Off Label Use of Propranolol for Infancy Hemangiomas
Condition: Hemangioma
MeSH terms: Hemangioma
Study type: Observational

Summary: 
      Propranolol use for infancy hemangiomas is of world wide interest due to low cost and
      presumed efficacy. The investigators hypothesized that the drug ist highly active against
      growing hemangiomas in problematic sites and that there are little side effects.

      This observational study was undertaken in an uncontrolled fashion to determine sample size,
      design and and tools for a later randomized controlled trial on propranolol versus physical
      therapy (i.e.cryotherapy) which is the most prevalent treatment for the condition. During
      this initial series side effects and relevant design aspects became evident which warrant
      expedited reporting.
    

Detailed description: 
      Treatment modalities: The investigators employed the "best-guess"-dose from the literature at
      2 mg/kg/day divided into three daily oral administrations. Individualized capsules were
      manufactured from Propranolol tablets by the hospital pharmacies and dissolved in sweetened
      tea before use. Treatment was started at 1mg/kg/day and routinely increased after 24 hrs. or
      later when three subsequent doses had been tolerated without bradycardia (< 70 bpm when
      sleeping) or other unwanted events. No other medical treatment was admitted. Physical
      treatment (cryotherapy, interstitial laser) was administered in parallel to propranolol in 16
      patients with threatening hemangiomas (severe impediments to function or cosmesis requiring
      immediate reduction).

      Surveillance and adverse event (AE) reporting:

      Pretreatment monitoring included a 24 hr ECG (in KKB a 2 minute rhythm strip), pulse, blood
      pressure, fasting blood glucose and echocardiography. All patients were kept at a cardiac
      monitor. Blood pressure was monitored 6 hourly and blood glucose was assayed twice with each
      new dose at one hour after drug ingestion. If the patient has had 3 full doses the
      investigators repeated the 24 hr ECG and the echocardiography. Bradycardia and Hypotension
      events were defined according to the age dependent standards , Side effects/adverse events
      were defined according to ICH guidelines and screened for as events leading to either a
      physician contract and a medical measure (dose reduction, ß-mimetic or other medication).

      Lesion evaluation:

      Hemangioma size was measured with calipers before and after the completed therapy at the end
      of the 8th month of life. Thickness was checked with a 7.5 mHz linear array pediatric probe.

      For evaluation of their cosmesis the lesions were documented with 2 photos each (white
      balanced flash and ambiance light) before and after treatment (standardized to 30 cm
      distance, circa 2 Mb resolution). Images were shown at the same week to 3 examiners being
      unaware whether images were taken pre- or post treatment. This was repeated twice at two
      weeks interval. As there is no validated hemangioma specific assessment tool a rating form
      was compiled in an expert discussion from validated scar and burns scales: Categorical items
      included "Vascularity" and "Height" from the Vancouver Scar Scale , "Irregularity" from the
      Hamilton burn scar rating form for photographic analysis and the "matte/shiny" classification
      from the Manchester Scar Scale . A 10 cm plastic surgery visual analogue scale provided
      non-categorical data on overall appearance.
    

Intervention name(s): Propranolol
Intervention type(s): Drug
Intervention description(s): Propranolol 2mg/kg/day divided to three oral doses with or without concomitant physical therapy (cryotherapy, laser)
Intervention MeSH terms: Propranolol
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Tertiary and Secondary Pediatric Surgery Referral unit Secondary Care Pediatrics Unit
      
Keywords: infancy hemangioma; propranolol; study design; side effects; safety