Hemangioma of Infancy
Conditions
Keywords
hemangioma
Brief summary
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.
Detailed description
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.
Interventions
DRUGpropranolol
propranolol 0.5 mg/kg orally, 4 per day - 4-6 months
DRUGPrednisolone
1.0 mg/kg orally, 2 per day 4-6 months
Sponsors
Nancy Bauman
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Weeks to 6 Months
Healthy volunteers
No
Inclusion criteria
* infants with symptomatic hemangiomas
Exclusion criteria
* asthma * diabetes * hypertension * hypotension * hypoglycemia * liver failure * previous treatment for hemangiomas
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Decrease in Size of Hemangioma (Length x Width) in Square mm | 4-5 months after initiating therapy | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Serious Adverse Events (SAEs) | enrollment until study close out or withdrawal up to 9 months | 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. |
| Growth and Development Adverse Events | enrollment to study withdrawal or close out up to 9 months | Number of Growth and Development AEs in each study arm |
| Pulmonary/Respiratory Adverse Events | enrollment through study close out or withdrawal, up to 9 months | Number of pulmonary/respiratory adverse events (CTCAE 22) in each study arm |
| Allergy/Immunology Adverse Events | enrollment through study closeout or study withdrawal up to 9 months | Number of allergy/immunology AE per study arm |
| Dermatologic Adverse Events | enrollment to study close out or withdrawal up to 9 months | Number of Dermatologic Adverse Events in each study arm. |
| Tolerability of Medication | enrollment until study close out or withdrawal up to 9 months | All adverse events relating to medication tolerability including: adrenal crisis, growth/development, constitutional (dehydration), allergy/immunology, dermatologic, endocrine, GI, infection, metabolism/labs, pulmonary, vascular. |
| Gastrointestinal Adverse Events | enrollment to study withdrawal or study close out up to 9 months | Number of Gastrointestinal AEs in each arm |
| Infectious Adverse Events | enrollment to study withdrawal or close out up to 9 months | Number of infectious AEs in each study arm (i.e. conjunctivitis, thrush, fever) |
| Metabolic or Laboratory AEs | enrollment to study withdrawal or close out up to 9 months | Number of Metabolic or Laboratory AEs in each study arm. |
| Vascular Adverse Events | enrollment to study withdrawal or close out up to 9 months | Number of Vascular AEs in each study arm. |
| Constitutional Adverse Events | enrollment to study close out or withdrawal up to 9 months | Number of constitutional AEs in each study arm. |
| Endocrinologic Adverse Events | enrollment to close out or study withdrawal up to 9 months | Number of Endocrinologic AEs (of which adrenal crisis does not overlap). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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) | 11 |
| 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 4-6 months (2.0 mg/kg/day) | 8 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 5 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 2 | 0 |
Baseline characteristics
| Characteristic | Prednisolone | Total | Propranolol |
|---|---|---|---|
| Adjusted total surface area (length x width x proportion of skin involved | 2.5 mm squared | 4.0 mm squared | 5.0 mm squared |
| Age, Continuous | 2.5 months | 3.4 months | 4.0 months |
| Depth deep | 2 participants | 4 participants | 2 participants |
| Depth mixed | 4 participants | 10 participants | 6 participants |
| Depth superficial | 2 participants | 5 participants | 3 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 10 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 9 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Morphology Intermediate | 0 participants | 2 participants | 2 participants |
| Morphology Local | 8 participants | 14 participants | 6 participants |
| Morphology Segmental | 0 participants | 3 participants | 3 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 15 Participants | 9 Participants |
| Region of Enrollment United States | 8 participants | 19 participants | 11 participants |
| Sex: Female, Male Female | 6 Participants | 14 Participants | 8 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 3 Participants |
| Total surface area (length x width) | 3.1 mm squared | 4.2 mm squared | 5.0 mm squared |
| Ulceration | 1 participants | 3 participants | 2 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 11 | 8 / 8 |
| serious Total, serious adverse events | 1 / 11 | 5 / 8 |
Outcome results
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.
Time frame: 4-5 months after initiating therapy
Population: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Propranolol | Decrease in Size of Hemangioma (Length x Width) in Square mm | 0.57 mm squared |
| Prednisolone | Decrease in Size of Hemangioma (Length x Width) in Square mm | 0.63 mm squared |
Comparison: intention to treat analysisp-value: 0.77t-test, 2 sided
Secondary
Allergy/Immunology Adverse Events
Number of allergy/immunology AE per study arm
Time frame: enrollment through study closeout or study withdrawal up to 9 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Propranolol | Allergy/Immunology Adverse Events | 1 Adverse Events |
| Prednisolone | Allergy/Immunology Adverse Events | 1 Adverse Events |
Secondary
Constitutional Adverse Events
Number of constitutional AEs in each study arm.
Time frame: enrollment to study close out or withdrawal up to 9 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Propranolol | Constitutional Adverse Events | 2 Adverse Events |
| Prednisolone | Constitutional Adverse Events | 3 Adverse Events |
Secondary
Dermatologic Adverse Events
Number of Dermatologic Adverse Events in each study arm.
Time frame: enrollment to study close out or withdrawal up to 9 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Propranolol | Dermatologic Adverse Events | 2 Adverse Events |
| Prednisolone | Dermatologic Adverse Events | 1 Adverse Events |
Secondary
Endocrinologic Adverse Events
Number of Endocrinologic AEs (of which adrenal crisis does not overlap).
Time frame: enrollment to close out or study withdrawal up to 9 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Propranolol | Endocrinologic Adverse Events | 0 Adverse Events |
| Prednisolone | Endocrinologic Adverse Events | 7 Adverse Events |
Secondary
Gastrointestinal Adverse Events
Number of Gastrointestinal AEs in each arm
Time frame: enrollment to study withdrawal or study close out up to 9 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Propranolol | Gastrointestinal Adverse Events | 6 Adverse Events |
| Prednisolone | Gastrointestinal Adverse Events | 6 Adverse Events |
Secondary
Growth and Development Adverse Events
Number of Growth and Development AEs in each study arm
Time frame: enrollment to study withdrawal or close out up to 9 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Propranolol | Growth and Development Adverse Events | 0 Adverse Events |
| Prednisolone | Growth and Development Adverse Events | 1 Adverse Events |
Secondary
Infectious Adverse Events
Number of infectious AEs in each study arm (i.e. conjunctivitis, thrush, fever)
Time frame: enrollment to study withdrawal or close out up to 9 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Propranolol | Infectious Adverse Events | 5 Adverse Events |
| Prednisolone | Infectious Adverse Events | 3 Adverse Events |
Secondary
Metabolic or Laboratory AEs
Number of Metabolic or Laboratory AEs in each study arm.
Time frame: enrollment to study withdrawal or close out up to 9 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Propranolol | Metabolic or Laboratory AEs | 1 Adverse Events |
| Prednisolone | Metabolic or Laboratory AEs | 0 Adverse Events |
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.
Time frame: enrollment until study close out or withdrawal up to 9 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Propranolol | Number of Serious Adverse Events (SAEs) | 1 Serious Adverse Events |
| Prednisolone | Number of Serious Adverse Events (SAEs) | 11 Serious Adverse Events |
Secondary
Pulmonary/Respiratory Adverse Events
Number of pulmonary/respiratory adverse events (CTCAE 22) in each study arm
Time frame: enrollment through study close out or withdrawal, up to 9 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Propranolol | Pulmonary/Respiratory Adverse Events | 14 Adverse Events |
| Prednisolone | Pulmonary/Respiratory Adverse Events | 4 Adverse Events |
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.
Time frame: enrollment until study close out or withdrawal up to 9 months
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Propranolol | Tolerability of Medication | Adverse Events | 34 Events |
| Propranolol | Tolerability of Medication | Serious Adverse Events | 1 Events |
| Prednisolone | Tolerability of Medication | Adverse Events | 30 Events |
| Prednisolone | Tolerability of Medication | Serious Adverse Events | 11 Events |
Secondary
Vascular Adverse Events
Number of Vascular AEs in each study arm.
Time frame: enrollment to study withdrawal or close out up to 9 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Propranolol | Vascular Adverse Events | 3 Adverse Events |
| Prednisolone | Vascular Adverse Events | 4 Adverse Events |