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Study to Demonstrate the Efficacy and Safety of Propranolol Oral Solution in Infants With Proliferating Infantile Hemangiomas Requiring Systemic Therapy

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ClinicalTrials.gov Identifier: NCT01056341
Recruitment Status : Completed
First Posted : January 26, 2010
Results First Posted : June 24, 2014
Last Update Posted : December 10, 2015
Sponsor:
Information provided by (Responsible Party):
Pierre Fabre Dermatology

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Infantile Hemangioma
Interventions Drug: Propranolol
Drug: Placebo
Enrollment 512
Recruitment Details  
Pre-assignment Details

512 patients were included in the study (informed Consent Form signed). Among these 510 patients, 460 were randomized and 52 were screen failure

  • At least one inclusion criterion not met in 26 cases
  • Parent's decision in 12 cases
  • Other reasons in 15 cases.

One patient was not included for two reasons (Parent's decision and other reason)

Arm/Group Title Placebo Propranolol 1mg/kg/d 3 Months Propranolol 1 mg/kg/d 6 Months Propranolol 3 mg/kg/d 3 Months Propranolol 3 mg/kg/d 6 Months
Hide Arm/Group Description Placebo: Treatment with placebo for 6 months Propranolol oral solution 1mg/kg/day for 3 months, then placebo for 3 months Propranolol oral solution 1mg/kg/day for 6 months Propranolol oral solution 3mg/kg/day for 3 months, then placebo for 3 months Propranolol oral solution 3mg/kg/day for 6 months
Period Title: Overall Study
Started 55 99 103 101 102
Interim Analysis 25 41 41 40 43
Completed 19 63 88 65 88
Not Completed 36 36 15 36 14
Reason Not Completed
Treatment Intolerance             0             2             0             2             0
Lack of Efficacy             32             30             7             25             9
Other reasons             4             4             8             9             5
Arm/Group Title Placebo Propranolol 1mg/kg/d 3 Months Propranolol 1 mg/kg/d 6 Months Propranolol 3 mg/kg/d 3 Months Propranolol 3 mg/kg/d 6 Months Total
Hide Arm/Group Description Placebo: Treatment with placebo for 6 months Propranolol oral solution 1mg/kg/day for 3 months, then placebo for 3 months Propranolol oral solution 1mg/kg/day for 6 months Propranolol oral solution 3mg/kg/day for 3 months, then placebo for 3 months Propranolol oral solution 3mg/kg/day for 6 months Total of all reporting groups
Overall Number of Baseline Participants 55 98 102 100 101 456
Hide Baseline Analysis Population Description
Among the 460 randomized patients, 4 were not treated: 2 because of parent(s)'/guardian's decision (1 in 1mg/kg/day 6 months arm,1 in 3 mg/kg/day 3 months arm), 2 because of absence of adequate treatment on site (1 in 1 mg/kg/day 3 months arm and 1 in 3mg/kg/day 6 months arm).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  DAYS
Number Analyzed 55 participants 98 participants 102 participants 100 participants 101 participants 456 participants
103.91  (31.06) 103.58  (33.07) 102.65  (30.12) 107.53  (30.14) 101.63  (31.00) 103.85  (31.02)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants 98 participants 102 participants 100 participants 101 participants 456 participants
Female
38
  69.1%
68
  69.4%
70
  68.6%
79
  79.0%
70
  69.3%
325
  71.3%
Male
17
  30.9%
30
  30.6%
32
  31.4%
21
  21.0%
31
  30.7%
131
  28.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 55 participants 98 participants 102 participants 100 participants 101 participants 456 participants
United States 6 13 13 11 10 53
Spain 5 9 14 17 14 59
Lithuania 1 7 4 1 5 18
Russian Federation 0 1 0 1 1 3
Italy 1 0 0 0 1 2
France 21 25 18 22 28 114
Czech Republic 2 1 3 1 1 8
Hungary 1 2 4 2 2 11
Mexico 0 2 0 3 0 5
Canada 2 5 6 3 2 18
Poland 4 4 6 8 4 26
Romania 2 2 1 0 2 7
Peru 1 5 9 8 12 35
Australia 1 5 14 5 7 32
Germany 8 17 9 17 9 60
New Zealand 0 0 1 1 3 5
Infantile hemangioma localization  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 55 participants 98 participants 102 participants 100 participants 101 participants 456 participants
FACE 40 71 72 64 71 318
NONE FACE 15 27 30 36 30 138
1.Primary Outcome
Title Interim Analysis : Complete/Nearly Complete Resolution of the Target Infantile Hemangioma at Week 24 Compared to Baseline Based on the Intra-patient Blinded Centralized Independent Qualitative Assessments of Week 24 Photographs.
Hide Description [Not Specified]
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Among the 190 first randomized patients who entered the stage 1 of the study, 2 patients were not treated because of parent'/legal guardian's decision: 1 in the 1mg/kg/day 6 months arm and 1 in the 3 mg/kg/day 3 months arm.
Arm/Group Title Placebo Propranolol 1mg/kg/d 3 Months Propranolol 1 mg/kg/d 6 Months Propranolol 3 mg/kg/d 3 Months Propranolol 3 mg/kg/d 6 Months
Hide Arm/Group Description:
Placebo: Treatment with placebo for 6 months
Propranolol oral solution 1mg/kg/day for 3 months, then placebo for 3 months
Propranolol oral solution 1mg/kg/day for 6 months
Propranolol oral solution 3mg/kg/day for 3 months, then placebo for 3 months
Propranolol oral solution 3mg/kg/day for 6 months
Overall Number of Participants Analyzed 25 41 40 39 43
Measure Type: Number
Unit of Measure: percentage of participants
8.0 9.8 37.5 7.7 62.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Propranolol 1mg/kg/d 3 Months, Propranolol 1 mg/kg/d 6 Months, Propranolol 3 mg/kg/d 3 Months, Propranolol 3 mg/kg/d 6 Months
Comments The interim analysis was carried out after the first 188 patients have completed their W24 visit or been withdrawn prematurely from study therapy. For each propranolol arm, individual hypotheses H0,i: θi≤0
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments

P-value not adjusted for multiplicity. An Independent Committee conducted this analysis to determine the most efficacious of all arms with a good safety profile.

P-value linked to the 3 mg/kg/day 6 months selected arm .

Method One-sided Z-tests
Comments One-sided Z-tests for proportions (contrasts tests on placebo) with pooled variance
2.Primary Outcome
Title Primary Analysis : Complete/Nearly Complete Resolution of the Target Infantile Hemangioma at W24 Compared to Baseline Based on the Intra-patient Blinded Centralized Independent Qualitative Assessments of W24 Photographs.
Hide Description [Not Specified]
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
After the interim analysis results, the Independent Committee recommendations was to continue the trial with the 3 mg/kg/day6 months arm and the placebo arm. 55 randomized and treated patients in the placebo arm and 102 randomized patients in the 3 mg/kg/day6 months arm,1 was not treated because no unit of the assigned treatment available on site.
Arm/Group Title Placebo Propranolol 3mg/kg/d 6 Months
Hide Arm/Group Description:
Placebo: Treatment with placebo for 6 months
Propranolol 3 mg/kg/day for 6 months
Overall Number of Participants Analyzed 55 101
Measure Type: Number
Unit of Measure: percentage of participants
3.6 60.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Propranolol 3mg/kg/d 6 Months
Comments

The objective is to test the superiority of the selected arm using the approach of Posch et al.

The primary analysis was performed on the intent-to-treat population: all treated patients in Stage 1 and all treated patients in stage 2 randomized to placebo or the selected arm.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The methodology used guaranteed that the familywise type I error rate was below the nominal one-sided significance level of 0.005.
Method combination tests
Comments Superiority was tested using the closed testing procedure and combination tests for all intersection hypotheses using Simes’ adjustment.
3.Secondary Outcome
Title Success/Failure Based on the Investigator Qualitative Assessment of Complete Resolution at W48.
Hide Description Time to first sustained improvement based on centralized qualitative assessments of paired patient-visits
Time Frame 6 months
Outcome Measure Data Not Reported
Time Frame Safety evaluation of the four regimens of oral propranolol (versus placebo) over a 24-week treatment period. Safety evaluation of the four previous regimens of oral propranolol (versus placebo) over a follow up period of 72 weeks (up to 96 weeks).
Adverse Event Reporting Description

Safety population included all participants who received at least one dose of Propranolol (1 or 3mg/kg/day for 3 or 6 months) or placebo.

Among the 456 treated patients, 65 were withdrawn during treatment period:22 in placebo arm, 13 in 1mg/kg/day 3months arm, 11 in 1mg/kg/day 6months arm, 13 in 3mg/kg/day 3months arm, 6 in 3mg/kg/day 6months arm.

 
Arm/Group Title W24-treatment Period-safety Set-Placebo W24-treatment Period-safety Set-Propranolol 1mg/kg/d 3 Months W24-treatment Period-safety Set-Propranolol 1 mg/kg/d 6 Months W24-treatment Period-safety Set-Propranolol 3 mg/kg/d 3 Months W24-treatment Period-safety Set-Propranolol 3 mg/kg/d 6 Months W72-follow-up Period of ex Placebo Group-safety Set W72-follow-up Period of ex 1mg/kg/d 3 Months Group-safety Set W72-follow-up Period of ex 1mg/kg/d 6 Months Group-safety Set W72-follow-up Period of ex 3mg/kg/d 3 Months Group-safety Set W72-follow-up Period of ex 3mg/kg/d 6 Months Group-safety Set
Hide Arm/Group Description Placebo: Treatment with placebo for 6 months Propranolol hydrochloride oral solution 1mg/kg/day for 3 months, then placebo for 3 months Propranolol hydrochloride oral solution 1mg/kg/day for 6 months Propranolol hydrochloride oral solution 3mg/kg/day for 3 months, then placebo for 3 months Propranolol hydrochloride oral solution 3mg/kg/day for 6 months 72-week follow-up period without study treatment administration 72-week follow-up period without study treatment administration 72-week follow-up period without study treatment administration 72-week follow-up period without study treatment administration 72-week follow-up period without study treatment administration
All-Cause Mortality
W24-treatment Period-safety Set-Placebo W24-treatment Period-safety Set-Propranolol 1mg/kg/d 3 Months W24-treatment Period-safety Set-Propranolol 1 mg/kg/d 6 Months W24-treatment Period-safety Set-Propranolol 3 mg/kg/d 3 Months W24-treatment Period-safety Set-Propranolol 3 mg/kg/d 6 Months W72-follow-up Period of ex Placebo Group-safety Set W72-follow-up Period of ex 1mg/kg/d 3 Months Group-safety Set W72-follow-up Period of ex 1mg/kg/d 6 Months Group-safety Set W72-follow-up Period of ex 3mg/kg/d 3 Months Group-safety Set W72-follow-up Period of ex 3mg/kg/d 6 Months Group-safety Set
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
W24-treatment Period-safety Set-Placebo W24-treatment Period-safety Set-Propranolol 1mg/kg/d 3 Months W24-treatment Period-safety Set-Propranolol 1 mg/kg/d 6 Months W24-treatment Period-safety Set-Propranolol 3 mg/kg/d 3 Months W24-treatment Period-safety Set-Propranolol 3 mg/kg/d 6 Months W72-follow-up Period of ex Placebo Group-safety Set W72-follow-up Period of ex 1mg/kg/d 3 Months Group-safety Set W72-follow-up Period of ex 1mg/kg/d 6 Months Group-safety Set W72-follow-up Period of ex 3mg/kg/d 3 Months Group-safety Set W72-follow-up Period of ex 3mg/kg/d 6 Months Group-safety Set
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/55 (5.45%)      5/98 (5.10%)      3/102 (2.94%)      9/100 (9.00%)      5/101 (4.95%)      5/33 (15.15%)      6/85 (7.06%)      5/91 (5.49%)      5/87 (5.75%)      7/95 (7.37%)    
Cardiac disorders                     
Atrioventricular block second degree  0/55 (0.00%)  1/98 (1.02%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
Bradycardia  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  1/100 (1.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
Cyanosis  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  1/100 (1.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
Congenital, familial and genetic disorders                     
hip dysplasia  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  1/85 (1.18%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
Gastrointestinal disorders                     
Enterocolitis  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  1/100 (1.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
Gastrooesophageal reflux disease  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  2/100 (2.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
General disorders                     
Condition aggravated  2/55 (3.64%)  0/98 (0.00%)  0/102 (0.00%)  1/100 (1.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
Drug ineffective  1/55 (1.82%)  1/98 (1.02%)  0/102 (0.00%)  0/100 (0.00%)  1/101 (0.99%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
Pyrexia  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  1/95 (1.05%) 
inflammation  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  1/95 (1.05%) 
hyperthermia  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  1/87 (1.15%)  0/95 (0.00%) 
Infections and infestations                     
Bronchiolitis  0/55 (0.00%)  1/98 (1.02%)  0/102 (0.00%)  1/100 (1.00%)  1/101 (0.99%)  1/33 (3.03%)  0/85 (0.00%)  0/91 (0.00%)  1/87 (1.15%)  2/95 (2.11%) 
Bronchitis  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  1/100 (1.00%)  1/101 (0.99%)  1/33 (3.03%)  1/85 (1.18%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
Bronchopneumonia  0/55 (0.00%)  0/98 (0.00%)  1/102 (0.98%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
Cystitis  0/55 (0.00%)  1/98 (1.02%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
Gastroenteritis  0/55 (0.00%)  0/98 (0.00%)  1/102 (0.98%)  0/100 (0.00%)  0/101 (0.00%)  1/33 (3.03%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  1/95 (1.05%) 
Pyelonephritis  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  1/100 (1.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  1/95 (1.05%) 
Rotavirus infection  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  1/100 (1.00%)  0/101 (0.00%)  0/33 (0.00%)  1/85 (1.18%)  0/91 (0.00%)  2/87 (2.30%)  0/95 (0.00%) 
Viraemia  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  1/100 (1.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
respiratory tract infection viral  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  1/95 (1.05%) 
ear infection  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  1/87 (1.15%)  0/95 (0.00%) 
gastroenteritis rotavirus  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  1/91 (1.10%)  0/87 (0.00%)  0/95 (0.00%) 
nasopharyngitis  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  1/87 (1.15%)  0/95 (0.00%) 
otitis media acute  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  1/33 (3.03%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
respiratory syncytial virus infection  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  1/33 (3.03%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
tonsillitis  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  1/91 (1.10%)  0/87 (0.00%)  0/95 (0.00%) 
pneumonia  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  2/85 (2.35%)  0/91 (0.00%)  0/87 (0.00%)  1/95 (1.05%) 
Injury, poisoning and procedural complications                     
Traumatic brain injury  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/101 (0.99%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
Metabolism and nutrition disorders                     
dehydration  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  1/100 (1.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  1/91 (1.10%)  0/87 (0.00%)  0/95 (0.00%) 
ketoacidosis  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  1/91 (1.10%)  0/87 (0.00%)  0/95 (0.00%) 
type 1 diabetes mellitus  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  1/91 (1.10%)  0/87 (0.00%)  0/95 (0.00%) 
Nervous system disorders                     
Epilepsy  0/55 (0.00%)  0/98 (0.00%)  1/102 (0.98%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
convulsion  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  1/87 (1.15%)  0/95 (0.00%) 
febrile convulsion  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  1/85 (1.18%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
Psychiatric disorders                     
Apathy  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  1/100 (1.00%)  1/101 (0.99%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
Respiratory, thoracic and mediastinal disorders                     
asphyxia  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  1/85 (1.18%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
asthma  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  1/91 (1.10%)  0/87 (0.00%)  0/95 (0.00%) 
cough  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  1/87 (1.15%)  0/95 (0.00%) 
Surgical and medical procedures                     
Ileostomy closure  0/55 (0.00%)  0/98 (0.00%)  1/102 (0.98%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
Inguinal hernia repair  0/55 (0.00%)  0/98 (0.00%)  1/102 (0.98%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
cataract operation  0/55 (0.00%)  1/98 (1.02%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
surgery  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  1/85 (1.18%)  0/91 (0.00%)  0/87 (0.00%)  1/95 (1.05%) 
Finger amputation  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  1/85 (1.18%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
hip surgery  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  1/85 (1.18%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
hospitalisation  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  1/87 (1.15%)  0/95 (0.00%) 
scrotal operation  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  1/33 (3.03%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
W24-treatment Period-safety Set-Placebo W24-treatment Period-safety Set-Propranolol 1mg/kg/d 3 Months W24-treatment Period-safety Set-Propranolol 1 mg/kg/d 6 Months W24-treatment Period-safety Set-Propranolol 3 mg/kg/d 3 Months W24-treatment Period-safety Set-Propranolol 3 mg/kg/d 6 Months W72-follow-up Period of ex Placebo Group-safety Set W72-follow-up Period of ex 1mg/kg/d 3 Months Group-safety Set W72-follow-up Period of ex 1mg/kg/d 6 Months Group-safety Set W72-follow-up Period of ex 3mg/kg/d 3 Months Group-safety Set W72-follow-up Period of ex 3mg/kg/d 6 Months Group-safety Set
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   40/55 (72.73%)      88/98 (89.80%)      92/102 (90.20%)      92/100 (92.00%)      96/101 (95.05%)      27/33 (81.82%)      66/85 (77.65%)      70/91 (76.92%)      65/87 (74.71%)      75/95 (78.95%)    
Eye disorders                     
Conjunctivitis  2/55 (3.64%)  4/98 (4.08%)  8/102 (7.84%)  2/100 (2.00%)  8/101 (7.92%)  1/33 (3.03%)  7/85 (8.24%)  8/91 (8.79%)  7/87 (8.05%)  9/95 (9.47%) 
Gastrointestinal disorders                     
Constipation  1/55 (1.82%)  9/98 (9.18%)  6/102 (5.88%)  9/100 (9.00%)  4/101 (3.96%)  1/33 (3.03%)  1/85 (1.18%)  4/91 (4.40%)  0/87 (0.00%)  1/95 (1.05%) 
Diarrhea  4/55 (7.27%)  16/98 (16.33%)  14/102 (13.73%)  17/100 (17.00%)  28/101 (27.72%)  51 1/33 (3.03%)  4/85 (4.71%)  4/91 (4.40%)  10/87 (11.49%)  9/95 (9.47%) 
Teething  6/55 (10.91%)  19/98 (19.39%)  23/102 (22.55%)  16/100 (16.00%)  22/101 (21.78%)  0/33 (0.00%)  5/85 (5.88%)  9/91 (9.89%)  7/87 (8.05%)  8/95 (8.42%) 
Toothhache  2/55 (3.64%)  5/98 (5.10%)  2/102 (1.96%)  8/100 (8.00%)  10/101 (9.90%)  0/33 (0.00%)  1/85 (1.18%)  0/91 (0.00%)  0/87 (0.00%)  4/95 (4.21%) 
Vomiting  3/55 (5.45%)  16/98 (16.33%)  13/102 (12.75%)  10/100 (10.00%)  13/101 (12.87%)  2/33 (6.06%)  3/85 (3.53%)  3/91 (3.30%)  4/87 (4.60%)  2/95 (2.11%) 
gingival pain  1/55 (1.82%)  3/98 (3.06%)  0/102 (0.00%)  5/100 (5.00%)  2/101 (1.98%)  1/33 (3.03%)  1/85 (1.18%)  0/91 (0.00%)  1/87 (1.15%)  0/95 (0.00%) 
General disorders                     
Irritability  3/55 (5.45%)  5/98 (5.10%)  6/102 (5.88%)  1/100 (1.00%)  2/101 (1.98%)  0/33 (0.00%)  0/85 (0.00%)  1/91 (1.10%)  0/87 (0.00%)  0/95 (0.00%) 
Pyrexia  6/55 (10.91%)  21/98 (21.43%)  24/102 (23.53%)  22/100 (22.00%)  28/101 (27.72%)  6/33 (18.18%)  21/85 (24.71%)  15/91 (16.48%)  20/87 (22.99%)  24/95 (25.26%) 
condition aggravated  0/55 (0.00%)  3/98 (3.06%)  1/102 (0.98%)  3/100 (3.00%)  2/101 (1.98%)  2/33 (6.06%)  1/85 (1.18%)  1/91 (1.10%)  1/87 (1.15%)  3/95 (3.16%) 
Infections and infestations                     
Bronchiolitis  3/55 (5.45%)  5/98 (5.10%)  7/102 (6.86%)  5/100 (5.00%)  9/101 (8.91%)  2/33 (6.06%)  6/85 (7.06%)  4/91 (4.40%)  9/87 (10.34%)  11/95 (11.58%) 
Bronchitis  1/55 (1.82%)  5/98 (5.10%)  8/102 (7.84%)  10/100 (10.00%)  16/101 (15.84%)  3/33 (9.09%)  12/85 (14.12%)  14/91 (15.38%)  18/87 (20.69%)  20/95 (21.05%) 
Ear infection  0/55 (0.00%)  7/98 (7.14%)  6/102 (5.88%)  7/100 (7.00%)  4/101 (3.96%)  6/33 (18.18%)  13/85 (15.29%)  13/91 (14.29%)  14/87 (16.09%)  17/95 (17.89%) 
Gastroenteritis  2/55 (3.64%)  2/98 (2.04%)  5/102 (4.90%)  4/100 (4.00%)  11/101 (10.89%)  4/33 (12.12%)  7/85 (8.24%)  9/91 (9.89%)  14/87 (16.09%)  14/95 (14.74%) 
Nasopharyngitis  10/55 (18.18%)  29/98 (29.59%)  21/102 (20.59%)  32/100 (32.00%)  34/101 (33.66%)  8/33 (24.24%)  26/85 (30.59%)  20/91 (21.98%)  24/87 (27.59%)  30/95 (31.58%) 
Rhinitis  5/55 (9.09%)  13/98 (13.27%)  13/102 (12.75%)  5/100 (5.00%)  5/101 (4.95%)  3/33 (9.09%)  9/85 (10.59%)  7/91 (7.69%)  1/87 (1.15%)  6/95 (6.32%) 
Upper respiratory tract infection  4/55 (7.27%)  6/98 (6.12%)  13/102 (12.75%)  20/100 (20.00%)  16/101 (15.84%)  5/33 (15.15%)  7/85 (8.24%)  15/91 (16.48%)  13/87 (14.94%)  11/95 (11.58%) 
tonsillitis  0/55 (0.00%)  1/98 (1.02%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  3/33 (9.09%)  7/85 (8.24%)  6/91 (6.59%)  7/87 (8.05%)  10/95 (10.53%) 
pharyngitis  0/55 (0.00%)  4/98 (4.08%)  3/102 (2.94%)  2/100 (2.00%)  3/101 (2.97%)  0/33 (0.00%)  5/85 (5.88%)  4/91 (4.40%)  6/87 (6.90%)  8/95 (8.42%) 
otite media  0/55 (0.00%)  1/98 (1.02%)  1/102 (0.98%)  3/100 (3.00%)  2/101 (1.98%)  6/33 (18.18%)  5/85 (5.88%)  4/91 (4.40%)  4/87 (4.60%)  5/95 (5.26%) 
influenza  1/55 (1.82%)  1/98 (1.02%)  3/102 (2.94%)  3/100 (3.00%)  4/101 (3.96%)  1/33 (3.03%)  2/85 (2.35%)  0/91 (0.00%)  2/87 (2.30%)  5/95 (5.26%) 
varicella  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  2/33 (6.06%)  5/85 (5.88%)  4/91 (4.40%)  6/87 (6.90%)  4/95 (4.21%) 
roseola  1/55 (1.82%)  1/98 (1.02%)  0/102 (0.00%)  2/100 (2.00%)  0/101 (0.00%)  1/33 (3.03%)  3/85 (3.53%)  5/91 (5.49%)  1/87 (1.15%)  4/95 (4.21%) 
hand-foot-and-mouth disease  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  0/101 (0.00%)  2/33 (6.06%)  1/85 (1.18%)  2/91 (2.20%)  3/87 (3.45%)  3/95 (3.16%) 
acute tonsillitis  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  2/101 (1.98%)  2/33 (6.06%)  1/85 (1.18%)  0/91 (0.00%)  1/87 (1.15%)  2/95 (2.11%) 
croup infectious  0/55 (0.00%)  1/98 (1.02%)  1/102 (0.98%)  0/100 (0.00%)  1/101 (0.99%)  2/33 (6.06%)  1/85 (1.18%)  1/91 (1.10%)  1/87 (1.15%)  1/95 (1.05%) 
eye infection  1/55 (1.82%)  0/98 (0.00%)  1/102 (0.98%)  0/100 (0.00%)  0/101 (0.00%)  3/33 (9.09%)  0/85 (0.00%)  0/91 (0.00%)  1/87 (1.15%)  0/95 (0.00%) 
gastroenteritis viral  0/55 (0.00%)  0/98 (0.00%)  0/102 (0.00%)  0/100 (0.00%)  1/101 (0.99%)  2/33 (6.06%)  1/85 (1.18%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
Injury, poisoning and procedural complications                     
Vaccination complication  2/55 (3.64%)  7/98 (7.14%)  9/102 (8.82%)  8/100 (8.00%)  8/101 (7.92%)  1/33 (3.03%)  1/85 (1.18%)  1/91 (1.10%)  2/87 (2.30%)  2/95 (2.11%) 
Metabolism and nutrition disorders                     
decreased appetite  1/55 (1.82%)  5/98 (5.10%)  3/102 (2.94%)  5/100 (5.00%)  1/101 (0.99%)  0/33 (0.00%)  0/85 (0.00%)  1/91 (1.10%)  0/87 (0.00%)  1/95 (1.05%) 
Nervous system disorders                     
Somnolence  1/55 (1.82%)  6/98 (6.12%)  4/102 (3.92%)  1/100 (1.00%)  1/101 (0.99%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
hypotonia  0/55 (0.00%)  1/98 (1.02%)  1/102 (0.98%)  0/100 (0.00%)  0/101 (0.00%)  2/33 (6.06%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
Psychiatric disorders                     
Insomnia  3/55 (5.45%)  3/98 (3.06%)  1/102 (0.98%)  3/100 (3.00%)  3/101 (2.97%)  1/33 (3.03%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
Middle insomnia  3/55 (5.45%)  6/98 (6.12%)  4/102 (3.92%)  7/100 (7.00%)  6/101 (5.94%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  1/95 (1.05%) 
Sleep disorder  1/55 (1.82%)  12/98 (12.24%)  6/102 (5.88%)  1/100 (1.00%)  7/101 (6.93%)  1/33 (3.03%)  1/85 (1.18%)  0/91 (0.00%)  1/87 (1.15%)  1/95 (1.05%) 
agitation  0/55 (0.00%)  1/98 (1.02%)  6/102 (5.88%)  3/100 (3.00%)  0/101 (0.00%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
Respiratory, thoracic and mediastinal disorders                     
Cough  4/55 (7.27%)  14/98 (14.29%)  18/102 (17.65%)  16/100 (16.00%)  14/101 (13.86%)  4/33 (12.12%)  8/85 (9.41%)  5/91 (5.49%)  7/87 (8.05%)  7/95 (7.37%) 
Rhinorrhea  2/55 (3.64%)  3/98 (3.06%)  3/102 (2.94%)  8/100 (8.00%)  3/101 (2.97%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  3/87 (3.45%)  5/95 (5.26%) 
nasal congestion  1/55 (1.82%)  3/98 (3.06%)  6/102 (5.88%)  4/100 (4.00%)  4/101 (3.96%)  0/33 (0.00%)  1/85 (1.18%)  1/91 (1.10%)  0/87 (0.00%)  1/95 (1.05%) 
asthma  0/55 (0.00%)  0/98 (0.00%)  1/102 (0.98%)  1/100 (1.00%)  2/101 (1.98%)  0/33 (0.00%)  2/85 (2.35%)  3/91 (3.30%)  5/87 (5.75%)  5/95 (5.26%) 
Skin and subcutaneous tissue disorders                     
Dermatitis diaper  2/55 (3.64%)  4/98 (4.08%)  5/102 (4.90%)  4/100 (4.00%)  9/101 (8.91%)  1/33 (3.03%)  4/85 (4.71%)  2/91 (2.20%)  3/87 (3.45%)  3/95 (3.16%) 
Eczema  1/55 (1.82%)  8/98 (8.16%)  4/102 (3.92%)  2/100 (2.00%)  2/101 (1.98%)  2/33 (6.06%)  4/85 (4.71%)  2/91 (2.20%)  4/87 (4.60%)  4/95 (4.21%) 
dermatitis atopic  1/55 (1.82%)  2/98 (2.04%)  1/102 (0.98%)  1/100 (1.00%)  3/101 (2.97%)  2/33 (6.06%)  0/85 (0.00%)  0/91 (0.00%)  2/87 (2.30%)  2/95 (2.11%) 
Vascular disorders                     
Peripheral coldness  1/55 (1.82%)  8/98 (8.16%)  10/102 (9.80%)  1/100 (1.00%)  10/101 (9.90%)  0/33 (0.00%)  0/85 (0.00%)  0/91 (0.00%)  0/87 (0.00%)  0/95 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.

The investigators can reserve the right to publish or present study data; provided that the sponsor reviews the abstract or manuscript at least 60 days prior to the expected date of submission to the intended publisher or planned presentation.

Publication of study results by each site shall be made only after completion and finalisation of the study by all sites and first publication by the Sponsor.

Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Jean-Jacques VOISARD - General Manager -
Organization: Pierre Fabre Dermatologie
Phone: +33 5 63 58 88 00
EMail: jean.jacques.voisard@pierre-fabre.com
Layout table for additonal information
Responsible Party: Pierre Fabre Dermatology
ClinicalTrials.gov Identifier: NCT01056341     History of Changes
Other Study ID Numbers: V00400 SB 201 Study
First Submitted: January 24, 2010
First Posted: January 26, 2010
Results First Submitted: April 9, 2014
Results First Posted: June 24, 2014
Last Update Posted: December 10, 2015