Off Label Use of Propranolol for Infancy Hemangiomas (PIHS)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2012 by Hannover Medical School.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by (Responsible Party):
Carsten Engelmann, Hannover Medical School
ClinicalTrials.gov Identifier:
NCT01211080
First received: September 28, 2010
Last updated: September 12, 2012
Last verified: September 2012
  Purpose

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 Intervention
Hemangioma
Drug: Propranolol

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Open-label, Uncontrolled Study of the Off Label Use of Propranolol for Infancy Hemangiomas to Identify Side Effects

Resource links provided by NLM:


Further study details as provided by Hannover Medical School:

Primary Outcome Measures:
  • Cosmesis of the lesion and surrounding skin [ Time Frame: Completed 8 months of life ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Number of Participants with Adverse Events in the cardiovascular, bronchopulmonary and metabolic system as a Measure of Safety and Tolerability


Secondary Outcome Measures:
  • hemangioma size [ Time Frame: completed 8 th month of life ] [ Designated as safety issue: No ]
    Size is measured with calipers and ultrasound


Enrollment: 72
Study Start Date: August 2008
Estimated Study Completion Date: December 2012
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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)
Drug: Propranolol
Propranolol 2mg/kg/day divided to three oral doses with or without concomitant physical therapy (cryotherapy, laser)

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

Ages Eligible for Study:   1 Month to 8 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Tertiary and Secondary Pediatric Surgery Referral unit Secondary Care Pediatrics Unit

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01211080

Locations
Germany
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
Sponsors and Collaborators
Hannover Medical School
Investigators
Principal Investigator: Carsten R Engelmann, MD PhD Hannover Medical School
Study Director: Benno M Ure, Prof. Hannover Medical School
  More Information

Additional Information:
Publications:
Responsible Party: Carsten Engelmann, Oberarzt, Hannover Medical School
ClinicalTrials.gov Identifier: NCT01211080     History of Changes
Other Study ID Numbers: AB 3
Study First Received: September 28, 2010
Last Updated: September 12, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Germany:Bezirksregierung Hannover, Lower Saxony

Keywords provided by Hannover Medical School:
infancy hemangioma
propranolol
study design
side effects
safety

Additional relevant MeSH terms:
Hemangioma
Neoplasms, Vascular Tissue
Neoplasms by Histologic Type
Neoplasms
Propranolol
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Antihypertensive Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on September 11, 2014