Topical Timolol for Infantile Hemangioma in Early Proliferative Phase

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

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.

Study Overview

• Status: Completed
• Conditions: Hemangioma
• Intervention / Treatment: Drug: Timolol; Drug: Placebo

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Sevilla, Spain, 41013
    • Hospital Virgen Del Rocio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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
Experimental: Timolol; Timolol maleate 0.5% topical solution; 50% of the patients treated (randomized)	Drug: Timolol; The patient will be treated with 2 drops twice a day over the lesion and rub with the finger (no occlusive) for 24 weeks; Other Names: Timolol maleate 0.5%
Placebo Comparator: Placebo; Saline topical solution; 50% of the patients treated (randomized)	Drug: Placebo; The patient will be treated with 2 drops twice a day over the lesion and rub with the finger (no occlusive) for 24 weeks; Other Names: Saline Solution

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
• Investigators: Principal Investigator: Eulalia Baselga, MD, PhD, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: November 17, 2015
• First Submitted That Met QC Criteria: April 6, 2016
• First Posted (Estimate): April 7, 2016

Study Record Updates

• Last Update Posted (Actual): November 14, 2018
• Last Update Submitted That Met QC Criteria: November 13, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Congenital Abnormalities; Skin Abnormalities; Neoplasms, Vascular Tissue; Hemangioma, Capillary; Port-Wine Stain; Hemangioma; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Timolol
• Other Study ID Numbers: IIBSP-TIM-2013-156