Propranolol Versus Prednisolone for Treatment of Symptomatic Hemangiomas

This study has been terminated.
(Serious adverse events with prednisolone, primarily temporary growth retardation, <5th percentile.)
Sponsor:
Information provided by (Responsible Party):
Nancy Bauman, Children's Research Institute
ClinicalTrials.gov Identifier:
NCT00967226
First received: August 26, 2009
Last updated: January 27, 2016
Last verified: January 2016
  Purpose
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 Intervention Phase
Hemangioma of Infancy
Drug: propranolol
Drug: Prednisolone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Propranolol vs Prednisolone for Infant Hemangiomas-A Clinical and Molecular Study

Resource links provided by NLM:


Further study details as provided by Children's Research Institute:

Primary Outcome Measures:
  • Decrease in Size of Hemangioma (Length x Width) in Square mm [ Time Frame: 4-5 months after initiating therapy ] [ Designated as safety issue: No ]
    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:
  • Tolerability of Medication [ Time Frame: enrollment until study close out or withdrawal up to 9 months ] [ Designated as safety issue: Yes ]
    All adverse events relating to medication tolerability including: adrenal crisis, growth/development, constitutional (dehydration), allergy/immunology, dermatologic, endocrine, GI, infection, metabolism/labs, pulmonary, vascular.

  • Number of Serious Adverse Events (SAEs) [ Time Frame: enrollment until study close out or withdrawal up to 9 months ] [ Designated as safety issue: Yes ]
    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.

  • Growth and Development Adverse Events [ Time Frame: enrollment to study withdrawal or close out up to 9 months ] [ Designated as safety issue: No ]
    Number of Growth and Development AEs in each study arm

  • Pulmonary/Respiratory Adverse Events [ Time Frame: enrollment through study close out or withdrawal, up to 9 months ] [ Designated as safety issue: Yes ]
    Number of pulmonary/respiratory adverse events (CTCAE 22) in each study arm

  • Allergy/Immunology Adverse Events [ Time Frame: enrollment through study closeout or study withdrawal up to 9 months ] [ Designated as safety issue: No ]
    Number of allergy/immunology AE per study arm

  • Dermatologic Adverse Events [ Time Frame: enrollment to study close out or withdrawal up to 9 months ] [ Designated as safety issue: No ]
    Number of Dermatologic Adverse Events in each study arm.

  • Endocrinologic Adverse Events [ Time Frame: enrollment to close out or study withdrawal up to 9 months ] [ Designated as safety issue: No ]
    Number of Endocrinologic AEs (of which adrenal crisis does not overlap).

  • Gastrointestinal Adverse Events [ Time Frame: enrollment to study withdrawal or study close out up to 9 months ] [ Designated as safety issue: No ]
    Number of Gastrointestinal AEs in each arm

  • Infectious Adverse Events [ Time Frame: enrollment to study withdrawal or close out up to 9 months ] [ Designated as safety issue: No ]
    Number of infectious AEs in each study arm (i.e. conjunctivitis, thrush, fever)

  • Metabolic or Laboratory AEs [ Time Frame: enrollment to study withdrawal or close out up to 9 months ] [ Designated as safety issue: No ]
    Number of Metabolic or Laboratory AEs in each study arm.

  • Vascular Adverse Events [ Time Frame: enrollment to study withdrawal or close out up to 9 months ] [ Designated as safety issue: No ]
    Number of Vascular AEs in each study arm.

  • Constitutional Adverse Events [ Time Frame: enrollment to study close out or withdrawal up to 9 months ] [ Designated as safety issue: No ]
    Number of constitutional AEs in each study arm.


Enrollment: 19
Study Start Date: July 2009
Study Completion Date: December 2014
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   up to 6 Months   (Child)
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00967226

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

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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 
Study First Received: August 26, 2009
Results First Received: March 14, 2014
Last Updated: January 27, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by 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

ClinicalTrials.gov processed this record on July 26, 2016