title: Propranolol vs prednisolone for symptomatic proliferating infantile hemangiomas: a randomized clinical trial.
abstract: OBJECTIVE
  While propranolol is touted as superior to prednisolone for treating infantile hemangiomas (IH), a randomized clinical trial (RCT) comparing the outcome and tolerability of these medications for symptomatic, proliferating IH has not been reported.
  
  
  OBJECTIVE
  To determine if oral propranolol is more efficacious and better tolerated than prednisolone in treating symptomatic, proliferating IH and to determine the feasibility of conducting a multi-institutional, RCT comparing efficacy and tolerability of both medications.
  
  
  METHODS
  Phase 2, investigator-blinded, multi-institutional RCT conducted in 3 academic vascular anomalies clinics on 19 of 44 eligible infants aged between 2 weeks and 6 months. All participating patients had symptomatic proliferating IH treated between September 1, 2010, and August 1, 2012.
  
  
  METHODS
  Treatment with oral propranolol vs prednisolone (2.0 mg/kg/d) until halted owing to toxic effects or clinical response.
  
  
  METHODS
  Primary outcome was change in IH size after 4 months of therapy. Secondary outcomes were response rate and frequency and severity of adverse events (AEs).
  
  
  RESULTS
  The primary outcome showed no difference in lesion size or affected skin area after 4 months of therapy: 41% and 1.32 mm2 for prednisolone vs 64% and 0.55 mm2 for propranolol (P = .12 for lesion size, and P = .56 for affected skin area). Longitudinal analyses showed a faster response in total lesion outer dimension with prednisolone (P = .03), but this advantage over time was not noted when central clearing and outer dimension were included in the analysis (P = .91). The overall frequency of AEs was similar (44 for prednisolone vs 32 for propranolol) (P = .84), but prednisolone-treated participants had more grade 3 severe AEs (11 vs 1) (P = .01), particularly growth retardation resulting in size and weight below the fifth percentile. Early study withdrawal owing to AEs occurred in 6 (75%) of 8 patients in the prednisolone group but 0 of 11 propranolol-treated participants. The mean duration of therapy was shorter for prednisolone (141 vs 265 days), reflecting the higher rate of early withdrawals.
  
  
  CONCLUSIONS
  Both medications show similar efficacy for reducing the area of symptomatic, proliferating IH. Although prednisolone showed a faster response rate, propranolol was better tolerated with significantly fewer severe AEs. Propranolol should be the first line of therapy for symptomatic IH unless contraindicated or unless future studies demonstrate severe AEs from propranolol. Recruiting participants for a phase 3 RCT would be difficult owing to safety profiles measured here and emerging trends favoring propranolol. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00967226.
authors: Department of Otolaryngology, Children's National Medical Center, Washington, DC.
authors: Nancy M
authors: NM
authors: Bauman
authors: Department of Biostatistics, Children's National Medical Center, Washington, DC.
authors: Robert J
authors: RJ
authors: McCarter
authors: Department of General Surgery, Children's National Medical Center, Washington, DC.
authors: Philip C
authors: PC
authors: Guzzetta
authors: Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts.
authors: Jennifer J
authors: JJ
authors: Shin
authors: Department of Plastic Surgery, Children's National Medical Center, Washington, DC.
authors: Albert K
authors: AK
authors: Oh
authors: Department of Otolaryngology, Children's National Medical Center, Washington, DC.
authors: Diego A
authors: DA
authors: Preciado
authors: Department of Biostatistics, Children's National Medical Center, Washington, DC.
authors: Jianping
authors: J
authors: He
authors: Department of Cardiology, Children's National Medical Center, Washington, DC.
authors: Elizabeth Anne
authors: EA
authors: Greene
authors: Department of Dermatology, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors: Katherine B
authors: KB
authors: Puttgen
mesh_terms: D000284:Administration, Oral; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006391:Hemangioma / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use*; D011433:Propranolol / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014665:Vasodilator Agents; D011239:Prednisolone; D011433:Propranolol