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Importance: 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., Objectives: 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., Design, Setting, and Participants: 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., Interventions: Treatment with oral propranolol vs prednisolone (2.0 mg/kg/d) until halted owing to toxic effects or clinical response., Main Outcomes and Measures: 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 and Relevance: 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.

Objectives: We sought to determine the effect of propranolol on cardiovascular and blood glucose parameters in infants with symptomatic infantile hemangiomas who were hospitalized for initiation of treatment, and to analyze adverse effects of propranolol throughout the course of inpatient and outpatient treatment., Methods: A retrospective cohort analysis was performed on 50 infants (age less than 12 months) with symptomatic infantile hemangiomas who were hospitalized for propranolol initiation between 2008 and 2012. Demographic data and disease characteristics were recorded. Systolic and diastolic blood pressures, heart rate, blood glucose values, and adverse events recorded during hospitalization were analyzed. An additional cohort of 200 consecutively treated children was also assessed for adverse events associated with outpatient propranolol use., Results: The median age among the inpatient cohort was 3.4 months (range, 0.8 to 12.0 months). Infants older than 6 months were more likely to exhibit bradycardia than were younger infants (p < 0.001). Hypotensive and/or bradycardic periods were infrequent and were not associated with observable clinical symptoms. The mean systolic and diastolic blood pressures and the mean heart rate decreased significantly from day 1 of hospitalization to day 2 (p = 0.004; p = 0.008; p < 0.001), but not from day 2 to day 3, when the propranolol dose was increased to target. Hypoglycemia was rare (0.3% incidence.) Among the 250 outpatients, 2 infants developed lethargy and hypoglycemia during a viral illness and recovered without sequelae. One infant experienced recurrent bronchospasm with viral illnesses and required concomitant bronchodilator therapy., Conclusions: Frequent deviations from normal ranges of blood pressure and heart rate occur upon initiation of propranolol, but are clinically asymptomatic. These findings support that outpatient initiation of propranolol in healthy, normotensive infants appears to be a relatively safe alternative to inpatient initiation. Hypoglycemia is rare, but can occur throughout the treatment period; parent counseling is of paramount importance.

Infantile hemangiomas (IHs) are common neoplasms composed of proliferating endothelial-like cells. Despite the relative frequency of IH and the potential severity of complications, there are currently no uniform guidelines for treatment. Although propranolol has rapidly been adopted, there is significant uncertainty and divergence of opinion regarding safety monitoring, dose escalation, and its use in PHACE syndrome (PHACE = posterior fossa, hemangioma, arterial lesions, cardiac abnormalities, eye abnormalities; a cutaneous neurovascular syndrome characterized by large, segmental hemangiomas of the head and neck along with congenital anomalies of the brain, heart, eyes and/or chest wall). A consensus conference was held on December 9, 2011. The multidisciplinary team reviewed existing data on the pharmacologic properties of propranolol and all published reports pertaining to the use of propranolol in pediatric patients. Workgroups were assigned specific topics to propose protocols on the following subjects: contraindications, special populations, pretreatment evaluation, dose escalation, and monitoring. Consensus protocols were recorded during the meeting and refined after the meeting. When appropriate, protocol clarifications and revision were made and agreed upon by the group via teleconference. Because of the absence of high-quality clinical research data, evidence-based recommendations are not possible at present. However, the team agreed on a number of recommendations that arose from a review of existing evidence, including when to treat complicated IH; contraindications and pretreatment evaluation protocols; propranolol use in PHACE syndrome; formulation, target dose, and frequency of propranolol; initiation of propranolol in infants; cardiovascular monitoring; ongoing monitoring; and prevention of hypoglycemia. Where there was considerable controversy, the more conservative approach was selected. We acknowledge that the recommendations are conservative in nature and anticipate that they will be revised as more data are made available.

Objectives: Our primary objective was to review the current use of propranolol for treatment of infantile hemangioma (IH), specifically regarding 1) the age at initiation of therapy, 2) the method of initiation, 3) the use of other adjuvant therapy, 4) the duration of therapy and relapse rate, 5) the adverse events, and 6) the outcome. Our secondary objective was to describe a randomized, controlled, single-blinded trial comparing propranolol to prednisolone for treatment of IH., Methods: Ovid Medline and PubMed searches were completed for the MeSH keywords "propranolol" and "hemangioma." Forty-nine English-language articles were published between June 2008 and September 2010, and 28 of these reported data from a total of 213 patients. Only 6 studies treated more than 10 patients, and these were selected for review in detail (154 patients)., Results: The treatment was initiated during infancy in 92.9% of patients (mean, 4.5 months). Sixty-five percent of patients were treated with 2 mg/kg per day, and 25.3% with 3 mg/kg per day. Patients were monitored overnight at initiation of treatment in 3 series (59 patients), for 4 to 6 hours as outpatients in 2 series (62 patients), and initially as inpatients but later as outpatients in 1 series (32 patients). Propranolol was used as sole therapy in about two thirds of patients (103 patients). Treatment was ongoing in 46% of patients at the time of publication. The average treatment duration in the remaining patients was 5.1 months. Rebound growth occurred in 21% of patients after a mean of 4.3 months of therapy. Adverse events occurred in 18.1% of patients and included hypotension in 6, somnolence in 6, wheezing in 4, insomnia, agitation, and/or nightmares in 6, cool hands or night sweats in 2, gastroesophageal reflux in 3, and psoriasis-like rash in 1. All authors reported a favorable outcome with propranolol, but the definition of efficacy was not standardized., Conclusions: Propranolol is an attractive alternative to other treatments for IH. Despite apparent widespread use of this medication, the data are limited, and prospective studies are lacking for this indication. The relatively high rate of adverse effects supports the need for careful monitoring of patients on this therapy. Fastidious reporting of adverse events and objective evaluation of early and late outcomes are necessary to improve our understanding of the use of propranolol for this indication.