Propranolol in Capillary Hemangiomas (HEMANGIOMA)

Double Blind, Randomised, Placebo-controlled Study of Propranolol in Infantile Capillary Hemangiomas

The investigators observed that Propranolol, a beta-blocker commonly used in children was efficient to control the growth of alarming hemangiomas of the face.

The primary objective of this study is to determine the efficiency of 1 month-early treatment of propranolol in infants aged less than 4 months affected by an hemangioma without any consequences on vital or functional structure and not justifying corticosteroids.

The secondary objectives are:

• the kinetic of the hemangioma evolution in infants treated by propranolol
• Observance
• Safety

Study Overview

• Status: Terminated
• Conditions: Hemangioma, Capillary
• Intervention / Treatment: Drug: placebo treatment; Drug: propranolol treatment

Detailed Description

Infantile hemangiomas are frequent vascular tumors (4 à 10 % of the neonates) and correspond to 100 new cases per year in dermatology consultation of the CHU of Bordeaux. Hemangiomas have a characteristic clinical course marked by early proliferation during 3 to 12 months followed by slow and spontaneous involution from 3 to 7 years. Occasionally, as well as esthetical damages, hemangiomas may impair vital structures, ulcerate, bleed, or cause high-output cardiac failure or significant structural abnormalities. Standard treatments (corticotherapy, interferon, vincristine…) lead to a stagnation of hemangiomas in some cases, but with frequent side effects.

We observed that Propranolol, a beta-blocker usually used in neonates could lead to a decreased in volume of serious haemangiomas of the face (article published in New England Journal of Medicine).

In this study, we proposed to determine the efficiency of 1 month-early treatment of propranolol in neonates aged less than 4 months affected by non alarming hemangioma and not justifying corticotherapy. This is a double blind randomized placebo controlled study of propranolol.

Infants will be recruited from the dermatology consultation of CHU Bordeaux. After verification of eligibility criteria and informed consent of legal surrogates, infants will be randomized to receive either propranolol or either placebo. The infants will be observed during 1 month according to the following visits.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33 076
    • Dermatologie pédiatrique

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Infant aged less than 4 months
• Infant with one or more hemangiomas sized more than 1 cm diameter
• Infant not threatening for vital or functional structure and for which no treatment would be proposed
• Informed consent
• Patient with social insurance.

Exclusion Criteria:

• Alarming hemangioma (s) (complicated forms or localization at risk)
• Cardiac pathology (cardiac malformation, heart failure, cardiac arrhythmias, pulmonary hypertension)
• Asthma
• Bronchopulmonary dysplasia
• Bronchiolitis
• Raynaud syndrome
• Phéochromocytoma
• Development of serious form of hemangioma (bleeding, necrosis, ulceration, infection, respiratory distress) requiring standard treatment

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2; 30-days placebo treatment	Drug: placebo treatment; 30 days-placebo treatment : 3 mg/kg 15 days + 4 mg/kg 15 days
Experimental: 1; 30-days propranolol treatment	Drug: propranolol treatment; 30 days-propranolol treatment : 3 mg/kg 15 days + 4 mg/kg 15 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of hemangioma thickness variation measured by ultrasonography from the basal state between the two groups after 1 month-treatment.	30 days treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of hemangioma size variation measured clinically and with photography from the basal state between the two groups after 1 month-treatment.	30 days-treatment
Observance	30 days-treatment

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Investigators: Study Chair: Nicholas Moore, Professor, University Hospital Bordeaux, France

Publications and helpful links

General Publications

• 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.
• Tortoriello TA, Snyder CS, Smith EO, Fenrich AL Jr, Friedman RA, Kertesz NJ. Frequency of recurrence among infants with supraventricular tachycardia and comparison of recurrence rates among those with and without preexcitation and among those with and without response to digoxin and/or propranolol therapy. Am J Cardiol. 2003 Nov 1;92(9):1045-9. doi: 10.1016/j.amjcard.2003.06.002.
• Villain E, Denjoy I, Lupoglazoff JM, Guicheney P, Hainque B, Lucet V, Bonnet D. Low incidence of cardiac events with beta-blocking therapy in children with long QT syndrome. Eur Heart J. 2004 Aug;25(16):1405-11. doi: 10.1016/j.ehj.2004.06.016.
• Kilian K. Hypertension in neonates causes and treatments. J Perinat Neonatal Nurs. 2003 Jan-Mar;17(1):65-74; quiz 75-6. doi: 10.1097/00005237-200301000-00006.
• Fritz KI, Bhat AM. Effect of beta-blockade on symptomatic dexamethasone-induced hypertrophic obstructive cardiomyopathy in premature infants: three case reports and literature review. J Perinatol. 1998 Jan-Feb;18(1):38-44.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: August 28, 2008
• First Submitted That Met QC Criteria: August 28, 2008
• First Posted (Estimate): August 29, 2008

Study Record Updates

• Last Update Posted (Estimate): July 19, 2012
• Last Update Submitted That Met QC Criteria: July 18, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: ultrasonography; propranolol; infantile capillary hemangiomas
• 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; Propranolol
• Other Study ID Numbers: CHUBX 2007/27