title: A randomized, controlled trial of oral propranolol in infantile hemangioma.
abstract: BACKGROUND
  Oral propranolol has been used to treat complicated infantile hemangiomas, although data from randomized, controlled trials to inform its use are limited.
  
  
  METHODS
  We performed a multicenter, randomized, double-blind, adaptive, phase 2-3 trial assessing the efficacy and safety of a pediatric-specific oral propranolol solution in infants 1 to 5 months of age with proliferating infantile hemangioma requiring systemic therapy. Infants were randomly assigned to receive placebo or one of four propranolol regimens (1 or 3 mg of propranolol base per kilogram of body weight per day for 3 or 6 months). A preplanned interim analysis was conducted to identify the regimen to study for the final efficacy analysis. The primary end point was success (complete or nearly complete resolution of the target hemangioma) or failure of trial treatment at week 24, as assessed by independent, centralized, blinded evaluations of standardized photographs.
  
  
  RESULTS
  Of 460 infants who underwent randomization, 456 received treatment. On the basis of an interim analysis of the first 188 patients who completed 24 weeks of trial treatment, the regimen of 3 mg of propranolol per kilogram per day for 6 months was selected for the final efficacy analysis. The frequency of successful treatment was higher with this regimen than with placebo (60% vs. 4%, P<0.001). A total of 88% of patients who received the selected propranolol regimen showed improvement by week 5, versus 5% of patients who received placebo. A total of 10% of patients in whom treatment with propranolol was successful required systemic retreatment during follow-up. Known adverse events associated with propranolol (hypoglycemia, hypotension, bradycardia, and bronchospasm) occurred infrequently, with no significant difference in frequency between the placebo group and the groups receiving propranolol.
  
  
  CONCLUSIONS
  This trial showed that propranolol was effective at a dose of 3 mg per kilogram per day for 6 months in the treatment of infantile hemangioma. (Funded by Pierre Fabre Dermatologie; ClinicalTrials.gov number, NCT01056341.).
authors.affiliation: The authors' affiliations are listed in the Appendix.
authors.forename: Christine
authors.initials: C
authors.lastname: Léauté-Labrèze
authors.forename: Peter
authors.initials: P
authors.lastname: Hoeger
authors.forename: Juliette
authors.initials: J
authors.lastname: Mazereeuw-Hautier
authors.forename: Laurent
authors.initials: L
authors.lastname: Guibaud
authors.forename: Eulalia
authors.initials: E
authors.lastname: Baselga
authors.forename: Gintas
authors.initials: G
authors.lastname: Posiunas
authors.forename: Roderic J
authors.initials: RJ
authors.lastname: Phillips
authors.forename: Hector
authors.initials: H
authors.lastname: Caceres
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Lopez Gutierrez
authors.forename: Rosalia
authors.initials: R
authors.lastname: Ballona
authors.forename: Sheila Fallon
authors.initials: SF
authors.lastname: Friedlander
authors.forename: Julie
authors.initials: J
authors.lastname: Powell
authors.forename: Danuta
authors.initials: D
authors.lastname: Perek
authors.forename: Brandie
authors.initials: B
authors.lastname: Metz
authors.forename: Sebastien
authors.initials: S
authors.lastname: Barbarot
authors.forename: Annabel
authors.initials: A
authors.lastname: Maruani
authors.forename: Zsuzsanna Zsofia
authors.initials: ZZ
authors.lastname: Szalai
authors.forename: Alfons
authors.initials: A
authors.lastname: Krol
authors.forename: Olivia
authors.initials: O
authors.lastname: Boccara
authors.forename: Regina
authors.initials: R
authors.lastname: Foelster-Holst
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Febrer Bosch
authors.forename: John
authors.initials: J
authors.lastname: Su
authors.forename: Hana
authors.initials: H
authors.lastname: Buckova
authors.forename: Antonio
authors.initials: A
authors.lastname: Torrelo
authors.forename: Frederic
authors.initials: F
authors.lastname: Cambazard
authors.forename: Rainer
authors.initials: R
authors.lastname: Grantzow
authors.forename: Orli
authors.initials: O
authors.lastname: Wargon
authors.forename: Dariusz
authors.initials: D
authors.lastname: Wyrzykowski
authors.forename: Jochen
authors.initials: J
authors.lastname: Roessler
authors.forename: Jose
authors.initials: J
authors.lastname: Bernabeu-Wittel
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Valencia
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Przewratil
authors.forename: Sharon
authors.initials: S
authors.lastname: Glick
authors.forename: Elena
authors.initials: E
authors.lastname: Pope
authors.forename: Nicholas
authors.initials: N
authors.lastname: Birchall
authors.forename: Latanya
authors.initials: L
authors.lastname: Benjamin
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Mancini
authors.forename: Pierre
authors.initials: P
authors.lastname: Vabres
authors.forename: Pierre
authors.initials: P
authors.lastname: Souteyrand
authors.forename: Ilona J
authors.initials: IJ
authors.lastname: Frieden
authors.forename: Charles I
authors.initials: CI
authors.lastname: Berul
authors.forename: Cyrus R
authors.initials: CR
authors.lastname: Mehta
authors.forename: Sorilla
authors.initials: S
authors.lastname: Prey
authors.forename: Franck
authors.initials: F
authors.lastname: Boralevi
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Morgan
authors.forename: Stephane
authors.initials: S
authors.lastname: Heritier
authors.forename: Alain
authors.initials: A
authors.lastname: Delarue
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Voisard
mesh_terms: D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006391:Hemangioma / Q000188:drug therapy*; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007223:Infant; D008297:Male; D011433:Propranolol / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D011433:Propranolol