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

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

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.

Study Overview

• Status: Terminated
• Conditions: Hemangioma
• Intervention / Treatment: Drug: Prednisolone (Corticosteroid); Drug: Placebo; Drug: Propranolol

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 9 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Group A: Corticosteroid with Placebo; 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); Oral liquid prednisolone. Dose: 1-2mg/kg/day for 7 days, and then dose will be slowly reduced and then stopped after 3 weeks.; Other Names: Corticosteroids; Drug: Placebo; Liquid placebo will be given during the two month treatment trial.; Other Names: Inactive substance; Inactive drug; Inactive medicine
Other: Group B: Corticosteroid with Propranolol; 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); Oral liquid prednisolone. Dose: 1-2mg/kg/day for 7 days, and then dose will be slowly reduced and then stopped after 3 weeks.; Other Names: Corticosteroids; Drug: Propranolol; Oral liquid propranolol will be dosed Oral liquid propranolol will be dosed at 2 mg/kg/day.; Other Names: Propranolol hydrochloride (USP/EP) Oral Solution

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Seattle Children's Hospital
• Investigators: Principal Investigator: Jonathan A Perkins, DO, Seattle Children's Hospital

Publications and helpful links

General Publications

• Cushing SL, Boucek RJ, Manning SC, Sidbury R, Perkins JA. Initial experience with a multidisciplinary strategy for initiation of propranolol therapy for infantile hemangiomas. Otolaryngol Head Neck Surg. 2011 Jan;144(1):78-84. doi: 10.1177/0194599810390445.
• Truong MT, Perkins JA, Messner AH, Chang KW. Propranolol for the treatment of airway hemangiomas: a case series and treatment algorithm. Int J Pediatr Otorhinolaryngol. 2010 Sep;74(9):1043-8. doi: 10.1016/j.ijporl.2010.06.001. Epub 2010 Jul 31.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: February 22, 2010
• First Submitted That Met QC Criteria: February 23, 2010
• First Posted (Estimate): February 24, 2010

Study Record Updates

• Last Update Posted (Actual): October 4, 2018
• Last Update Submitted That Met QC Criteria: September 4, 2018
• Last Verified: September 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; Vasodilator Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Propranolol; Prednisolone
• Other Study ID Numbers: 12901