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T he new engl and journa l o f medicine
n engl j med 372;8 february 19, 2015
original article
A Randomized, Controlled Trial of Oral
Propranolol in Infantile Hemangioma
C. Léauté-Labrèze, P. Hoeger, J. Mazereeuw-Hautier, L. Guibaud, E. Baselga,
G. Posiunas, R.J. Phillips, H. Caceres, J.C. Lopez Gutierrez, R. Ballona,
S.F. Friedlander, J. Powell, D. Perek, B. Metz, S. Barbarot, A. Maruani, Z.Z. Szalai,
A. Krol, O. Boccara, R. Foelster-Holst, M.I. Febrer Bosch, J. Su, H. Buckova,
A. Torrelo, F. Cambazard, R. Grantzow, O. Wargon, D. Wyrzykowski, J. Roessler,
J. Bernabeu-Wittel, A.M. Valencia, P. Przewratil, S. Glick, E. Pope, N. Birchall,
L. Benjamin, A.J. Mancini, P. Vabres, P. Souteyrand, I.J. Frieden, C.I. Berul,
C.R. Mehta, S. Prey, F. Boralevi, C.C. Morgan, S. Heritier, A. Delarue, and J.-J. Voisard
The authors’ full names, academic de-
grees, and affiliations are listed in the
Appendix. Address reprint requests to
Dr. Léauté-Labrèze at Unité de Derma-
tologie Pédiatrique, Hôpital Pellegrin-
Enfants, Pl. Amélie Raba Léon, 33 076
Bordeaux CEDEX, France, or at christine
.
A complete list of the investigators who
recruited patients for the trial is provided
in the Supplementary Appendix, available
at .
N Engl J Med 2015;372:735-46.
DOI: 10.1056/NEJMoa1404710
Copyright © 2015 Massachusetts Medical Society.
ABSTR ACT
Background
Oral propranolol has been used to treat complicated infantile hemangiomas, al-
though 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 iden-
tify 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 fail-
ure 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 improve-
ment by week 5, versus 5% of patients who received placebo. A total of 10% of pa-
tients in whom treatment with propranolol was successful required systemic re-
treatment during follow-up. Known adverse events associated with propranolol
(hypoglycemia, hypotension, bradycardia, and bronchospasm) occurred infrequent-
ly, 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.)
Reprinted by permission of N Engl J Med. 2015; 372(8):735-746.
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