Clinical trial NCT01211080: Off Label Use of Propranolol for Infancy Hemangiomas
Official title: Open-label, Uncontrolled Study of the Off Label Use of Propranolol for Infancy Hemangiomas to Identify Side Effects
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hemangioma
Keywords: infancy hemangioma
propranolol
study design
side effects
safety
Lead sponsor: Hannover Medical School
Sponsor class: OTHER
First posted: 2010-09-29
Enrollment: 72
Sex: ALL
Minimum age (years): 1
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Tertiary and Secondary Pediatric Surgery Referral unit Secondary Care Pediatrics Unit

Brief 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.

Eligibility criteria: Inclusion Criteria:

Infants with "problematic" true infantile hemangiomas (potentially disfiguring hemangiomas in the face, functional threatening hemangiomas of hands, feet, genitalia)\> 4 weeks and \< 8 months of age.

Exclusion Criteria:

"Uncomplicated" Hemangiomas (trunk, extremities), infants with heart disease, known arrhythmias, bronchoobstructive disease, known hypoglycaemia events.

Primary outcomes:
measure: Cosmesis of the lesion and surrounding skin
timeFrame: Completed 8 months of life
measure: Side effects
timeFrame: Completed 8th month of life
Secondary outcomes:
measure: hemangioma size
timeFrame: completed 8 th month of life
Other outcomes:
Locations:
city: Hannover
country: Germany
facility: Pediatric Surgery, Hannover Medical School
state: Lower Saxony
city: Hildesheim
country: Germany
facility: Kinderzentrum Klinikum Hildesheim
state: Lower Saxony
city: Hannover
country: Germany
facility: Pediatric Surgery, Kinderkrankenhaus Bult
Study officials:
affiliation: Hannover Medical School
name: Carsten R Engelmann, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hannover Medical School
name: Benno M Ure, Prof.
role: STUDY_DIRECTOR
References:
citation: Holland KE, Frieden IJ, Frommelt PC, Mancini AJ, Wyatt D, Drolet BA. Hypoglycemia in children taking propranolol for the treatment of infantile hemangioma. Arch Dermatol. 2010 Jul;146(7):775-8. doi: 10.1001/archdermatol.2010.158.