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Reprinted by permission of N Engl J Med. 2015; 372(8):735-746.

T he new engl and journa l o f medicine

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 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.) ABSTR ACT

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 .labreze@chu-bordeaux.fr. A complete list of the investigators who recruited patients for the trial is provided in the Supplementary Appendix, available at NEJM.org. N Engl J Med 2015;372:735-46. DOI: 10.1056/NEJMoa1404710 Copyright © 2015 Massachusetts Medical Society.

n engl j med 372;8  nejm.org february 19 , 2015

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