Propranolol Versus Prednisolone for Treatment of Symptomatic Hemangiomas

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

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.

Study Overview

• Status: Terminated
• Conditions: Hemangioma of Infancy
• Intervention / Treatment: Drug: propranolol; Drug: Prednisolone

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20111
      • Children's National Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 weeks to 6 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• infants with symptomatic hemangiomas

Exclusion Criteria:

• asthma
• diabetes
• hypertension
• hypotension
• hypoglycemia
• liver failure
• previous treatment for hemangiomas

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Nancy Bauman
• Investigators: Principal Investigator: Nancy M Bauman, MD, Children's Research Institute, Children's National Medical Center

Publications and helpful links

General Publications

• Perez RS, Mora PC, Rodriguez JD, Sanchez FR, de Torres Jde L. [Treatment of infantile hemangioma with propranolol]. An Pediatr (Barc). 2010 Feb;72(2):152-4. doi: 10.1016/j.anpedi.2009.05.019. Epub 2009 Jul 23. No abstract available. Spanish.
• Denoyelle F, Leboulanger N, Enjolras O, Harris R, Roger G, Garabedian EN. Role of Propranolol in the therapeutic strategy of infantile laryngotracheal hemangioma. Int J Pediatr Otorhinolaryngol. 2009 Aug;73(8):1168-72. doi: 10.1016/j.ijporl.2009.04.025. Epub 2009 May 29.
• Leaute-Labreze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Taieb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008 Jun 12;358(24):2649-51. doi: 10.1056/NEJMc0708819. No abstract available.
• Bauman NM, McCarter RJ, Guzzetta PC, Shin JJ, Oh AK, Preciado DA, He J, Greene EA, Puttgen KB. Propranolol vs prednisolone for symptomatic proliferating infantile hemangiomas: a randomized clinical trial. JAMA Otolaryngol Head Neck Surg. 2014 Apr;140(4):323-30. doi: 10.1001/jamaoto.2013.6723.
• Patel NJ, Bauman NM. How should propranolol be initiated for infantile hemangiomas: inpatient versus outpatient? Laryngoscope. 2014 Jun;124(6):1279-81. doi: 10.1002/lary.24363. Epub 2013 Dec 17. No abstract available.

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: August 26, 2009
• First Submitted That Met QC Criteria: August 26, 2009
• First Posted (Estimate): August 27, 2009

Study Record Updates

• Last Update Posted (Estimate): February 24, 2016
• Last Update Submitted That Met QC Criteria: January 27, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: hemangioma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; 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; Prednisolone phosphate
• Other Study ID Numbers: IRB 4502; NIH grant number 10179326