HemangiomaPIHSNCT01211080
Off Label Use of Propranolol for Infancy Hemangiomas
An observational study of Hemangioma, run by Hannover Medical School at 3 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 month to 8 months
- Conditions the study is for
- Hemangioma
- What is being tested?
- Propranolol
- Type of treatment
- Pill or oral medicine
- How many people
- 72 participants
- Where
- 3 sitesGermany
- Study dates
- Aug 2008to Oct 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 8 months
- All sexes
- No healthy volunteers
- Child
Study population: Tertiary and Secondary Pediatric Surgery Referral unit Secondary Care Pediatrics Unit
Who may be able to join
- 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.
Who cannot join
- "Uncomplicated" Hemangiomas (trunk, extremities), infants with heart disease, known arrhythmias, bronchoobstructive disease, known hypoglycaemia events.
Trial locations and contacts
3 sites in 1 country.
Germany3 sites
Pediatric Surgery, Kinderkrankenhaus Bult
Hanover, Hannover, 30173
Pediatric Surgery, Hannover Medical School
Hanover, Lower Saxony, 30625
Kinderzentrum Klinikum Hildesheim
Hildesheim, Lower Saxony, 31134
About this study
Official title: Open-label, Uncontrolled Study of the Off Label Use of Propranolol for Infancy Hemangiomas to Identify Side Effects
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.
Read the 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.
- Conditions
- Hemangioma
- Being tested
- Propranolol
- Keywords
- infancy hemangioma, propranolol, study design, side effects, safety
- Medical subject headings
- Hemangioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropranololDrug
Propranolol 2mg/kg/day divided to three oral doses with or without concomitant physical therapy (cryotherapy, laser)
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Drug: Propranolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Completed 8 months of life
Side effects
Number of Participants with Adverse Events in the cardiovascular, bronchopulmonary and metabolic system as a Measure of Safety and Tolerability
Measured: Completed 8th month of life
Secondary outcomes (1)
hemangioma size
Size is measured with calipers and ultrasound
Measured: completed 8 th month of life
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2010 (estimated)
- Study startAug 2008
- Primary completionOct 2013
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HemangiomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hannover Medical School
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Carsten Engelmann, Hannover Medical School
- Investigators
- Carsten R Engelmann, MD PhD, Principal investigator, Hannover Medical SchoolBenno M Ure, Prof., Study director, Hannover Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01211080
- Sponsor's protocol ID
- AB 3
- Acronym
- PIHS
- Status last verified
- Nov 2014
- First submitted
- 28 Sep 2010
- Last updated
- 11 Nov 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 20644039
Study at a glance
From the registry record, last updated by the sponsor on 11 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Uncontrolled Study of the Off Label Use of Propranolol for Infancy Hemangiomas to Identify Side Effects
- ClinicalTrials.gov ID
- NCT01211080
- Acronym / sponsor ID
- PIHS / AB 3
- Conditions
- Hemangioma
- Keywords
- infancy hemangioma, propranolol, study design, side effects, safety
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Hannover Medical SchoolUniversity, hospital or other
- Study start
- Aug 2008
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 29 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Threatening hemangioma | – | Drug: PropranololThe 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) |
Who may qualify
- Ages
- 1 month to 8 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Tertiary and Secondary Pediatric Surgery Referral unit Secondary Care Pediatrics Unit
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- "Uncomplicated" Hemangiomas (trunk, extremities), infants with heart disease, known arrhythmias, bronchoobstructive disease, known hypoglycaemia events.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PropranololPropranolol 2mg/kg/day divided to three oral doses with or without concomitant physical therapy (cryotherapy, laser) | Drug | Threatening hemangioma |
Primary outcome
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
1 secondary outcome
hemangioma size
Time frame: completed 8 th month of life
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Nov 2014.
- Background: PubMed 20644039Holland 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.
- university web site/englishLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carsten R Engelmann, MD PhD principal investigator
Hannover Medical School
Benno M Ure, Prof. study director
Hannover Medical School
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hemangioma, run by Hannover Medical School at 3 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cosmesis of the lesion and surrounding skin (time frame: Completed 8 months of life). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01211080, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Nov 2014.