Timolol Option for Ulcerated Hemangiomas (TOUCH Trial)

Study Overview
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Brief Summary
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The purpose of this study is to determine whether Timolol 0.5% Gel Forming Solution is safe and effective in promoting wound healing of infantile ulcerated hemangiomas compared with standard conservative management with topical antibiotic.

Detailed Description
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Ulceration is the most common complication associated with infantile hemangiomas. Ulceration and the delay in wound healing places patients at risk for infection, bleeding, pain and permanent scarring. Currently, the care of ulcerated hemangiomas is extremely difficult and patients are often subject to multiple treatment modalities. In the past two years, the leading advance in the treatment of hemangiomas has been the use of the non-selective, oral beta-blocker propranolol to arrest growth and promote involution of hemangiomas. Recent literature also suggests beta-blockers may have a role in helping ulcerated wounds re-epithelialize. The use of a topical non-selective beta-blocker on isolated ulcerated hemangiomas may promote early healing and reduce the number of complications associated with ulceration. Investigation is needed to explore the safety and tolerability of applying a topical beta-blocker on an ulcerated hemangioma and whether topical beta-blockade may be more efficacious than conservative care with topical antibiotics. In this study, infants will be randomized to either receive a topical antibiotic (topical mupirocin 2% ointment twice per day) or a topical beta-blocker (Timolol 0.5% Gel Forming Solution) according to a dose-escalation schedule. Subjects will be seen in clinic on day 7, day 14, 1 month and 2 months into therapy and 1 month after therapy is completed. Photographs and safety and efficacy measurements will be taken at each visit to assess response to therapy.

Official Title
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The Efficacy of Timolol 0.5% Gel Forming Solution for the Treatment of Ulcerated Hemangiomas

Conditions
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Infantile Hemangiomas

Intervention / Treatment
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* Drug: Timolol 0.5% Gel Forming Solution (GFS)
* Drug: Mupirocin 2% Ointment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants weighing between 4-12kg Infants with corrected gestational age 44 weeks - 8 months of age Infant with an ulcerated hemangioma Informed consent Exclusion Criteria: Ulceration larger than 16cm2 Ulcerated hemangioma with active bleeding or infection at time of enrollment Disease threatening hemangioma meeting criteria for oral propranolol Previous treatment with topical/oral corticosteroid or propranolol Medical history of congenital heart disease with decreased cardiac output, stroke/cerebral vasculopathy, active reactive airway disease or metabolic disorder History of an allergic reaction to Mupirocin or Timolol Currently taking medication that would interact with beta-blockers

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 8 Months

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Timolol 0.5% Gel Forming Solution (GFS)<br>Half of enrolled subjects will receive topical Timolol | Drug: Timolol 0.5% Gel Forming Solution (GFS)<br>* Dose-based escalation schedule for topical application: 4-8 kg: Day 0-7: 1 drop every other day; Day 7-14: 1 drop daily; Day 14 - Day 60: 1 drop twice per day 8-12 kg: Day 07: 1 drop daily; Day 7-14: 1 drop twice per day; Day 14 - Day 60: 2 drops twice per day<br>* Other names: Timolol 0.5% topical;|
| Active Comparator: Mupirocin 2% ointment<br>Half of enrolled subjects will receive Mupirocin | Drug: Mupirocin 2% Ointment<br>* Topical application twice per day for 60 days<br>* Other names: Mupirocin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Wound Re-epithelization |  | At 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in Ulcer Surface Area and Depth |  | At 3 months | 
| Investigator's Global Evaluation of Disease | A scoring system developed to measure clinical improvement of ulcerated hemangioma. | At 3 months | 
| Timolol Serum Level |  | Measured at 1 month into therapy | 
| Evaluate number of participants with changes in Glucose levels after drug is applied | Glucose monitoring will be performed for patients receiving Timolol 0.5% GFS before and 1 hour after drug is applied in clinic. Glucose values < 60 mg/dL will be considered significant. Subjects will be seen in clinic on day 7, day 14, 1 month and 2 months into therapy and 1 month after therapy is completed. | Baseline, day 7, day 14 | 
| Evaluate number of participants with evidence of changes in blood pressure following administration of Timolol 0.5% GFS | Blood pressure monitoring will be performed for patients receiving Timolol 0.5% GFS before and 1 hour after drug is applied in clinic. Blood pressure values < 3rd percentile (systolic or diastolic) will be considered significant for hypotension. Subjects will be seen in clinic on day 7, day 14, 1 month and 2 months into therapy and 1 month after therapy is completed. | Baseline, day 7, day 14 | 
| Pain scores (presence or absence) on the Wong-Baker faces scale | Investigators will question caregivers about common complications of ulcerated hemangiomas (pain, infection, bleeding) at each visit throughout the study. Pain will be assessed using the Wong-Baker faces scale. Subjects will be seen in clinic on day 7, day 14, 1 month and 2 months into therapy and 1 month after therapy is completed. | Baseline, day 7, day 14, 1 month, 2 months | 
| Number of participants with presence or absence of Infection | Investigators will question caregivers about common complications of ulcerated hemangiomas (pain, infection, bleeding) at each visit throughout the study. Infection will be clinically assessed by presence of drainage or exudate, and/or culture positivity. Subjects will be seen in clinic on day 7, day 14, 1 month and 2 months into therapy and 1 month after therapy is completed. | Baseline, day 7, day 14, 1 month, 2 months | 
| Number of participants with presence (or absence) of active bleeding | Investigators will question caregivers about common complications of ulcerated hemangiomas (pain, infection, bleeding) at each visit throughout the study. Infection will be clinically assessed by presence of active bleeding. Subjects will be seen in clinic on day 7, day 14, 1 month and 2 months into therapy and 1 month after therapy is completed. | Baseline, day 7, day 14, 1 month, 2 months | 
| Evaluate number of participants with changes in Heart Rate after drug is applied | Glucose and vital sign monitoring will be performed for patients receiving Timolol 0.5% GFS before and 1 hour after drug is applied in clinic. Heart rate values < 3rd percentile will be considered significant and indicative of bradycardia. Subjects will be seen in clinic on day 7, day 14, 1 month and 2 months into therapy and 1 month after therapy is completed. | Baseline, day 7, day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemangioma, Infantile Hemangioma, Ulcerated Hemangioma, Timolol, Beta blocker, Vascular anomaly