% timolol maleate solution for the early treatment of infantile hemangioma. Patients with less of 60 days of life with focal or segmental hemangiomas, superficial, mixed or abortive will be treated with topical timolol 0.5% twice a day for 24 weeks. Changes in lesion size, color and thickness will be evaluated from photographs taken at 2,4,8,12,24 and 36 weeks. Vital signs and side effects will be recorded at each visit. Response to treatment will be evaluated by a blinded investigator in a semiquantitative scale (complete resolution, improve, stabilization, worsening).

Official Title
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Efficacy and Safety of Topical Timolol Maleate 0.5% Solution for Superficial Infantile Hemangioma in Early Proliferative Phase. A Randomized Clinical Trial

Conditions
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Hemangioma

Intervention / Treatment
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* Drug: Timolol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent for study participation and the use of the patient's photographs from the patient's parent(s) or guardian(s), The patient is between 10 and 60 days of age at the time of enrollment, The patient should have: at least one focal or segmental hemangioma, mixed or superficial, present anywhere on the body of at least 0.3 cm of minimum diameter and not greater of 5 cm. abortive or minimal growth hemangioma Infantile hemangioma precursors Exclusion Criteria: Patients > 60 days of age Complicated hemangiomas (life-threatening, function-threatening, or ulcerated) Children who have previously received systemic, intra-lesional or topical corticosteroids, imiquimod, vincristine, alpha-interferon, propranolol or other beta blockers, PDL laser. Patients with PHACES, LUMBAR, SACRAL or PELVIS syndrome. Internal involvement hemangiomas (liver, GI tract, larynx) Children with a personal history of asthma or cardiac conditions that may predispose to heart block. Children with congenital birth defects Children with Cancer (leukemia, sarcoma, neuroblastoma, retinoblastoma) Children with a history of hypersensitivity to beta blockers or excipients.

Ages Eligible for Study
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Minimum Age: 10 Days
Maximum Age: 60 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Timolol<br>Timolol maleate 0.5% topical solution; 50% of the patients treated (randomized) | Drug: Timolol<br>* The patient will be treated with 2 drops twice a day over the lesion and rub with the finger (no occlusive) for 24 weeks<br>* Other names: Timolol maleate 0.5%;|
| Placebo Comparator: Placebo<br>Saline topical solution; 50% of the patients treated (randomized) | Drug: Placebo<br>* The patient will be treated with 2 drops twice a day over the lesion and rub with the finger (no occlusive) for 24 weeks<br>* Other names: Saline Solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete or almost complete resolution of the lesions | Efficacy to treatment at 24 weeks, categorized as complete or almost complete resolution of the lesions (almost complete resolution defined as faint macular erythema, telangiectasia and no palpable component). This will be generated by independent blind evaluations by comparing photographs at baseline and 24 weeks. The investigators will score this improvement into one of the following categories (complete resolution, improve, stabilization, worsening) | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse reactions | Evaluation of safety and adverse reactions. The investigators will monitor vital signs of the patients every follow-up visit and ask the caretakers about side effects and adverse reactions to treatment. | 24 weeks |