Off Label Use of Propranolol for Infancy Hemangiomas (PIHS)
|ClinicalTrials.gov Identifier: NCT01211080|
Recruitment Status : Completed
First Posted : September 29, 2010
Last Update Posted : November 11, 2014
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.
|Condition or disease||Intervention/treatment|
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.
|Study Type :||Observational|
|Actual Enrollment :||72 participants|
|Official Title:||Open-label, Uncontrolled Study of the Off Label Use of Propranolol for Infancy Hemangiomas to Identify Side Effects|
|Study Start Date :||August 2008|
|Actual Primary Completion Date :||October 2013|
|Actual Study Completion Date :||October 2013|
The group with cosmetically threatening of functionally threatening hemangiomas warranting active treatment according to our usual criteria (location face, hands, feet with a strong growth tendency and below age of 8 months)
Propranolol 2mg/kg/day divided to three oral doses with or without concomitant physical therapy (cryotherapy, laser)
- Cosmesis of the lesion and surrounding skin [ Time Frame: Completed 8 months of life ]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.
- Side effects [ Time Frame: Completed 8th month of life ]Number of Participants with Adverse Events in the cardiovascular, bronchopulmonary and metabolic system as a Measure of Safety and Tolerability
- hemangioma size [ Time Frame: completed 8 th month of life ]Size is measured with calipers and ultrasound
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01211080
|Pediatric Surgery, Hannover Medical School|
|Hannover, Lower Saxony, Germany, 30625|
|Kinderzentrum Klinikum Hildesheim|
|Hildesheim, Lower Saxony, Germany, 31134|
|Pediatric Surgery, Kinderkrankenhaus Bult|
|Hannover, Germany, 30173|
|Principal Investigator:||Carsten R Engelmann, MD PhD||Hannover Medical School|
|Study Director:||Benno M Ure, Prof.||Hannover Medical School|