Trial Outcomes & Findings for Propranolol Versus Prednisolone for Treatment of Symptomatic Hemangiomas (NCT NCT00967226)
NCT ID: NCT00967226
Last Updated: 2016-02-24
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
19 participants
Primary outcome timeframe
4-5 months after initiating therapy
Results posted on
2016-02-24
Participant Flow
Participant milestones
| Measure |
Propranolol
Assessing efficacy and tolerability of propranolol in management of symptomatic hemangiomas
propranolol: propranolol 0.67 mg/kg p.o. TID 4-6 months
|
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
|
|---|---|---|
|
Overall Study
STARTED
|
11
|
8
|
|
Overall Study
COMPLETED
|
9
|
2
|
|
Overall Study
NOT COMPLETED
|
2
|
6
|
Reasons for withdrawal
| Measure |
Propranolol
Assessing efficacy and tolerability of propranolol in management of symptomatic hemangiomas
propranolol: propranolol 0.67 mg/kg p.o. TID 4-6 months
|
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
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
5
|
|
Overall Study
Protocol Violation
|
2
|
0
|
|
Overall Study
Physician Decision
|
0
|
1
|
Baseline Characteristics
Propranolol Versus Prednisolone for Treatment of Symptomatic Hemangiomas
Baseline characteristics by cohort
| Measure |
Propranolol
n=11 Participants
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)
|
Prednisolone
n=8 Participants
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)
|
Total
n=19 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
4.0 months
n=5 Participants
|
2.5 months
n=7 Participants
|
3.4 months
n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
11 participants
n=5 Participants
|
8 participants
n=7 Participants
|
19 participants
n=5 Participants
|
|
Total surface area (length x width)
|
5.0 mm squared
n=5 Participants
|
3.1 mm squared
n=7 Participants
|
4.2 mm squared
n=5 Participants
|
|
Adjusted total surface area (length x width x proportion of skin involved
|
5.0 mm squared
n=5 Participants
|
2.5 mm squared
n=7 Participants
|
4.0 mm squared
n=5 Participants
|
|
Ulceration
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Morphology
Local
|
6 participants
n=5 Participants
|
8 participants
n=7 Participants
|
14 participants
n=5 Participants
|
|
Morphology
Segmental
|
3 participants
n=5 Participants
|
0 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Morphology
Intermediate
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Depth
superficial
|
3 participants
n=5 Participants
|
2 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Depth
deep
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Depth
mixed
|
6 participants
n=5 Participants
|
4 participants
n=7 Participants
|
10 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 4-5 months after initiating therapyPopulation: 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.
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.
Outcome measures
| Measure |
Propranolol
n=9 Participants
A priori analysis, TSA (length x width) at baseline versus at 4 months with surrogate data at 5 months Propranolol 0.67 mg/kg p.o. TID x 4 - 6 months (2.0 mg/kg/day)
|
Prednisolone
n=6 Participants
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)
|
|---|---|---|
|
Decrease in Size of Hemangioma (Length x Width) in Square mm
|
0.57 mm squared
Interval 0.34 to 0.8
|
0.63 mm squared
Interval 0.14 to 1.11
|
SECONDARY outcome
Timeframe: enrollment until study close out or withdrawal up to 9 monthsPopulation: 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.
All adverse events relating to medication tolerability including: adrenal crisis, growth/development, constitutional (dehydration), allergy/immunology, dermatologic, endocrine, GI, infection, metabolism/labs, pulmonary, vascular.
Outcome measures
| Measure |
Propranolol
n=11 Participants
A priori analysis, TSA (length x width) at baseline versus at 4 months with surrogate data at 5 months Propranolol 0.67 mg/kg p.o. TID x 4 - 6 months (2.0 mg/kg/day)
|
Prednisolone
n=8 Participants
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)
|
|---|---|---|
|
Tolerability of Medication
Adverse Events
|
34 Events
|
30 Events
|
|
Tolerability of Medication
Serious Adverse Events
|
1 Events
|
11 Events
|
SECONDARY outcome
Timeframe: enrollment until study close out or withdrawal up to 9 monthsNumber 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.
Outcome measures
| Measure |
Propranolol
n=11 Participants
A priori analysis, TSA (length x width) at baseline versus at 4 months with surrogate data at 5 months Propranolol 0.67 mg/kg p.o. TID x 4 - 6 months (2.0 mg/kg/day)
|
Prednisolone
n=8 Participants
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)
|
|---|---|---|
|
Number of Serious Adverse Events (SAEs)
|
1 Serious Adverse Events
|
11 Serious Adverse Events
|
SECONDARY outcome
Timeframe: enrollment to study withdrawal or close out up to 9 monthsNumber of Growth and Development AEs in each study arm
Outcome measures
| Measure |
Propranolol
n=11 Participants
A priori analysis, TSA (length x width) at baseline versus at 4 months with surrogate data at 5 months Propranolol 0.67 mg/kg p.o. TID x 4 - 6 months (2.0 mg/kg/day)
|
Prednisolone
n=8 Participants
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)
|
|---|---|---|
|
Growth and Development Adverse Events
|
0 Adverse Events
|
1 Adverse Events
|
SECONDARY outcome
Timeframe: enrollment through study close out or withdrawal, up to 9 monthsNumber of pulmonary/respiratory adverse events (CTCAE 22) in each study arm
Outcome measures
| Measure |
Propranolol
n=11 Participants
A priori analysis, TSA (length x width) at baseline versus at 4 months with surrogate data at 5 months Propranolol 0.67 mg/kg p.o. TID x 4 - 6 months (2.0 mg/kg/day)
|
Prednisolone
n=8 Participants
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)
|
|---|---|---|
|
Pulmonary/Respiratory Adverse Events
|
14 Adverse Events
|
4 Adverse Events
|
SECONDARY outcome
Timeframe: enrollment through study closeout or study withdrawal up to 9 monthsNumber of allergy/immunology AE per study arm
Outcome measures
| Measure |
Propranolol
n=11 Participants
A priori analysis, TSA (length x width) at baseline versus at 4 months with surrogate data at 5 months Propranolol 0.67 mg/kg p.o. TID x 4 - 6 months (2.0 mg/kg/day)
|
Prednisolone
n=8 Participants
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)
|
|---|---|---|
|
Allergy/Immunology Adverse Events
|
1 Adverse Events
|
1 Adverse Events
|
SECONDARY outcome
Timeframe: enrollment to study close out or withdrawal up to 9 monthsNumber of Dermatologic Adverse Events in each study arm.
Outcome measures
| Measure |
Propranolol
n=11 Participants
A priori analysis, TSA (length x width) at baseline versus at 4 months with surrogate data at 5 months Propranolol 0.67 mg/kg p.o. TID x 4 - 6 months (2.0 mg/kg/day)
|
Prednisolone
n=8 Participants
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)
|
|---|---|---|
|
Dermatologic Adverse Events
|
2 Adverse Events
|
1 Adverse Events
|
SECONDARY outcome
Timeframe: enrollment to close out or study withdrawal up to 9 monthsNumber of Endocrinologic AEs (of which adrenal crisis does not overlap).
Outcome measures
| Measure |
Propranolol
n=11 Participants
A priori analysis, TSA (length x width) at baseline versus at 4 months with surrogate data at 5 months Propranolol 0.67 mg/kg p.o. TID x 4 - 6 months (2.0 mg/kg/day)
|
Prednisolone
n=8 Participants
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)
|
|---|---|---|
|
Endocrinologic Adverse Events
|
0 Adverse Events
|
7 Adverse Events
|
SECONDARY outcome
Timeframe: enrollment to study withdrawal or study close out up to 9 monthsNumber of Gastrointestinal AEs in each arm
Outcome measures
| Measure |
Propranolol
n=11 Participants
A priori analysis, TSA (length x width) at baseline versus at 4 months with surrogate data at 5 months Propranolol 0.67 mg/kg p.o. TID x 4 - 6 months (2.0 mg/kg/day)
|
Prednisolone
n=8 Participants
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)
|
|---|---|---|
|
Gastrointestinal Adverse Events
|
6 Adverse Events
|
6 Adverse Events
|
SECONDARY outcome
Timeframe: enrollment to study withdrawal or close out up to 9 monthsNumber of infectious AEs in each study arm (i.e. conjunctivitis, thrush, fever)
Outcome measures
| Measure |
Propranolol
n=11 Participants
A priori analysis, TSA (length x width) at baseline versus at 4 months with surrogate data at 5 months Propranolol 0.67 mg/kg p.o. TID x 4 - 6 months (2.0 mg/kg/day)
|
Prednisolone
n=8 Participants
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)
|
|---|---|---|
|
Infectious Adverse Events
|
5 Adverse Events
|
3 Adverse Events
|
SECONDARY outcome
Timeframe: enrollment to study withdrawal or close out up to 9 monthsNumber of Metabolic or Laboratory AEs in each study arm.
Outcome measures
| Measure |
Propranolol
n=11 Participants
A priori analysis, TSA (length x width) at baseline versus at 4 months with surrogate data at 5 months Propranolol 0.67 mg/kg p.o. TID x 4 - 6 months (2.0 mg/kg/day)
|
Prednisolone
n=8 Participants
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)
|
|---|---|---|
|
Metabolic or Laboratory AEs
|
1 Adverse Events
|
0 Adverse Events
|
SECONDARY outcome
Timeframe: enrollment to study withdrawal or close out up to 9 monthsNumber of Vascular AEs in each study arm.
Outcome measures
| Measure |
Propranolol
n=11 Participants
A priori analysis, TSA (length x width) at baseline versus at 4 months with surrogate data at 5 months Propranolol 0.67 mg/kg p.o. TID x 4 - 6 months (2.0 mg/kg/day)
|
Prednisolone
n=8 Participants
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)
|
|---|---|---|
|
Vascular Adverse Events
|
3 Adverse Events
|
4 Adverse Events
|
SECONDARY outcome
Timeframe: enrollment to study close out or withdrawal up to 9 monthsNumber of constitutional AEs in each study arm.
Outcome measures
| Measure |
Propranolol
n=11 Participants
A priori analysis, TSA (length x width) at baseline versus at 4 months with surrogate data at 5 months Propranolol 0.67 mg/kg p.o. TID x 4 - 6 months (2.0 mg/kg/day)
|
Prednisolone
n=8 Participants
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)
|
|---|---|---|
|
Constitutional Adverse Events
|
2 Adverse Events
|
3 Adverse Events
|
Adverse Events
Propranolol
Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths
Prednisolone
Serious events: 5 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Propranolol
n=11 participants at risk
Assessing efficacy and tolerability of propranolol in management of symptomatic hemangiomas
propranolol: propranolol 0.5 mg/kg p.o. QID 6 months or less
|
Prednisolone
n=8 participants at risk
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
|
|---|---|---|
|
Endocrine disorders
Adrenal Crisis
|
0.00%
0/11 • Adverse events collected in first 9 months participants treated with medication.
|
12.5%
1/8 • Number of events 1 • Adverse events collected in first 9 months participants treated with medication.
|
|
Metabolism and nutrition disorders
Failure to thrive
|
0.00%
0/11 • Adverse events collected in first 9 months participants treated with medication.
|
62.5%
5/8 • Number of events 9 • Adverse events collected in first 9 months participants treated with medication.
|
|
General disorders
Dehydration
|
9.1%
1/11 • Number of events 1 • Adverse events collected in first 9 months participants treated with medication.
|
12.5%
1/8 • Number of events 1 • Adverse events collected in first 9 months participants treated with medication.
|
Other adverse events
| Measure |
Propranolol
n=11 participants at risk
Assessing efficacy and tolerability of propranolol in management of symptomatic hemangiomas
propranolol: propranolol 0.5 mg/kg p.o. QID 6 months or less
|
Prednisolone
n=8 participants at risk
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
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Dermatologic
|
18.2%
2/11 • Number of events 2 • Adverse events collected in first 9 months participants treated with medication.
|
12.5%
1/8 • Number of events 1 • Adverse events collected in first 9 months participants treated with medication.
|
|
Gastrointestinal disorders
Gastrointerstinal
|
45.5%
5/11 • Number of events 6 • Adverse events collected in first 9 months participants treated with medication.
|
62.5%
5/8 • Number of events 6 • Adverse events collected in first 9 months participants treated with medication.
|
|
Infections and infestations
Infection
|
18.2%
2/11 • Number of events 5 • Adverse events collected in first 9 months participants treated with medication.
|
25.0%
2/8 • Number of events 3 • Adverse events collected in first 9 months participants treated with medication.
|
|
Metabolism and nutrition disorders
Metabolic/Lab
|
9.1%
1/11 • Number of events 1 • Adverse events collected in first 9 months participants treated with medication.
|
0.00%
0/8 • Adverse events collected in first 9 months participants treated with medication.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary/respiratory
|
72.7%
8/11 • Number of events 14 • Adverse events collected in first 9 months participants treated with medication.
|
37.5%
3/8 • Number of events 4 • Adverse events collected in first 9 months participants treated with medication.
|
|
Vascular disorders
Vascular
|
27.3%
3/11 • Number of events 3 • Adverse events collected in first 9 months participants treated with medication.
|
12.5%
1/8 • Number of events 4 • Adverse events collected in first 9 months participants treated with medication.
|
|
Endocrine disorders
Endo
|
0.00%
0/11 • Adverse events collected in first 9 months participants treated with medication.
|
75.0%
6/8 • Number of events 7 • Adverse events collected in first 9 months participants treated with medication.
|
|
General disorders
Allergy
|
9.1%
1/11 • Number of events 1 • Adverse events collected in first 9 months participants treated with medication.
|
12.5%
1/8 • Number of events 1 • Adverse events collected in first 9 months participants treated with medication.
|
|
General disorders
Constitutional
|
18.2%
2/11 • Number of events 2 • Adverse events collected in first 9 months participants treated with medication.
|
37.5%
3/8 • Number of events 3 • Adverse events collected in first 9 months participants treated with medication.
|
|
Musculoskeletal and connective tissue disorders
Growth suppression
|
0.00%
0/11 • Adverse events collected in first 9 months participants treated with medication.
|
12.5%
1/8 • Number of events 1 • Adverse events collected in first 9 months participants treated with medication.
|
Additional Information
Nancy M. Bauman MD, Principle Investigator
Childrens Research Institute
Phone: 2024764270
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place