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Propranolol Versus Prednisolone for Treatment of Symptomatic Hemangiomas

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ClinicalTrials.gov Identifier: NCT00967226
Recruitment Status : Terminated (Serious adverse events with prednisolone, primarily temporary growth retardation, <5th percentile.)
First Posted : August 27, 2009
Results First Posted : February 24, 2016
Last Update Posted : February 24, 2016
Sponsor:
Information provided by (Responsible Party):
Nancy Bauman, Children's Research Institute

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Treatment
Condition Hemangioma of Infancy
Interventions Drug: propranolol
Drug: Prednisolone
Enrollment 19

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Propranolol Prednisolone
Hide Arm/Group Description

Assessing efficacy and tolerability of propranolol in management of symptomatic hemangiomas

propranolol: propranolol 0.67 mg/kg p.o. TID 4-6 months

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

Period Title: Overall Study
Started 11 8
Completed 9 2
Not Completed 2 6
Reason Not Completed
Adverse Event             0             5
Protocol Violation             2             0
Physician Decision             0             1
Arm/Group Title Propranolol Prednisolone Total
Hide Arm/Group Description

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)

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 of all reporting groups
Overall Number of Baseline Participants 11 8 19
Hide Baseline Analysis Population Description
Infants 2 weeks - 6 months of age with symptomatic, proliferating, infantile hemangiomas
Age, Continuous  
Mean (Full Range)
Unit of measure:  Months
Number Analyzed 11 participants 8 participants 19 participants
4.0
(2.8 to 5.2)
2.5
(1.7 to 3.4)
3.4
(1.7 to 5.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 8 participants 19 participants
Female
8
  72.7%
6
  75.0%
14
  73.7%
Male
3
  27.3%
2
  25.0%
5
  26.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 8 participants 19 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   9.1%
0
   0.0%
1
   5.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   9.1%
2
  25.0%
3
  15.8%
White
9
  81.8%
6
  75.0%
15
  78.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 8 participants 19 participants
Hispanic or Latino
5
  45.5%
5
  62.5%
10
  52.6%
Not Hispanic or Latino
6
  54.5%
3
  37.5%
9
  47.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 11 participants 8 participants 19 participants
11 8 19
Total surface area (length x width)  
Mean (Full Range)
Unit of measure:  Mm squared
Number Analyzed 11 participants 8 participants 19 participants
5.0
(1.9 to 25.6)
3.1
(0.8 to 10.5)
4.2
(0.8 to 25.6)
Adjusted total surface area (length x width x proportion of skin involved  
Mean (Full Range)
Unit of measure:  Mm squared
Number Analyzed 11 participants 8 participants 19 participants
5.0
(1.5 to 24.3)
2.5
(0.2 to 9.4)
4.0
(0.2 to 24.3)
Ulceration   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 11 participants 8 participants 19 participants
2 1 3
[1]
Measure Description: (not present in all participants)
Morphology   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 11 participants 8 participants 19 participants
Local 6 8 14
Segmental 3 0 3
Intermediate 2 0 2
[1]
Measure Description: Local, Segmental, Intermediate
Depth  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 11 participants 8 participants 19 participants
superficial 3 2 5
deep 2 2 4
mixed 6 4 10
1.Primary Outcome
Title Decrease in Size of Hemangioma (Length x Width) in Square mm
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Propranolol Prednisolone
Hide Arm/Group Description:
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)

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)

Overall Number of Participants Analyzed 9 6
Mean (95% Confidence Interval)
Unit of Measure: mm squared
0.57
(0.34 to 0.80)
0.63
(0.14 to 1.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Propranolol, Prednisolone
Comments intention to treat analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.77
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.06
Parameter Dispersion
Type: Standard Deviation
Value: 0.05
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Tolerability of Medication
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Overall Number of Adverse Events in Propranolol Overall Number of Adverse Events in Prednisolone
Hide Arm/Group Description:
All (total) study adverse events displayed as "Adverse events" including mild, moderate, and severe; as well as "Serious Adverse Events"
All (total) study adverse events displayed as "Adverse events" including mild, moderate, and severe; as well as "Serious Adverse Events"
Overall Number of Participants Analyzed 11 8
Measure Type: Number
Unit of Measure: Events
Adverse Events 34 30
Serious Adverse Events 1 11
3.Secondary Outcome
Title Number of Serious Adverse Events (SAEs)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Number of Serious Adverse Events in Propranolol Number of Serious Adverse Events in Prednisolone
Hide Arm/Group Description:
Serious adverse events in propranolol treated participants.
Serious adverse events in prednisolone treated participants
Overall Number of Participants Analyzed 11 8
Measure Type: Number
Unit of Measure: Serious Adverse Events
1 11
4.Secondary Outcome
Title Growth and Development Adverse Events
Hide Description Number of Growth and Development AEs in each study arm
Time Frame enrollment to study withdrawal or close out up to 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Growth/Developoment AEs Propranolol Growth/Development AEs Prednisolone
Hide Arm/Group Description:
Number of participants experiencing Growth/Development AEs
Number of participants experiencing Growth/Development AEs
Overall Number of Participants Analyzed 11 8
Measure Type: Number
Unit of Measure: Adverse Events
0 1
5.Secondary Outcome
Title Pulmonary/Respiratory Adverse Events
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pulmonary/Respiratory AEs Propranolol Pulmonary/Respiratory AEs Prednisolone
Hide Arm/Group Description:
Number of participants experiencing pulmonary/respiratory AEs
Number of participants experiencing pulmonary/respiratory AEs
Overall Number of Participants Analyzed 11 8
Measure Type: Number
Unit of Measure: Adverse Events
14 4
6.Secondary Outcome
Title Allergy/Immunology Adverse Events
Hide Description Number of allergy/immunology AE per study arm
Time Frame enrollment through study closeout or study withdrawal up to 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Allergy/Immunology Events Propranolol Allergy/Immunology Events Prednisolone
Hide Arm/Group Description:
Adverse events in allergy/immunology in propranolol treated participants
Adverse events in allergy/immunology in prednisolone treated participants
Overall Number of Participants Analyzed 11 8
Measure Type: Number
Unit of Measure: Adverse Events
1 1
7.Secondary Outcome
Title Dermatologic Adverse Events
Hide Description Number of Dermatologic Adverse Events in each study arm.
Time Frame enrollment to study close out or withdrawal up to 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dermatologic AEs Propranolol Dermatologic AEs Prednisolone
Hide Arm/Group Description:
Number of participants experiencing Dermatologic AEs
Number of participants experiencing Dermatologic AEs
Overall Number of Participants Analyzed 11 8
Measure Type: Number
Unit of Measure: Adverse Events
2 1
8.Secondary Outcome
Title Endocrinologic Adverse Events
Hide Description Number of Endocrinologic AEs (of which adrenal crisis does not overlap).
Time Frame enrollment to close out or study withdrawal up to 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Endocrine AEs Propranolol Endocrinologic AEs Prednisolone
Hide Arm/Group Description:
Number of participants experiencing Endocrinologic AEs.
Number of participants experiencing Endocrinologic AEs.
Overall Number of Participants Analyzed 11 8
Measure Type: Number
Unit of Measure: Adverse Events
0 7
9.Secondary Outcome
Title Gastrointestinal Adverse Events
Hide Description Number of Gastrointestinal AEs in each arm
Time Frame enrollment to study withdrawal or study close out up to 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Gastrointestinal AEs Propranolol Gastrointestinal AEs Prednisolone
Hide Arm/Group Description:
Number of Participants experiencing Gastrointestinal AEs
Number of Participants experiencing Gastrointestinal AEs
Overall Number of Participants Analyzed 11 8
Measure Type: Number
Unit of Measure: Adverse Events
6 6
10.Secondary Outcome
Title Infectious Adverse Events
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Infectious AEs Propranolol Infectious AEs Prednisolone
Hide Arm/Group Description:
Number of participants experiencing Infectious AEs
Number of participants experiencing Infectious AEs
Overall Number of Participants Analyzed 11 8
Measure Type: Number
Unit of Measure: Adverse Events
5 3
11.Secondary Outcome
Title Metabolic or Laboratory AEs
Hide Description Number of Metabolic or Laboratory AEs in each study arm.
Time Frame enrollment to study withdrawal or close out up to 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Metabolic/Laboratory AEs Propranolol Metabolic/Laboratory AEs Prednisolone
Hide Arm/Group Description:
Number of participants experiencing Metabolic or Laboratory AEs.
Number of participants experiencing Metabolic or Laboratory AEs in each study arm.
Overall Number of Participants Analyzed 11 8
Measure Type: Number
Unit of Measure: Adverse Events
1 0
12.Secondary Outcome
Title Vascular Adverse Events
Hide Description Number of Vascular AEs in each study arm.
Time Frame enrollment to study withdrawal or close out up to 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vascular AEs Propranolol Vascular AEs Prednisolone
Hide Arm/Group Description:
Number of participants experiencing Vascular AEs
Number of participants experiencing Vascular AEs
Overall Number of Participants Analyzed 11 8
Measure Type: Number
Unit of Measure: Adverse Events
3 4
13.Secondary Outcome
Title Constitutional Adverse Events
Hide Description Number of constitutional AEs in each study arm.
Time Frame enrollment to study close out or withdrawal up to 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Constitutional AEs Propranolol Constitutional AEs Prednisolone
Hide Arm/Group Description:
Number of Participants experiencing Constitutional AEs
Number of Participants experiencing Constitutional AEs
Overall Number of Participants Analyzed 11 8
Measure Type: Number
Unit of Measure: Adverse Events
2 3
Time Frame Adverse events collected in first 9 months participants treated with medication.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Propranolol Prednisolone
Hide Arm/Group Description

Assessing efficacy and tolerability of propranolol in management of symptomatic hemangiomas

propranolol: propranolol 0.5 mg/kg p.o. QID 6 months or less

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

All-Cause Mortality
Propranolol Prednisolone
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Propranolol Prednisolone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/11 (9.09%)      5/8 (62.50%)    
Endocrine disorders     
Adrenal Crisis  1  0/11 (0.00%)  0 1/8 (12.50%)  1
General disorders     
Dehydration  1  1/11 (9.09%)  1 1/8 (12.50%)  1
Metabolism and nutrition disorders     
Failure to thrive  1  0/11 (0.00%)  0 5/8 (62.50%)  9
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Propranolol Prednisolone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/11 (100.00%)      8/8 (100.00%)    
Endocrine disorders     
Endo  1  0/11 (0.00%)  0 6/8 (75.00%)  7
Gastrointestinal disorders     
Gastrointerstinal  1  5/11 (45.45%)  6 5/8 (62.50%)  6
General disorders     
Allergy  1  1/11 (9.09%)  1 1/8 (12.50%)  1
Constitutional  1  2/11 (18.18%)  2 3/8 (37.50%)  3
Infections and infestations     
Infection  1  2/11 (18.18%)  5 2/8 (25.00%)  3
Metabolism and nutrition disorders     
Metabolic/Lab  1  1/11 (9.09%)  1 0/8 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Growth suppression  1  0/11 (0.00%)  0 1/8 (12.50%)  1
Respiratory, thoracic and mediastinal disorders     
Pulmonary/respiratory  1  8/11 (72.73%)  14 3/8 (37.50%)  4
Skin and subcutaneous tissue disorders     
Dermatologic  1  2/11 (18.18%)  2 1/8 (12.50%)  1
Vascular disorders     
Vascular  1  3/11 (27.27%)  3 1/8 (12.50%)  4
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE
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.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Nancy M. Bauman MD, Principle Investigator
Organization: Childrens Research Institute
Phone: 2024764270
Responsible Party: Nancy Bauman, Children's Research Institute
ClinicalTrials.gov Identifier: NCT00967226     History of Changes
Other Study ID Numbers: IRB 4502
NIH grant number 10179326
First Submitted: August 26, 2009
First Posted: August 27, 2009
Results First Submitted: March 14, 2014
Results First Posted: February 24, 2016
Last Update Posted: February 24, 2016