Open-label, Uncontrolled Study of the Off Label Use of Propranolol for Infancy Hemangiomas to Identify Side Effects
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).
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.
Observational Model: Cohort, Time Perspective: Prospective
Cosmesis of the lesion and surrounding skin
Post treatment cosmetic and defiguration result with a hemangioma specific rating tool for categorical (color, vascularity, height, matte/shiny) and non-categorical data (visual analogue scale for overall appearance) from the Vancouver Burn Scar Scale, the Manchester Scar Scale and the Hamilton Burn scar scale by 3 examiners.
Completed 8 months of life
Carsten R Engelmann, MD PhD
Hannover Medical School
Germany: Federal Institute for Drugs and Medical Devices