Off Label Use of Propranolol for Infancy Hemangiomas

NCT ID: NCT01211080

Last Updated: 2014-11-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

72 participants

Study Classification

OBSERVATIONAL

Study Start Date

2008-08-31

Study Completion Date

2013-10-31

Brief Summary

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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

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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.

Conditions

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Hemangioma

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Threatening hemangioma

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

Intervention Type DRUG

Propranolol 2mg/kg/day divided to three oral doses with or without concomitant physical therapy (cryotherapy, laser)

Interventions

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Propranolol

Propranolol 2mg/kg/day divided to three oral doses with or without concomitant physical therapy (cryotherapy, laser)

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

1 Month

Maximum Eligible Age

8 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hannover Medical School

OTHER

Sponsor Role lead

Responsible Party

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Carsten Engelmann

Oberarzt

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Carsten R Engelmann, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Hannover Medical School

Benno M Ure, Prof.

Role: STUDY_DIRECTOR

Hannover Medical School

Locations

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Pediatric Surgery, Kinderkrankenhaus Bult

Hanover, Hannover, Germany

Site Status

Pediatric Surgery, Hannover Medical School

Hanover, Lower Saxony, Germany

Site Status

Kinderzentrum Klinikum Hildesheim

Hildesheim, Lower Saxony, Germany

Site Status

Countries

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Germany

References

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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.

Reference Type BACKGROUND
PMID: 20644039 (View on PubMed)

Related Links

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Other Identifiers

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AB 3

Identifier Type: -

Identifier Source: org_study_id