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| ID | Type | Description | Link |
|---|---|---|---|
| NIH grant number 10179326 |
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Serious adverse events with prednisolone, primarily temporary growth retardation, <5th percentile.
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Hemangiomas are relatively common lesions in infants. Most go away spontaneously after one year of life and do not need treatment. Others require treatment because they cause significant symptoms such as pain, or difficulty with breathing, eating or ambulating. Steroids have classically been used to treat hemangiomas and help to shrink them in 1/3 - 2/3 of patients. Unfortunately, steroids have many side effects in babies so physicians have sought other ways to treat them. Recently, the use of propranolol, a heart medication, was serendipitously found to reduce the size of hemangiomas. It appears to have many fewer side effects than steroids but it is not yet known if it works as well as steroids. This study seeks to compare the effect and the side effects of propranolol versus steroids for treating hemangiomas that cause symptoms in infants.
Infants with symptomatic hemangiomas will be enrolled. Magnetic resonance imaging will be completed before starting medication if the extent of the hemangioma is not evident on clinical examination alone. Infants will be randomized to receive either propranolol or steroids for 4-6 months. Hemangioma response will be measured and compared monthly as will tolerability of the medications. Additionally, urine specimens will be collected at each visit to determine if markers are present that can predict response to therapy.
Additionally, any hemangiomas that are excised will be examined for genetic markers to aid in predicting response to therapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| propranolol for treatment of hemangiomas | Experimental | Assessing efficacy and tolerability of propranolol in management of symptomatic hemangiomas |
|
| Prednisolone | Active Comparator | Assessing efficacy and tolerability of prednisolone in management of symptomatic hemangiomas and comparing to propranolol. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| propranolol | Drug | propranolol 0.5 mg/kg orally, 4 per day - 4-6 months |
|
| Measure | Description | Time Frame |
|---|---|---|
| Decrease in Size of Hemangioma (Length x Width) in Square mm | A priori primary outcome was proportional change in the total surface area as measured by lesion's outer margin length x width at baseline minus the same measure at 4 months with surrogate data used at 5 months if 4 months not available. | 4-5 months after initiating therapy |
| Measure | Description | Time Frame |
|---|---|---|
| Tolerability of Medication | All adverse events relating to medication tolerability including: adrenal crisis, growth/development, constitutional (dehydration), allergy/immunology, dermatologic, endocrine, GI, infection, metabolism/labs, pulmonary, vascular. | enrollment until study close out or withdrawal up to 9 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nancy M Bauman, MD | Children's Research Institute, Children's National Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's National Medical Center | Washington D.C. | District of Columbia | 20111 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19631595 | Background | Perez RS, Mora PC, Rodriguez JD, Sanchez FR, de Torres Jde L. [Treatment of infantile hemangioma with propranolol]. An Pediatr (Barc). 2010 Feb;72(2):152-4. doi: 10.1016/j.anpedi.2009.05.019. Epub 2009 Jul 23. No abstract available. Spanish. | |
| 19481268 | Background | Denoyelle F, Leboulanger N, Enjolras O, Harris R, Roger G, Garabedian EN. Role of Propranolol in the therapeutic strategy of infantile laryngotracheal hemangioma. Int J Pediatr Otorhinolaryngol. 2009 Aug;73(8):1168-72. doi: 10.1016/j.ijporl.2009.04.025. Epub 2009 May 29. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Propranolol | Assessing efficacy and tolerability of propranolol in management of symptomatic hemangiomas propranolol: propranolol 0.67 mg/kg p.o. TID 4-6 months |
| FG001 | Prednisolone | Assessing efficacy and tolerability of prednisolone in management of symptomatic hemangiomas and comparing to propranolol. Prednisolone: 1.0 mg/kg p.o. BID 4-6 months |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Infants 2 weeks - 6 months of age with symptomatic, proliferating, infantile hemangiomas
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| ID | Title | Description |
|---|---|---|
| BG000 | Propranolol | Assessing efficacy and tolerability of propranolol in management of symptomatic hemangiomas Propranolol 0.67 mg/kg p.o. TID x 4 - 6 months (2.0 mg/kg/day) |
| BG001 | Prednisolone |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Decrease in Size of Hemangioma (Length x Width) in Square mm | A priori primary outcome was proportional change in the total surface area as measured by lesion's outer margin length x width at baseline minus the same measure at 4 months with surrogate data used at 5 months if 4 months not available. | Data available at 4 or 5 months for only 9/11 propranolol participants and for 6/8 prednisolone participants due to missed appointments. Overall, 90% (138/154) study appointments were completed. | Posted | Mean | 95% Confidence Interval | mm squared | 4-5 months after initiating therapy |
|
Adverse events collected in first 9 months participants treated with medication.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Propranolol | Assessing efficacy and tolerability of propranolol in management of symptomatic hemangiomas propranolol: propranolol 0.5 mg/kg p.o. QID 6 months or less |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Adrenal Crisis | Endocrine disorders | CTCAE | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dermatologic | Skin and subcutaneous tissue disorders | CTCAE | Systematic Assessment |
Not every enrolled participant had an adverse event and some had more than one. The prednioslone participants who had adverse events warranting early withdrawal had severe failure to thrive (<5th percentile), a serious adverse event.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Nancy M. Bauman MD, Principle Investigator | Childrens Research Institute | 2024764270 | nbauman@cnmc.org |
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| ID | Term |
|---|---|
| D006391 | Hemangioma |
| ID | Term |
|---|---|
| D009383 | Neoplasms, Vascular Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D011433 | Propranolol |
| D011239 | Prednisolone |
| C009022 | prednisolone phosphate |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
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| Prednisolone | Drug | 1.0 mg/kg orally, 2 per day 4-6 months |
|
|
| Number of Serious Adverse Events (SAEs) |
Number of serious adverse events experienced by the participants in each treatment arm within the categories adrenal crisis, growth/development, constitutional. Serious adverse events are defined as events that result in death, require either inpatient hospitalization or the prolongation of hospitalization, are life-threatening, result in a persistent or significant disability/incapacity, or result in a congenital anomaly/birth defect. Other important medical events, based upon appropriate medical judgment, may also be considered Serious Adverse Events if a trial participant's health is at risk and intervention is required to prevent an outcome mentioned. |
| enrollment until study close out or withdrawal up to 9 months |
| Growth and Development Adverse Events | Number of Growth and Development AEs in each study arm | enrollment to study withdrawal or close out up to 9 months |
| Pulmonary/Respiratory Adverse Events | Number of pulmonary/respiratory adverse events (CTCAE 22) in each study arm | enrollment through study close out or withdrawal, up to 9 months |
| Allergy/Immunology Adverse Events | Number of allergy/immunology AE per study arm | enrollment through study closeout or study withdrawal up to 9 months |
| Dermatologic Adverse Events | Number of Dermatologic Adverse Events in each study arm. | enrollment to study close out or withdrawal up to 9 months |
| Endocrinologic Adverse Events | Number of Endocrinologic AEs (of which adrenal crisis does not overlap). | enrollment to close out or study withdrawal up to 9 months |
| Gastrointestinal Adverse Events | Number of Gastrointestinal AEs in each arm | enrollment to study withdrawal or study close out up to 9 months |
| Infectious Adverse Events | Number of infectious AEs in each study arm (i.e. conjunctivitis, thrush, fever) | enrollment to study withdrawal or close out up to 9 months |
| Metabolic or Laboratory AEs | Number of Metabolic or Laboratory AEs in each study arm. | enrollment to study withdrawal or close out up to 9 months |
| Vascular Adverse Events | Number of Vascular AEs in each study arm. | enrollment to study withdrawal or close out up to 9 months |
| Constitutional Adverse Events | Number of constitutional AEs in each study arm. | enrollment to study close out or withdrawal up to 9 months |
| 18550886 | Background | Leaute-Labreze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Taieb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008 Jun 12;358(24):2649-51. doi: 10.1056/NEJMc0708819. No abstract available. |
| 24526257 | Derived | Bauman NM, McCarter RJ, Guzzetta PC, Shin JJ, Oh AK, Preciado DA, He J, Greene EA, Puttgen KB. Propranolol vs prednisolone for symptomatic proliferating infantile hemangiomas: a randomized clinical trial. JAMA Otolaryngol Head Neck Surg. 2014 Apr;140(4):323-30. doi: 10.1001/jamaoto.2013.6723. |
| 24347141 | Derived | Patel NJ, Bauman NM. How should propranolol be initiated for infantile hemangiomas: inpatient versus outpatient? Laryngoscope. 2014 Jun;124(6):1279-81. doi: 10.1002/lary.24363. Epub 2013 Dec 17. No abstract available. |
| Physician Decision |
|
Assessing efficacy and tolerability of prednisolone in management of symptomatic hemangiomas and comparing to propranolol.
Prednisolone: 1.0 mg/kg p.o. BID x 4-6 months (2.0 mg/kg/day)
| BG002 | Total | Total of all reporting groups |
| months |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Total surface area (length x width) | Mean | Full Range | mm squared |
|
| Adjusted total surface area (length x width x proportion of skin involved | Mean | Full Range | mm squared |
|
| Ulceration | (not present in all participants) | Number | participants |
|
| Morphology | Local, Segmental, Intermediate | Number | participants |
|
| Depth | Number | participants |
|
| Prednisolone |
A priori analysis, TSA (length x width) at baseline versus at 4 months with surrogate data at 5 months Prednisolone: 1.0 mg/kg p.o. BID x 4-6 months (2.0 mg/kg/day) |
|
|
|
| Secondary | Tolerability of Medication | All adverse events relating to medication tolerability including: adrenal crisis, growth/development, constitutional (dehydration), allergy/immunology, dermatologic, endocrine, GI, infection, metabolism/labs, pulmonary, vascular. | All adverse events relating to medication tolerability including: adrenal crisis, growth/development, constitutional (dehydration), allergy/immunology, dermatologic, endocrine, GI, infection, metabolism/labs, pulmonary, vascular. In this table "Adverse Events" are those exclusive of the "Serious Adverse Events" which are noted separately. | Posted | Number | Events | enrollment until study close out or withdrawal up to 9 months |
|
|
|
| Secondary | Number of Serious Adverse Events (SAEs) | Number of serious adverse events experienced by the participants in each treatment arm within the categories adrenal crisis, growth/development, constitutional. Serious adverse events are defined as events that result in death, require either inpatient hospitalization or the prolongation of hospitalization, are life-threatening, result in a persistent or significant disability/incapacity, or result in a congenital anomaly/birth defect. Other important medical events, based upon appropriate medical judgment, may also be considered Serious Adverse Events if a trial participant's health is at risk and intervention is required to prevent an outcome mentioned. | Posted | Number | Serious Adverse Events | enrollment until study close out or withdrawal up to 9 months |
|
|
|
| Secondary | Growth and Development Adverse Events | Number of Growth and Development AEs in each study arm | Posted | Number | Adverse Events | enrollment to study withdrawal or close out up to 9 months |
|
|
|
| Secondary | Pulmonary/Respiratory Adverse Events | Number of pulmonary/respiratory adverse events (CTCAE 22) in each study arm | Posted | Number | Adverse Events | enrollment through study close out or withdrawal, up to 9 months |
|
|
|
| Secondary | Allergy/Immunology Adverse Events | Number of allergy/immunology AE per study arm | Posted | Number | Adverse Events | enrollment through study closeout or study withdrawal up to 9 months |
|
|
|
| Secondary | Dermatologic Adverse Events | Number of Dermatologic Adverse Events in each study arm. | Posted | Number | Adverse Events | enrollment to study close out or withdrawal up to 9 months |
|
|
|
| Secondary | Endocrinologic Adverse Events | Number of Endocrinologic AEs (of which adrenal crisis does not overlap). | Posted | Number | Adverse Events | enrollment to close out or study withdrawal up to 9 months |
|
|
|
| Secondary | Gastrointestinal Adverse Events | Number of Gastrointestinal AEs in each arm | Posted | Number | Adverse Events | enrollment to study withdrawal or study close out up to 9 months |
|
|
|
| Secondary | Infectious Adverse Events | Number of infectious AEs in each study arm (i.e. conjunctivitis, thrush, fever) | Posted | Number | Adverse Events | enrollment to study withdrawal or close out up to 9 months |
|
|
|
| Secondary | Metabolic or Laboratory AEs | Number of Metabolic or Laboratory AEs in each study arm. | Posted | Number | Adverse Events | enrollment to study withdrawal or close out up to 9 months |
|
|
|
| Secondary | Vascular Adverse Events | Number of Vascular AEs in each study arm. | Posted | Number | Adverse Events | enrollment to study withdrawal or close out up to 9 months |
|
|
|
| Secondary | Constitutional Adverse Events | Number of constitutional AEs in each study arm. | Posted | Number | Adverse Events | enrollment to study close out or withdrawal up to 9 months |
|
|
|
| 1 |
| 11 |
| 11 |
| 11 |
| EG001 | Prednisolone | Assessing efficacy and tolerability of prednisolone in management of symptomatic hemangiomas and comparing to propranolol. Prednisolone: 1.0 mg/kg p.o. BID x 6 months or less | 5 | 8 | 8 | 8 |
| Failure to thrive | Metabolism and nutrition disorders | CTCAE | Systematic Assessment |
|
| Dehydration | General disorders | CTCAE | Systematic Assessment |
|
| Gastrointerstinal | Gastrointestinal disorders | CTCAE | Systematic Assessment |
|
| Infection | Infections and infestations | CTCAE | Systematic Assessment |
|
| Metabolic/Lab | Metabolism and nutrition disorders | CTCAE | Systematic Assessment |
|
| Pulmonary/respiratory | Respiratory, thoracic and mediastinal disorders | CTCAE | Systematic Assessment |
|
| Vascular | Vascular disorders | CTCAE | Systematic Assessment |
|
| Endo | Endocrine disorders | CTCAE | Systematic Assessment |
|
| Allergy | General disorders | CTCAE | Systematic Assessment |
|
| Constitutional | General disorders | CTCAE | Systematic Assessment |
|
| Growth suppression | Musculoskeletal and connective tissue disorders | CTCAE | Systematic Assessment |
|
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| D009930 |
| Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |