Propranolol Versus Prednisolone for Treatment of Symptomatic Hemangiomas

Study Overview
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Brief Summary
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Hemangiomas are relatively common lesions in infants. Most go away spontaneously after one year of life and do not need treatment. Others require treatment because they cause significant symptoms such as pain, or difficulty with breathing, eating or ambulating. Steroids have classically been used to treat hemangiomas and help to shrink them in 1/3 - 2/3 of patients. Unfortunately, steroids have many side effects in babies so physicians have sought other ways to treat them. Recently, the use of propranolol, a heart medication, was serendipitously found to reduce the size of hemangiomas. It appears to have many fewer side effects than steroids but it is not yet known if it works as well as steroids. This study seeks to compare the effect and the side effects of propranolol versus steroids for treating hemangiomas that cause symptoms in infants.

Detailed Description
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Infants with symptomatic hemangiomas will be enrolled. Magnetic resonance imaging will be completed before starting medication if the extent of the hemangioma is not evident on clinical examination alone. Infants will be randomized to receive either propranolol or steroids for 4-6 months. Hemangioma response will be measured and compared monthly as will tolerability of the medications. Additionally, urine specimens will be collected at each visit to determine if markers are present that can predict response to therapy. Additionally, any hemangiomas that are excised will be examined for genetic markers to aid in predicting response to therapy.

Official Title
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Propranolol vs Prednisolone for Infant Hemangiomas-A Clinical and Molecular Study

Conditions
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Hemangioma of Infancy

Intervention / Treatment
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* Drug: propranolol
* Drug: Prednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: infants with symptomatic hemangiomas Exclusion Criteria: asthma diabetes hypertension hypotension hypoglycemia liver failure previous treatment for hemangiomas

Ages Eligible for Study
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Minimum Age: 2 Weeks
Maximum Age: 6 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: propranolol for treatment of hemangiomas<br>Assessing efficacy and tolerability of propranolol in management of symptomatic hemangiomas | Drug: propranolol<br>* propranolol 0.5 mg/kg orally, 4 per day - 4-6 months<br>|
| Active Comparator: Prednisolone<br>Assessing efficacy and tolerability of prednisolone in management of symptomatic hemangiomas and comparing to propranolol. | Drug: Prednisolone<br>* 1.0 mg/kg orally, 2 per day 4-6 months<br>* Other names: pediapred;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease in Size of Hemangioma (Length x Width) in Square mm | A priori primary outcome was proportional change in the total surface area as measured by lesion's outer margin length x width at baseline minus the same measure at 4 months with surrogate data used at 5 months if 4 months not available. | 4-5 months after initiating therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability of Medication | All adverse events relating to medication tolerability including: adrenal crisis, growth/development, constitutional (dehydration), allergy/immunology, dermatologic, endocrine, GI, infection, metabolism/labs, pulmonary, vascular. | enrollment until study close out or withdrawal up to 9 months | 
| Number of Serious Adverse Events (SAEs) | Number of serious adverse events experienced by the participants in each treatment arm within the categories adrenal crisis, growth/development, constitutional. Serious adverse events are defined as events that result in death, require either inpatient hospitalization or the prolongation of hospitalization, are life-threatening, result in a persistent or significant disability/incapacity, or result in a congenital anomaly/birth defect. Other important medical events, based upon appropriate medical judgment, may also be considered Serious Adverse Events if a trial participant's health is at risk and intervention is required to prevent an outcome mentioned. | enrollment until study close out or withdrawal up to 9 months | 
| Growth and Development Adverse Events | Number of Growth and Development AEs in each study arm | enrollment to study withdrawal or close out up to 9 months | 
| Pulmonary/Respiratory Adverse Events | Number of pulmonary/respiratory adverse events (CTCAE 22) in each study arm | enrollment through study close out or withdrawal, up to 9 months | 
| Allergy/Immunology Adverse Events | Number of allergy/immunology AE per study arm | enrollment through study closeout or study withdrawal up to 9 months | 
| Dermatologic Adverse Events | Number of Dermatologic Adverse Events in each study arm. | enrollment to study close out or withdrawal up to 9 months | 
| Endocrinologic Adverse Events | Number of Endocrinologic AEs (of which adrenal crisis does not overlap). | enrollment to close out or study withdrawal up to 9 months | 
| Gastrointestinal Adverse Events | Number of Gastrointestinal AEs in each arm | enrollment to study withdrawal or study close out up to 9 months | 
| Infectious Adverse Events | Number of infectious AEs in each study arm (i.e. conjunctivitis, thrush, fever) | enrollment to study withdrawal or close out up to 9 months | 
| Metabolic or Laboratory AEs | Number of Metabolic or Laboratory AEs in each study arm. | enrollment to study withdrawal or close out up to 9 months | 
| Vascular Adverse Events | Number of Vascular AEs in each study arm. | enrollment to study withdrawal or close out up to 9 months | 
| Constitutional Adverse Events | Number of constitutional AEs in each study arm. | enrollment to study close out or withdrawal up to 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hemangioma