Corticosteroids With Placebo Versus Corticosteroids With Propranolol Treatment of Infantile Hemangiomas (IH)

Study Overview
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Brief Summary
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This is a prospective randomized, double-blind study to compare the clinical efficacy of infantile hemangioma treatment using propranolol with corticosteroids as compared to therapy with corticosteroids and placebo. We hypothesize that a two-month treatment period with propranolol plus corticosteroids is more effective at reducing infantile hemangioma size and vascularity when compared to corticosteroids used without propranolol for the same time period.

Detailed Description
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Infantile hemangiomas (IH) are the most common head and neck pediatric tumors. Presence of these tumors can lead to complications of vision and airway compromise, bleeding and disfigurement. Medical treatment of these lesions has traditionally been focused on stopping new blood vessel growth with corticosteroids. Recent reports and our own experience have demonstrated that significant reduction in IH size and vascularity can also occur through the use of propranolol. Our initial experience with propranolol has demonstrated significant efficacy with fewer side effects than corticosteroids. Despite this experience, the standard of care for initial IH medical therapy remains corticosteroids. This Trial is a direct comparison of traditional IH therapy with corticosteroids to newer therapy with propranolol and corticosteroids.

Official Title
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A Phase II, Randomized, Double-Blind Comparison of Corticosteroid and Corticosteroids With Propranolol Treatment of Infantile Hemangiomas (IH)

Conditions
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Hemangioma

Intervention / Treatment
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* Drug: Prednisolone (Corticosteroid)
* Drug: Propranolol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 0 to < 9months Patients with clinical, radiographic or histologic diagnosis of infantile hemangioma (IH) requiring medical treatment IH patients whose parents desire medical treatment for the IH Stable cardiac function Exclusion Criteria: IH patients over 9 months of age. Hypersensitivity to propranolol Untreated heart failure: If the patient has heart failure associated with the hemangioma, propranolol would be initiated after anti-congestive therapy and under observation as an in-patient. Atrioventricular (AV) block Resting heart < 2 SD of normal*(below) Resting blood pressure < 2 SD of normal**(below) Wolff-Parkinson-White syndrome (WPW) History of unexplained syncope Bronchial asthma History of impaired renal or liver function Diabetes mellitus

Ages Eligible for Study
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Maximum Age: 9 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group A: Corticosteroid with Placebo<br>Group A will receive oral, liquid Prednisolone, which is the standard corticosteroid that we use here at Seattle Children's, and oral liquid placebo. The dose of prednisolone that Group A will receive will be 1-2mg/kg/day for 7 days and then the dose will be slowly reduced and then stopped after 3 weeks. This is a standard dose for IH treatment. Gastric prophylaxis (Zantac) will be given to help prevent any stomach problems associated with prednisolone. This treatment will be given for two months, as is our standard practice. | Drug: Prednisolone (Corticosteroid)<br>* Oral liquid prednisolone. Dose: 1-2mg/kg/day for 7 days, and then dose will be slowly reduced and then stopped after 3 weeks.<br>* Other names: Corticosteroids;Drug: Placebo<br>* Liquid placebo will be given during the two month treatment trial.<br>* Other names: Inactive medicine;|
| Other: Group B: Corticosteroid with Propranolol<br>Group B will receive oral liquid prednisolone, and oral propranolol. As in Group A, the dose of prednisolone will be 1-2mg/kg/day for 7 days and then the dose will be slowly reduced and then stopped after 3 weeks. Oral liquid propranolol will be dosed at 2 mg/kg/day, following initiation in the Cardiology Clinic. Gastric prophylaxis (Zantac) will be given to help prevent any stomach problems associated with prednisolone. | Drug: Prednisolone (Corticosteroid)<br>* Oral liquid prednisolone. Dose: 1-2mg/kg/day for 7 days, and then dose will be slowly reduced and then stopped after 3 weeks.<br>* Other names: Corticosteroids;Drug: Propranolol<br>* Oral liquid propranolol will be dosed Oral liquid propranolol will be dosed at 2 mg/kg/day.<br>* Other names: Propranolol hydrochloride (USP/EP) Oral Solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare Changes in IH Size and Vascularity for the Two Treatment Groups | This outcome cannot be evaluated. Trial limited by lack of patient family to have randomization, which limited the number of participants and made the project nonviable. | 1, 2, and 6 months after treatment initiation | 
| Lesion Regression | measure of change in lesion area or volume | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine Therapeutic Response of IH to Propranolol Among Patients Who Switch to Corticosteroids Plus Propranolol Therapy After Failing to Respond to Corticosteroids Alone. | This outcome cannot be evaluated. Trial limited by lack of patient family to have randomization, which limited the number of participants and made the project nonviable. | 1, 2, and 6 months after treatment initiation | 
| Assess the Safety of Propranolol With Corticosteroids and Corticosteroids Alone in the Treatment of IH. | This outcome cannot be evaluated. Trial limited by lack of patient family to have randomization, which limited the number of participants and made the project nonviable. | 1, 2 and 6 months after treatment initiation | 
| Demonstrate How Duplex Scanning to Assess Blood Vessel Density and Qualitative Color Ratings of Cutaneous Lesions From Photographs Can be Used to Measure and Quantify Changes in IH Size and Vascularity in a Clinically Relevant Manner. | This outcome cannot be evaluated. Trial limited by lack of patient family to have randomization, which limited the number of participants and made the project nonviable. | 1, 2 and 6 months after treatment initiation |