Efficacy and Safety of Propranolol Versus Acebutolol on the Proliferative Phase of Infantile Hemangioma

There is no effective treatment for hemangioma regardless of immediate severity. That is in this respect a orphan disease. These hemangiomas, sometimes large, will have a phase of proliferation of several months (very scary for parents) and regression over several years. The natural history is peppered with local complications (ulcers) and aesthetic and psychological sequelae (sometimes major for the child and the family). The effects of acebutolol and propranolol on the proliferative hemangiomas were discovered accidentally by two French teams (Montpellier for acebutolol and Bordeaux for propranolol). Acebutolol and propranolol have been used for many years for the treatment of hypertension and congenital heart disease, including infants, with few side effects. The effects of acebutolol and propranolol were immediately visible with reduced volume and skin whitening of the hemangioma. In a preliminary study, acebutolol was administered to 20 patients in Montpellier with big regression of hemangiomas. The aim of the study was to compare the clinical efficacy of acebutolol (10mg/Kg/jour) and propranolol (3mg/Kg/j) on the proliferative phase of infantile hemangioma in infants.

Study Overview

• Status: Terminated
• Conditions: Hemangioma
• Intervention / Treatment: Drug: Propanolol; Drug: Acebutolol

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69130
    • UH Lyon
  • Marseille, France, 13385
    • UH Marseill
  • Montpellier, France, 34295
    • Chirurgy Plastic Department
  • Nîmes, France, 30000
    • UH NCaremeau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Infants under 6 months

• Presenting a hemangioma with the following characteristics:

  • subcutaneous and / or cutaneous
  • minimum diameter of 1.5cm on face, 5cm outside face and 3cm if it is ulcerated.
  • without functional impairment requiring treatment or vital corticosteroid
• Consent of both parents (or the person having parental authority in families)
• Which at least one parent is a beneficiary of a social security system.

Exclusion Criteria:

• Indication of treatment with corticosteroids for an indication other than hemangioma
• Indication of treatment with beta-blocker for another indication that the hemangioma

• Infant presenting cons-indications for the administration of acebutolol or propranolol:

  • Asthma and chronic obstructive pulmonary disease in their severe forms.
  • Heart failure controlled by treatment.
  • Cardiogenic shock
  • Prinzmetal Angina
  • Bradycardia (<80 beats / min at rest the first month <70/minute from 1 to 6 month).
  • Raynaud's phenomenon and peripheral arterial disorders in their severe forms.
  • Pheochromocytoma untreated.
  • Low blood pressure (blood pressure <60/30 mmHg before 6 months)
  • Hypersensitivity to acebutolol or propranolol
  • History of anaphylactic reaction.
  • Treatment with amiodarone and / or calcium channel blockers.
  • Congenital heart disease outside inter auricular communication (CIA) or inter ventricular communication (CIV) insignificant

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
Active Comparator: propanolol; Propanolol (Syprol:oral solution)	Drug: Propanolol; 3 mg/kg/jour in 3 doses during 90 days after gradual increase of doses in the first week; Other Names: Syprol
Active Comparator: Acebutolol; Acebutolol (Sectral:oral solution)	Drug: Acebutolol; 10 mg/kg/jour in 2 doses during 90 days after gradual increase of doses in the first week; Other Names: Sectral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemangioma size	It will be evaluated using a VAS (visual analogue scale) on a series of photos at Day 0, Day 30 and Day 90	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerance of treatment	All adverse events are collected at each visited	3 months
Proportion of patients requiring treatment with corticosteroids because of the evolution of a 'serious' hemangioma		3 months

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Principal Investigator: Michèle Bigorre, PH, UH Montpellier

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: November 28, 2012
• First Submitted That Met QC Criteria: December 4, 2012
• First Posted (Estimate): December 6, 2012

Study Record Updates

• Last Update Posted (Estimate): June 1, 2016
• Last Update Submitted That Met QC Criteria: May 31, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Propranolol; Infants; Hemangioma; Acebutolol; Beta-blocker
• 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; Autonomic Agents; Peripheral Nervous System Agents; Sympathomimetics; Adrenergic beta-1 Receptor Antagonists; Propranolol; Acebutolol
• Other Study ID Numbers: 8638