Propranolol Versus Prednisolone for Treatment of Symptomatic Hemangiomas

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hemangioma of Infancy	Drug: propranolol; Drug: Prednisolone	Phase 2

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	19 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Propranolol vs Prednisolone for Infant Hemangiomas-A Clinical and Molecular Study
Study Start Date :	July 2009
Actual Primary Completion Date :	January 2013
Actual Study Completion Date :	December 2014

Arms and Interventions

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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 Name: pediapred

Outcome Measures

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Primary Outcome Measures :

1. Decrease in Size of Hemangioma (Length x Width) in Square mm [ Time Frame: 4-5 months after initiating therapy ]
   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.

Secondary Outcome Measures :

1. Tolerability of Medication [ Time Frame: enrollment until study close out or withdrawal up to 9 months ]
   All adverse events relating to medication tolerability including: adrenal crisis, growth/development, constitutional (dehydration), allergy/immunology, dermatologic, endocrine, GI, infection, metabolism/labs, pulmonary, vascular.
2. Number of Serious Adverse Events (SAEs) [ Time Frame: enrollment until study close out or withdrawal up to 9 months ]
   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.
3. Growth and Development Adverse Events [ Time Frame: enrollment to study withdrawal or close out up to 9 months ]
   Number of Growth and Development AEs in each study arm
4. Pulmonary/Respiratory Adverse Events [ Time Frame: enrollment through study close out or withdrawal, up to 9 months ]
   Number of pulmonary/respiratory adverse events (CTCAE 22) in each study arm
5. Allergy/Immunology Adverse Events [ Time Frame: enrollment through study closeout or study withdrawal up to 9 months ]
   Number of allergy/immunology AE per study arm
6. Dermatologic Adverse Events [ Time Frame: enrollment to study close out or withdrawal up to 9 months ]
   Number of Dermatologic Adverse Events in each study arm.
7. Endocrinologic Adverse Events [ Time Frame: enrollment to close out or study withdrawal up to 9 months ]
   Number of Endocrinologic AEs (of which adrenal crisis does not overlap).
8. Gastrointestinal Adverse Events [ Time Frame: enrollment to study withdrawal or study close out up to 9 months ]
   Number of Gastrointestinal AEs in each arm
9. Infectious Adverse Events [ Time Frame: enrollment to study withdrawal or close out up to 9 months ]
   Number of infectious AEs in each study arm (i.e. conjunctivitis, thrush, fever)
10. Metabolic or Laboratory AEs [ Time Frame: enrollment to study withdrawal or close out up to 9 months ]
    Number of Metabolic or Laboratory AEs in each study arm.
11. Vascular Adverse Events [ Time Frame: enrollment to study withdrawal or close out up to 9 months ]
    Number of Vascular AEs in each study arm.
12. Constitutional Adverse Events [ Time Frame: enrollment to study close out or withdrawal up to 9 months ]
    Number of constitutional AEs in each study arm.

Eligibility Criteria

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Ages Eligible for Study:	up to 6 Months (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• infants with symptomatic hemangiomas

Exclusion Criteria:

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

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

Sponsors and Collaborators

Nancy Bauman

Investigators

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

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

Pérez RS, Mora PC, Rodríguez JD, Sánchez 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. 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.

Léauté-Labrèze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Taïeb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008 Jun 12;358(24):2649-51. doi: 10.1056/NEJMc0708819.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Review.

Responsible Party:	Nancy Bauman, Professor, George Washington University, Attending Children;s National, Children's Research Institute
ClinicalTrials.gov Identifier:	NCT00967226 History of Changes
Other Study ID Numbers:	IRB 4502; NIH grant number 10179326
First Posted:	August 27, 2009
Results First Posted:	February 24, 2016
Last Update Posted:	February 24, 2016
Last Verified:	January 2016

Keywords provided by Nancy Bauman, Children's Research Institute:

hemangioma

Additional relevant MeSH terms:

Hemangioma; Neoplasms, Vascular Tissue; Neoplasms by Histologic Type; Neoplasms; Prednisolone acetate; Methylprednisolone acetate; Prednisolone; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone hemisuccinate; Prednisolone phosphate; Propranolol; Anti-Inflammatory Agents; Glucocorticoids; Hormones

Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Neuroprotective Agents; Protective Agents; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action