A randomized, controlled trial of oral propranolol in infantile hemangioma
Christine Léauté-Labrèze, Peter Hoeger, Juliette Mazereeuw-Hautier, Laurent Guibaud, Eulalia Baselga, Gintas Posiunas, Roderic J Phillips, Hector Caceres, Juan Carlos Lopez Gutierrez, Rosalia Ballona, Sheila Fallon Friedlander, Julie Powell, Danuta Perek, Brandie Metz, Sebastien Barbarot, Annabel Maruani, Zsuzsanna Zsofia Szalai, Alfons Krol, Olivia Boccara, Regina Foelster-Holst, Maria Isabel Febrer Bosch, John Su, Hana Buckova, Antonio Torrelo, Frederic Cambazard, Rainer Grantzow, Orli Wargon, Dariusz Wyrzykowski, Jochen Roessler, Jose Bernabeu-Wittel, Adriana M Valencia, Przemyslaw Przewratil, Sharon Glick, Elena Pope, Nicholas Birchall, Latanya Benjamin, Anthony J Mancini, Pierre Vabres, Pierre Souteyrand, Ilona J Frieden, Charles I Berul, Cyrus R Mehta, Sorilla Prey, Franck Boralevi, Caroline C Morgan, Stephane Heritier, Alain Delarue, Jean-Jacques Voisard, Christine Léauté-Labrèze, Peter Hoeger, Juliette Mazereeuw-Hautier, Laurent Guibaud, Eulalia Baselga, Gintas Posiunas, Roderic J Phillips, Hector Caceres, Juan Carlos Lopez Gutierrez, Rosalia Ballona, Sheila Fallon Friedlander, Julie Powell, Danuta Perek, Brandie Metz, Sebastien Barbarot, Annabel Maruani, Zsuzsanna Zsofia Szalai, Alfons Krol, Olivia Boccara, Regina Foelster-Holst, Maria Isabel Febrer Bosch, John Su, Hana Buckova, Antonio Torrelo, Frederic Cambazard, Rainer Grantzow, Orli Wargon, Dariusz Wyrzykowski, Jochen Roessler, Jose Bernabeu-Wittel, Adriana M Valencia, Przemyslaw Przewratil, Sharon Glick, Elena Pope, Nicholas Birchall, Latanya Benjamin, Anthony J Mancini, Pierre Vabres, Pierre Souteyrand, Ilona J Frieden, Charles I Berul, Cyrus R Mehta, Sorilla Prey, Franck Boralevi, Caroline C Morgan, Stephane Heritier, Alain Delarue, Jean-Jacques Voisard
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.).
Source: PubMed