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Trial record 37 of 116 for:    Atenolol

Comparison of Two Medications Aimed at Slowing Aortic Root Enlargement in Individuals With Marfan Syndrome--Pediatric Heart Network

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ClinicalTrials.gov Identifier: NCT00429364
Recruitment Status : Completed
First Posted : January 31, 2007
Results First Posted : April 1, 2015
Last Update Posted : April 1, 2015
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
FDA Office of Orphan Products Development
National Marfan Foundation
Information provided by (Responsible Party):
New England Research Institutes

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Treatment
Condition Marfan Syndrome
Interventions Drug: Losartan Potassium
Drug: Atenolol
Enrollment 608
Recruitment Details From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants into the study.
Pre-assignment Details For subjects on prophylactic therapy with atenolol or other BB, ARB, ACEi, or calcium-channel blocker, before the study, the drug will be weaned over a 14-day period. After that, a drug washout period of 14–21 days will take place before baseline assessment and randomization.
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate. Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Period Title: Overall Study
Started 303 305
Completed 271 272
Not Completed 32 33
Reason Not Completed
Withdrawal by Subject             11             5
Physician Decision             4             2
Lost to Follow-up             7             6
Death             0             1
Underwent aortic root surgery             10             18
Pregnancy             0             1
Arm/Group Title Atenolol Losartan Total
Hide Arm/Group Description Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate. Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg). Total of all reporting groups
Overall Number of Baseline Participants 303 305 608
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 303 participants 305 participants 608 participants
11.5  (6.5) 11.0  (6.2) 11.2  (6.3)
Age, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 303 participants 305 participants 608 participants
Young adult 76 75 151
Child 227 230 457
[1]
Measure Description: Young adults were defined as male participants who were 16 to 25 years of age and female participants who were 15 to 25 years of age.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 303 participants 305 participants 608 participants
Female
123
  40.6%
119
  39.0%
242
  39.8%
Male
180
  59.4%
186
  61.0%
366
  60.2%
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 303 participants 305 participants 608 participants
Hispanic or Latino
36
  11.9%
46
  15.1%
82
  13.5%
Not Hispanic or Latino
266
  87.8%
259
  84.9%
525
  86.3%
Unknown or Not Reported
1
   0.3%
0
   0.0%
1
   0.2%
[1]
Measure Description: Data on race and ethnicity provided by the participant or a family member at the time of enrollment.
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 303 participants 305 participants 608 participants
White 266 260 526
Black 21 25 46
Asian 6 10 16
Other 10 10 20
[1]
Measure Description: Data on race and ethnicity provided by the participant or a family member at the time of enrollment.
Presence of causal FBN1 mutation  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 303 participants 305 participants 608 participants
Yes 93 88 181
No 9 15 24
Unknown 201 202 403
Family history of Marfan  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 303 participants 305 participants 608 participants
Yes 180 181 361
No 115 109 224
Unknown 8 15 23
Maximum aortic-root diameter, cm   [1] 
Mean (Standard Deviation)
Unit of measure:  Centimeter
Number Analyzed 303 participants 305 participants 608 participants
3.4  (0.7) 3.4  (0.7) 3.4  (0.7)
[1]
Measure Description: Data are based on readings at a central echocardiographic laboratory. Echocardiographic data were missing for one participant in the losartan group because of an unreadable echocardiogram.
Maximum aortic-root diameter z-score   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Z-score
Number Analyzed 303 participants 305 participants 608 participants
4.0
(3.5 to 4.8)
4.0
(3.3 to 5.0)
4.0
(3.4 to 4.9)
[1]
Measure Description: Data are based on readings at a central echocardiographic laboratory. Echocardiographic data were missing for one participant in the losartan group because of an unreadable echocardiogram.
Maximum aortic-root diameter z-score   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 303 participants 305 participants 608 participants
≥z-score of 4.5 106 114 220
<z-score of 4.5 197 191 388
[1]
Measure Description: Data are based on readings at a central echocardiographic laboratory. Echocardiographic data were missing for one participant in the losartan group because of an unreadable echocardiogram.
Had medical history of cardiac surgery  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 303 participants 305 participants 608 participants
Yes 6 6 12
No 297 299 596
Had medical history of cardiovascular disorder   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 303 participants 305 participants 608 participants
Yes 39 36 75
No 264 269 533
[1]
Measure Description: Cardiovascular disorder was defined by exercise intolerance, syncope; arrhythmia, hypertension, or hypotension requiring therapy; chest pain, shortness of breath; or other cardiovascular conditions.
Prior use of beta-blocker  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 303 participants 305 participants 608 participants
Yes 173 171 344
No 130 134 264
Had medical history of endocrine disorder   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 303 participants 305 participants 608 participants
Yes 7 0 7
No 296 305 601
[1]
Measure Description: Endocrine disorder was defined by either the use of hormone therapy to limit growth, delayed puberty.
Had medical history of neurodevelopmental disorder   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 303 participants 305 participants 608 participants
Yes 56 61 117
No 247 244 491
[1]
Measure Description: Neurodevelopmental disorder was defined as attention deficit-hyperactivity disorder requiring therapy, developmental delay requiring therapy, learning disability requiring services, or other neurodevelopmental conditions.
Had medical history of psychiatric disorder   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 303 participants 305 participants 608 participants
Yes 23 16 39
No 280 289 569
[1]
Measure Description: Psychiatric disorder was defined as depression requiring therapy, anxiety, or other psychiatric conditions.
1.Primary Outcome
Title Annual Rate of Change in Aortic Root (Sinuses of Valsalva) Body-surface-area-adjusted Z-score
Hide Description The rate of aortic root enlargement, expressed as the annual change in the maximum aortic-root-diameter z score indexed to body-surface area over a 3-year period following randomization
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 303 305
Least Squares Mean (Standard Error)
Unit of Measure: z-score/year
-0.139  (0.013) -0.107  (0.013)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atenolol, Losartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.08
Comments P values are based on a linear regression mixed-effect model comparing slopes under compound symmetry, with adjustment for baseline.
Method Mixed Models Analysis
Comments [Not Specified]
2.Secondary Outcome
Title Annual Rate of Change in Aortic Root (Sinuses of Valsalva) Absolute Dimension
Hide Description The rate of change in the absolute dimension of the aortic root over a 3-year period following randomization
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 303 305
Least Squares Mean (Standard Error)
Unit of Measure: cm/year
0.069  (0.004) 0.075  (0.004)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atenolol, Losartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.20
Comments P values are based on a linear regression mixed-effect model comparing slopes under compound symmetry, with adjustment for baseline.
Method Mixed Models Analysis
Comments [Not Specified]
3.Secondary Outcome
Title Annual Rate of Change in Ascending-aorta-diameter Z Score, Adjusted by Body-surface-area.
Hide Description [Not Specified]
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants whose ascending-aorta-diameter z scores were measured at baseline and at any of the follow-up visits.
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 296 303
Least Squares Mean (Standard Error)
Unit of Measure: z-score/year
-0.140  (0.013) -0.114  (0.013)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atenolol, Losartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments P values are based on a linear regression mixed-effect model comparing slopes under compound symmetry, with adjustment for baseline.
Method Mixed Models Analysis
Comments [Not Specified]
4.Secondary Outcome
Title Annual Rate of Change in the Absolute Diameter of the Ascending Aorta
Hide Description [Not Specified]
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants whose absolute dimensions of the ascending aorta were measured at baseline and at any of the follow-up visits.
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 296 303
Least Squares Mean (Standard Error)
Unit of Measure: cm/year
0.039  (0.004) 0.044  (0.004)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atenolol, Losartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.30
Comments P values are based on a linear regression mixed-effect model comparing slopes under compound symmetry, with adjustment for baseline.
Method Mixed Models Analysis
Comments [Not Specified]
5.Secondary Outcome
Title Annual Rate of Change in Aortic-annulus-diameter Z Score, Adjusted by Body-surface Area
Hide Description [Not Specified]
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants whose aortic-annulus-diameter z scores were measured at baseline and at any of the follow-up visits.
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 302 304
Least Squares Mean (Standard Error)
Unit of Measure: z-score/year
-0.279  (0.018) -0.175  (0.018)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atenolol, Losartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P values are based on a linear regression mixed-effect model comparing slopes under compound symmetry, with adjustment for baseline.
Method Mixed Models Analysis
Comments [Not Specified]
6.Secondary Outcome
Title Annual Rate of Change in the Absolute Diameter of the Aortic Annulus
Hide Description [Not Specified]
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants whose absolute dimensions of the aortic annulus were measured at baseline and at any of the follow-up visits.
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 302 304
Least Squares Mean (Standard Error)
Unit of Measure: cm/year
0.015  (0.003) 0.030  (0.003)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atenolol, Losartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments P values are based on a linear regression mixed-effect model comparing slopes under compound symmetry, with adjustment for baseline.
Method Mixed Models Analysis
Comments [Not Specified]
7.Secondary Outcome
Title Annual Rate of Change in Total Aortic Proximal Regurgitant Jet Area Indexed to Body-surface-area
Hide Description [Not Specified]
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants whose total aortic proximal regurgitant jet area indexes were measured at baseline or at any of the follow-up visits.
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 301 303
Least Squares Mean (Standard Error)
Unit of Measure: (mm^2/m^2)/year
0.005  (0.003) 0.001  (0.003)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atenolol, Losartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.29
Comments P values are based on a linear regression mixed-effect model comparing slopes under compound symmetry, with adjustment for baseline.
Method Mixed Models Analysis
Comments [Not Specified]
8.Secondary Outcome
Title Annual Rate of Change in Weight
Hide Description [Not Specified]
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 303 305
Least Squares Mean (Standard Error)
Unit of Measure: kg/year
0.239  (0.153) 0.229  (0.154)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atenolol, Losartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.96
Comments Regression model adjusted for age at study visit.
Method Mixed Models Analysis
Comments [Not Specified]
9.Secondary Outcome
Title Annual Rate of Change in Weight-for-age Z-score
Hide Description [Not Specified]
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who were between 0-20 years of age and whose weight-for-age z-scores were measured at baseline and at any of the follow-up visits.
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 270 278
Least Squares Mean (Standard Error)
Unit of Measure: z-score/year
0.011  (0.013) 0.019  (0.013)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atenolol, Losartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.45
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
10.Secondary Outcome
Title Annual Rate of Change in Weight-for-height Z-score
Hide Description [Not Specified]
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who were <120 cm in heights and whose weight-for-height z-scores were measured at baseline or at any of the follow-up visits.
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 58 61
Least Squares Mean (Standard Error)
Unit of Measure: z-score/year
-0.001  (0.072) -0.157  (0.076)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atenolol, Losartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.13
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
11.Secondary Outcome
Title Annual Rate of Change in Height
Hide Description [Not Specified]
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants whose heights were measured at baseline and at any of the follow-up visits.
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 303 305
Least Squares Mean (Standard Error)
Unit of Measure: cm/year
0.822  (0.204) 0.935  (0.202)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atenolol, Losartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.65
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
12.Secondary Outcome
Title Annual Rate of Change in Height-for-age Z-score
Hide Description [Not Specified]
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who were between 0-20 years of age and whose heights were measured at baseline and at any of the follow-up visits.
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 269 272
Least Squares Mean (Standard Error)
Unit of Measure: z-score/year
0.046  (0.013) 0.019  (0.013)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atenolol, Losartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.13
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
13.Secondary Outcome
Title Annual Rate of Change in Body Mass Index
Hide Description [Not Specified]
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants whose body mass indexes were measured at baseline and at any of the follow-up visits.
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 283 295
Least Squares Mean (Standard Error)
Unit of Measure: kg/m^2 per year
0.063  (0.044) 0.076  (0.044)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atenolol, Losartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.82
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
14.Secondary Outcome
Title Annual Rate of Change in Body Mass Index for Age Z-score
Hide Description [Not Specified]
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who were between 0-20 years of age and whose body mass index for age z-scores were measured at baseline and at any of the follow-up visits.
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 250 263
Least Squares Mean (Standard Error)
Unit of Measure: z-score/year
0.007  (0.022) 0.021  (0.022)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atenolol, Losartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.64
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
15.Secondary Outcome
Title Annual Rate of Change in Arm Span to Height Ratio
Hide Description [Not Specified]
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants whose arm span to height ratios were measured at baseline and at any of the follow-up visits.
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 301 303
Least Squares Mean (Standard Error)
Unit of Measure: 1/year
0.001  (0.001) 0.001  (0.001)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atenolol, Losartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.49
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
16.Secondary Outcome
Title Annual Rate of Change in Upper to Lower Segment Ratio
Hide Description [Not Specified]
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants whose upper to lower segment ratios were measured at baseline and at any of the follow-up visits.
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 301 301
Least Squares Mean (Standard Error)
Unit of Measure: 1/year
-0.014  (0.002) -0.015  (0.002)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atenolol, Losartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.59
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
17.Secondary Outcome
Title Number of Participants With Aortic Dissection.
Hide Description [Not Specified]
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received the treatment
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 303 305
Measure Type: Number
Unit of Measure: participants
0 2
18.Secondary Outcome
Title Event Rate of Aortic Dissection.
Hide Description Percentage of participants who had aortic dissection over a 3-year period following randomization.
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received the treatment
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 303 305
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
0
(0 to 0)
0.7
(0.2 to 2.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atenolol, Losartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.16
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
19.Secondary Outcome
Title Number of Participants With Aortic-root Surgery.
Hide Description [Not Specified]
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received the treatment
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 303 305
Measure Type: Number
Unit of Measure: participants
10 18
20.Secondary Outcome
Title Event Rate of Aortic-Root Surgery
Hide Description Percentage of participants who had aortic-root surgery over a 3-year period following randomization.
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received the treatment
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 303 305
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
3.4
(1.9 to 6.3)
6.0
(3.8 to 9.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atenolol, Losartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.13
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
21.Secondary Outcome
Title Number of Death.
Hide Description [Not Specified]
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received the treatment
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 303 305
Measure Type: Number
Unit of Measure: participants
0 1
22.Secondary Outcome
Title Event Rate of Death
Hide Description Percentage of participants who died over a 3-year period following randomization.
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received the treatment
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 303 305
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
0
(0 to 0)
0.3
(0 to 2.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atenolol, Losartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.32
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
23.Secondary Outcome
Title Number of Participants With the Composite Adverse Clinical Outcomes, Including Aortic Dissection, Aortic-root Surgery and Death.
Hide Description [Not Specified]
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received the treatment
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 303 305
Measure Type: Number
Unit of Measure: participants
10 19
24.Secondary Outcome
Title Event Rate of the Composite Adverse Clinical Outcomes, Including Aortic Dissection, Aortic-root Surgery and Death.
Hide Description Percentage of participants who had aortic dissection, aortic-root surgery or death over a 3-year period following randomization
Time Frame Up to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received the treatment
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 303 305
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
3.4
(1.9 to 6.3)
6.4
(4.1 to 9.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atenolol, Losartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.10
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
25.Secondary Outcome
Title Adverse Drug Reactions Reported at the Baseline Visit
Hide Description [Not Specified]
Time Frame At baseline
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 303 305
Measure Type: Number
Unit of Measure: participants
Headache, any severity 112 114
Headache, bothersome 10 10
Fatigue, any severity 84 105
Fatigue, bothersome 0 0
Mood alterations, any severity 54 49
Mood alterations, bothersome 7 3
Behavior changes, any severity 21 23
Behavior changes, bothersome 2 1
Insomnia, any severity 60 61
Insomnia, bothersome 2 2
Nightmares, any severity 52 53
Nightmares, bothersome 2 3
Dizziness with standing, any severity 60 58
Dizziness with standing, bothersome 0 2
Dizziness - other, any severity 25 27
Dizziness - other, bothersome 0 1
Fainting with loss of consciousness, any severity 5 9
Fainting with loss of consciousness, bothersome 5 9
Palpitations, any severity 60 53
Palpitations, bothersome 0 0
Chest pain, any severity 54 58
Chest pain, bothersome 1 5
Dyspnea, any severity 43 38
Dyspnea, bothersome 3 0
Wheezing, any severity 15 14
Wheezing, bothersome 2 1
Upper respiratory/Nasal congestion, any severity 106 117
Upper respiratory/Nasal congestion, bothersome 0 2
Cough, any severity 47 59
Cough, bothersome 1 0
Dysgeusia, any severity 10 3
Dysgeusia, bothersome 0 0
Stomach pain/Indigestion, any severity 47 61
Stomach pain/Indigestion, bothersome 0 1
Nausea, any severity 30 35
Nausea, bothersome 1 0
Vomiting, any severity 23 23
Vomiting, bothersome 0 0
Diarrhea, any severity 35 43
Diarrhea, bothersome 1 1
Constipation, any severity 44 35
Constipation, bothersome 0 0
Vascular (hands, feet), any severity 35 34
Vascular (hands, feet), bothersome 0 1
Muscle pain or Cramps, any severity 59 58
Muscle pain or Cramps, bothersome 2 4
Back pain, any severity 60 67
Back pain, bothersome 3 2
Periorbital edema, any severity 13 15
Periorbital edema, bothersome 0 0
Pedal edema, any severity 2 3
Pedal edema, bothersome 0 0
Other, any severity 21 16
Other, bothersome 3 1
26.Secondary Outcome
Title Adverse Drug Reactions Reported During Routine Follow-up Surveillance
Hide Description [Not Specified]
Time Frame From 6 months to 3 years following randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who had any of the follow-up visits after 6 months post-randomization.
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description:
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate.
Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
Overall Number of Participants Analyzed 291 297
Measure Type: Number
Unit of Measure: participants
Headache, any severity 202 208
Headache, bothersome 27 20
Fatigue, any severity 152 153
Fatigue, bothersome 7 5
Mood alterations, any severity 89 86
Mood alterations, bothersome 13 13
Behavior changes, any severity 51 46
Behavior changes, bothersome 5 8
Insomnia, any severity 108 107
Insomnia, bothersome 6 4
Nightmares, any severity 100 94
Nightmares, bothersome 7 4
Dizziness with standing, any severity 119 105
Dizziness with standing, bothersome 6 0
Dizziness - other, any severity 60 61
Dizziness - other, bothersome 2 0
Fainting with loss of consciousness, any severity 21 16
Fainting with loss of consciousness, bothersome 21 16
Palpitations, any severity 86 101
Palpitations, bothersome 0 0
Chest pain, any severity 114 106
Chest pain, bothersome 14 1
Dyspnea, any severity 75 72
Dyspnea, bothersome 1 3
Wheezing, any severity 36 32
Wheezing, bothersome 2 5
Upper respiratory/Nasal congestion, any severity 188 186
Upper respiratory/Nasal congestion, bothersome 3 3
Cough, any severity 117 113
Cough, bothersome 1 1
Dysgeusia, any severity 29 16
Dysgeusia, bothersome 0 0
Stomach pain/Indigestion, any severity 119 121
Stomach pain/Indigestion, bothersome 2 8
Nausea, any severity 99 78
Nausea, bothersome 0 0
Vomiting, any severity 81 75
Vomiting, bothersome 1 2
Diarrhea, any severity 94 90
Diarrhea, bothersome 1 3
Constipation, any severity 77 66
Constipation, bothersome 1 0
Vascular (hands, feet), any severity 73 66
Vascular (hands, feet), bothersome 0 0
Muscle pain or Cramps, any severity 148 124
Muscle pain or Cramps, bothersome 6 7
Back pain, any severity 137 134
Back pain, bothersome 5 8
Periorbital edema, any severity 22 27
Periorbital edema, bothersome 0 1
Pedal edema, any severity 6 5
Pedal edema, bothersome 0 0
Other, any severity 105 108
Other, bothersome 10 12
Time Frame The adverse event (AE) data were collected since randomization till the end of the study, for up to 3 years.
Adverse Event Reporting Description Serious AEs and important medical events (including pregnancy) were reported within 24 hours of first knowledge of event; Non-Serious AEs were reported within 7 calendar days of first knowledge of event.
 
Arm/Group Title Atenolol Losartan
Hide Arm/Group Description Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.5 - 4.0 mg/kg/day Atenolol (not to exceed a total dose of 250 mg), with a goal of a 20% or greater decrease in the mean heart rate. Participants with Marfan’s syndrome and ≥3 maximum aortic root z-score received 0.4 - 1.4 mg/kg/day Losartan (not to exceed a total dose of 100 mg).
All-Cause Mortality
Atenolol Losartan
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Atenolol Losartan
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   27/303 (8.91%)      33/305 (10.82%)    
Blood and lymphatic system disorders     
Blood/bone marrow(sickle cell crisis) *  0/303 (0.00%)  0 1/305 (0.33%)  1
Cardiac disorders     
Atrial fibrillation * 1  0/303 (0.00%)  0 2/305 (0.66%)  4
Left ventricular failure * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Pericarditis NOS * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Supraventricular tachycardia * 1  1/303 (0.33%)  1 1/305 (0.33%)  1
Valvular heart disease NOS * 1  0/303 (0.00%)  0 3/305 (0.98%)  3
Ventricular tachycardia * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Eye disorders     
Retinal detachment * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Gastrointestinal disorders     
Abdominal pain NOS * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Diarrhoea NOS * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Pancreatitis NOS * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
General disorders     
Chest pain * 1  1/303 (0.33%)  1 2/305 (0.66%)  2
Pyrexia * 1  1/303 (0.33%)  1 1/305 (0.33%)  1
Immune system disorders     
Autoimmune disorder NOS * 1  1/303 (0.33%)  2 1/305 (0.33%)  1
Hypersensitivity NOS * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Serum sickness * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Infections and infestations     
Cellulitis *  1/303 (0.33%)  1 0/305 (0.00%)  0
Pneumonia * 1  4/303 (1.32%)  5 1/305 (0.33%)  1
Respiratory tract infection NOS * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Soft tissue infection NOS * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Urinary tract infection NOS * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Viral infection *  0/303 (0.00%)  0 1/305 (0.33%)  1
Wound - snake bite *  0/303 (0.00%)  0 1/305 (0.33%)  1
Wound infection * 1  0/303 (0.00%)  0 1/305 (0.33%)  2
Injury, poisoning and procedural complications     
Haematoma * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Vascular: vessel injury-artery, other NOS *  0/303 (0.00%)  0 1/305 (0.33%)  1
Investigations     
Weight decreased * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Metabolism and nutrition disorders     
Dehydration * 1  3/303 (0.99%)  3 0/305 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Scoliosis * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Nervous system disorders     
Cerebral abscess *  1/303 (0.33%)  2 0/305 (0.00%)  0
Convulsions NOS * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Dizziness * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Headache * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Pregnancy, puerperium and perinatal conditions     
Pregnancy *  1/303 (0.33%)  1 2/305 (0.66%)  2
Psychiatric disorders     
Agitation * 1  1/303 (0.33%)  1 2/305 (0.66%)  3
Anxiety * 1  2/303 (0.66%)  2 0/305 (0.00%)  0
Depression * 1  3/303 (0.99%)  3 1/305 (0.33%)  1
Psychosis aggravated * 1  1/303 (0.33%)  1 1/305 (0.33%)  1
Renal and urinary disorders     
Urethral obstruction * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Reproductive system and breast disorders     
Uterine haemorrhage * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Respiratory, thoracic and mediastinal disorders     
Bronchospasm * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Epistaxis *  1/303 (0.33%)  1 0/305 (0.00%)  0
Pleural effusion * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Pneumonitis NOS * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Pneumothorax NOS * 1  3/303 (0.99%)  3 5/305 (1.64%)  7
Pulmonary/upper respiratory-other *  0/303 (0.00%)  0 1/305 (0.33%)  1
Skin and subcutaneous tissue disorders     
Culture wound negative * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Surgical and medical procedures     
Aortic root enlargement *  1/303 (0.33%)  1 0/305 (0.00%)  0
Cardiac General-other: mitral valve replacement *  1/303 (0.33%)  1 0/305 (0.00%)  0
Vascular disorders     
Thrombosis * 1  1/303 (0.33%)  1 1/305 (0.33%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE 3.0 MedDRA 6.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Atenolol Losartan
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   135/303 (44.55%)      121/305 (39.67%)    
Blood and lymphatic system disorders     
Anemia *  0/303 (0.00%)  0 1/305 (0.33%)  1
Haemoglobin * 1  0/303 (0.00%)  0 2/305 (0.66%)  2
Lymph node pain * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Cardiac disorders     
Cardiac General - Other - Murmur *  0/303 (0.00%)  0 1/305 (0.33%)  1
Cardiac General - other - nonresponsive and pale *  1/303 (0.33%)  1 0/305 (0.00%)  0
Palpitations * 1  9/303 (2.97%)  9 10/305 (3.28%)  10
Sinus tachycardia * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Supraventricular tachycardia * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Ear and labyrinth disorders     
Auditory/ear-other *  0/303 (0.00%)  0 1/305 (0.33%)  1
Hypersensitivity to sound *  0/303 (0.00%)  0 1/305 (0.33%)  1
Endocrine disorders     
Hot flushes NOS * 1  1/303 (0.33%)  1 1/305 (0.33%)  1
Eye disorders     
Conjunctivitis * 1  3/303 (0.99%)  3 1/305 (0.33%)  1
Eyelid function disorder NOS * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Lacrimation increased * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Ocular-other (L eye burning/redness 4 mos. s/p lensectomy with lens insertion) *  1/303 (0.33%)  1 0/305 (0.00%)  0
Ocular-other (right eye hemorrhage) *  1/303 (0.33%)  1 0/305 (0.00%)  0
Ocular/Visual - Squinting of OS to see things more clearly. *  1/303 (0.33%)  1 0/305 (0.00%)  0
Ocular/visual-other (redness and itching of eyes) *  0/303 (0.00%)  0 1/305 (0.33%)  1
Photopsia * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Vision blurred * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain NOS * 1  7/303 (2.31%)  7 7/305 (2.30%)  7
Constipation * 1  4/303 (1.32%)  4 2/305 (0.66%)  2
Diarrhoea NOS * 1  4/303 (1.32%)  6 2/305 (0.66%)  2
Dysgeusia * 1  3/303 (0.99%)  3 2/305 (0.66%)  2
Dyspepsia * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Dysphagia * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Gastrointestinal - HERNIA *  0/303 (0.00%)  0 1/305 (0.33%)  1
Haemorrhoids * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Intestinal Hernia *  1/303 (0.33%)  1 0/305 (0.00%)  0
Nausea * 1  2/303 (0.66%)  2 2/305 (0.66%)  3
Oesophageal pain * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Oral pain * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Oseophagitis NOS * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Peridontal disorder NOS * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Stomach discomfort * 1  5/303 (1.65%)  5 3/305 (0.98%)  3
Tooth disorder NOS * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Vomiting NOS * 1  2/303 (0.66%)  3 5/305 (1.64%)  7
General disorders     
Bilateral pedal edema *  0/303 (0.00%)  0 1/305 (0.33%)  1
Chest pain * 1  16/303 (5.28%)  18 17/305 (5.57%)  18
Constitutional symptoms -other(flu) *  1/303 (0.33%)  1 0/305 (0.00%)  0
Constitutional symptoms-other (unusual dreams) *  1/303 (0.33%)  1 0/305 (0.00%)  0
Constitutional-other (general body cold sensation) *  0/303 (0.00%)  0 1/305 (0.33%)  1
Edema:head and neck *  2/303 (0.66%)  2 2/305 (0.66%)  2
Edema:limb *  1/303 (0.33%)  1 1/305 (0.33%)  2
Falling asleep *  1/303 (0.33%)  1 0/305 (0.00%)  0
Fatigue * 1  18/303 (5.94%)  19 11/305 (3.61%)  12
Hypothermia * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Influenza-like illness * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Nightmare *  7/303 (2.31%)  8 13/305 (4.26%)  13
Pain-other (right hip pain) *  1/303 (0.33%)  1 0/305 (0.00%)  0
Pain-other:chest pain/costochondritis (diagnosed in ER as costochondritis) *  1/303 (0.33%)  1 0/305 (0.00%)  0
Pyrexia * 1  4/303 (1.32%)  6 2/305 (0.66%)  2
Immune system disorders     
Allergy/Immunology - Other (rash) *  0/303 (0.00%)  0 1/305 (0.33%)  1
Hypersensitivity NOS * 1  0/303 (0.00%)  0 3/305 (0.98%)  3
Infections and infestations     
Abcessed tooth *  1/303 (0.33%)  1 0/305 (0.00%)  0
Bronchitis NOS * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Gum infection *  0/303 (0.00%)  0 1/305 (0.33%)  1
Infection - Eye NOS *  1/303 (0.33%)  1 0/305 (0.00%)  0
Infection - Other - Parvovirus *  0/303 (0.00%)  0 1/305 (0.33%)  1
Infection Pharnyx *  1/303 (0.33%)  1 1/305 (0.33%)  1
Infection with unknown ANC-eye, NOS *  0/303 (0.00%)  0 1/305 (0.33%)  1
Infection with unknown ANC-middle ear *  0/303 (0.00%)  0 1/305 (0.33%)  1
Infection with unknown ANC-pharynx *  0/303 (0.00%)  0 2/305 (0.66%)  2
Infection with unknown ANC-sinus *  0/303 (0.00%)  0 1/305 (0.33%)  1
Infection with unknown ANC-upper ariway NOS *  2/303 (0.66%)  2 0/305 (0.00%)  0
Infection-bladder(urinary) *  0/303 (0.00%)  0 1/305 (0.33%)  1
Infection-other (sinus, bronchitis, pharyngeal) *  1/303 (0.33%)  1 0/305 (0.00%)  0
Infection-other (skin on foot) *  0/303 (0.00%)  0 1/305 (0.33%)  1
Infection-other-Lyme disease *  0/303 (0.00%)  0 1/305 (0.33%)  1
Infection: Dental - Tooth *  1/303 (0.33%)  1 0/305 (0.00%)  0
Middle ear infection *  1/303 (0.33%)  1 2/305 (0.66%)  2
Mononucleosis *  3/303 (0.99%)  3 1/305 (0.33%)  1
Pneumonia * 1  1/303 (0.33%)  1 4/305 (1.31%)  4
Shingles *  0/303 (0.00%)  0 1/305 (0.33%)  1
Sinus infection *  2/303 (0.66%)  2 0/305 (0.00%)  0
Sinusitis NOS * 1  2/303 (0.66%)  2 1/305 (0.33%)  1
Urinary tract infection NOS * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Vaginitis *  1/303 (0.33%)  1 0/305 (0.00%)  0
Viral infection coxsackievirus *  1/303 (0.33%)  1 0/305 (0.00%)  0
Injury, poisoning and procedural complications     
Haematoma * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Investigations     
Neutrophil count * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Weight decreased * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Metabolism and nutrition disorders     
Anorexia * 1  1/303 (0.33%)  1 3/305 (0.98%)  3
Dehydration * 1  1/303 (0.33%)  1 1/305 (0.33%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  3/303 (0.99%)  3 3/305 (0.98%)  3
Back pain * 1  8/303 (2.64%)  8 8/305 (2.62%)  8
Chest wall pain * 1  6/303 (1.98%)  6 5/305 (1.64%)  5
Joint disorder NOS * 1  1/303 (0.33%)  1 1/305 (0.33%)  1
Joint effusion * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Msk/soft tissue, other (Nodule on back) *  0/303 (0.00%)  0 1/305 (0.33%)  1
Muscle weakness, generalized or specific area *  1/303 (0.33%)  1 0/305 (0.00%)  0
Musculoskeletal (other) (loose joints-causing pain) *  1/303 (0.33%)  1 0/305 (0.00%)  0
Musculoskeletal/soft tissue - other (patellar dislocation) *  1/303 (0.33%)  1 0/305 (0.00%)  0
Musculoskeletal/soft tissue-other (Bursa on left shoulder blade due to back brace) *  0/303 (0.00%)  0 1/305 (0.33%)  1
Musculoskeletal/soft tissue-other (nodule on back) *  0/303 (0.00%)  0 1/305 (0.33%)  1
Musculoskeletal/soft tissue-other( left arm pain) *  0/303 (0.00%)  0 1/305 (0.33%)  1
Myalgia * 1  3/303 (0.99%)  3 12/305 (3.93%)  12
Neck pain * 1  1/303 (0.33%)  1 2/305 (0.66%)  2
Pain in extremity * 1  5/303 (1.65%)  5 4/305 (1.31%)  4
Nervous system disorders     
Cognitive disorder * 1  2/303 (0.66%)  2 2/305 (0.66%)  2
Convulsions NOS * 1  3/303 (0.99%)  3 0/305 (0.00%)  0
Dizziness * 1  29/303 (9.57%)  29 17/305 (5.57%)  18
Dizziness upon standing *  1/303 (0.33%)  1 1/305 (0.33%)  1
Extrapyramidal disorder * 1  2/303 (0.66%)  2 0/305 (0.00%)  0
Headache * 1  31/303 (10.23%)  36 18/305 (5.90%)  19
Memory impairment * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Mental status changes * 1  1/303 (0.33%)  1 1/305 (0.33%)  1
Neuralgia NOS * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Neurology - other *  0/303 (0.00%)  0 2/305 (0.66%)  2
Neurology-other (panic attacks) *  0/303 (0.00%)  0 1/305 (0.33%)  2
Panick attack *  1/303 (0.33%)  1 0/305 (0.00%)  0
Syncope * 1  13/303 (4.29%)  14 9/305 (2.95%)  9
Syncope vasovagal * 1  2/303 (0.66%)  2 2/305 (0.66%)  3
Tremor * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Pregnancy, puerperium and perinatal conditions     
Sexual/reproductive function-other (4.5 cm cyst on right ovary) *  0/303 (0.00%)  0 1/305 (0.33%)  1
Sexual/reproductive function-other (abnormal pap smear) *  0/303 (0.00%)  0 1/305 (0.33%)  1
Psychiatric disorders     
Agitation * 1  11/303 (3.63%)  12 3/305 (0.98%)  3
Anxiety * 1  5/303 (1.65%)  5 2/305 (0.66%)  2
Confusional state * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Depression * 1  9/303 (2.97%)  11 2/305 (0.66%)  3
Insomnia * 1  10/303 (3.30%)  10 12/305 (3.93%)  12
Mood alteration *  1/303 (0.33%)  1 0/305 (0.00%)  0
Neurology-other (expression of anger and sadness) *  1/303 (0.33%)  1 0/305 (0.00%)  0
Neurology-other (irritability) *  0/303 (0.00%)  0 1/305 (0.33%)  1
Personality change * 1  6/303 (1.98%)  6 3/305 (0.98%)  3
Renal and urinary disorders     
Chromaturia * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Pollakiuria * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Renal/genitourinary-increased urinary frequency, daytime only, associated w/ po water intake *  0/303 (0.00%)  0 1/305 (0.33%)  1
Urinary incontinence * 1  1/303 (0.33%)  2 0/305 (0.00%)  0
Urogenital haemorrhage * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Reproductive system and breast disorders     
Gynaecomastia * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Vaginal haemorrhage * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Respiratory, thoracic and mediastinal disorders     
Bronchospasm * 1  3/303 (0.99%)  3 4/305 (1.31%)  4
Cough * 1  3/303 (0.99%)  3 4/305 (1.31%)  4
Dyspnoea * 1  6/303 (1.98%)  6 5/305 (1.64%)  5
Epistaxis *  9/303 (2.97%)  9 7/305 (2.30%)  7
Hemorrhage/Bleeding - other *  1/303 (0.33%)  1 0/305 (0.00%)  0
Hypoxia * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Nasal congestion *  2/303 (0.66%)  2 3/305 (0.98%)  3
Nasal conjestion/inf with unk ANC upper airway NOS *  1/303 (0.33%)  1 0/305 (0.00%)  0
Obstructive sleep apnea *  0/303 (0.00%)  0 1/305 (0.33%)  1
Pulmonary/upper respiratory-other *  1/303 (0.33%)  1 0/305 (0.00%)  0
Upper Respiratory - Other *  0/303 (0.00%)  0 1/305 (0.33%)  1
Skin and subcutaneous tissue disorders     
Acne NOS * 1  2/303 (0.66%)  2 2/305 (0.66%)  2
Alopecia * 1  1/303 (0.33%)  1 4/305 (1.31%)  4
Burn on skin *  1/303 (0.33%)  1 0/305 (0.00%)  0
Decubitus ulcer * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Derm/skin-other (Poison Ivy) *  1/303 (0.33%)  1 0/305 (0.00%)  0
Derm/skin-other (mild chin rash) *  1/303 (0.33%)  1 0/305 (0.00%)  0
Derm/skin-other (possible aczema) *  1/303 (0.33%)  1 0/305 (0.00%)  0
Derm/skin-other (worsening of underlying hand skin disorder) *  0/303 (0.00%)  0 1/305 (0.33%)  1
Dermatitis exfoliative NOS * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Dermatology - other - Erythema Nodosum *  1/303 (0.33%)  1 0/305 (0.00%)  0
Dermatology/skin-other (Poison Ivy) *  1/303 (0.33%)  1 0/305 (0.00%)  0
Dermatology/skin-other (cervical dysplasia) *  1/303 (0.33%)  1 0/305 (0.00%)  0
Dermatology/skin-other (papules on legs) *  0/303 (0.00%)  0 1/305 (0.33%)  1
Dermatology/skin-other (rash: nonspecific maculopapular rash) *  0/303 (0.00%)  0 1/305 (0.33%)  1
Ecchymosis * 1  1/303 (0.33%)  1 2/305 (0.66%)  2
Eczema *  1/303 (0.33%)  1 1/305 (0.33%)  1
Erythema multiforme * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
Pruritus * 1  3/303 (0.99%)  4 0/305 (0.00%)  0
Rash *  1/303 (0.33%)  1 0/305 (0.00%)  0
Rash on torso and neck *  0/303 (0.00%)  0 1/305 (0.33%)  1
Skin irritation *  1/303 (0.33%)  1 2/305 (0.66%)  3
Sweating increased * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Urticaria NOS * 1  3/303 (0.99%)  3 4/305 (1.31%)  4
Surgical and medical procedures     
Cardiac general-chest tightness *  0/303 (0.00%)  0 1/305 (0.33%)  1
Vascular disorders     
Flushing * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Hypertension NOS * 1  1/303 (0.33%)  1 0/305 (0.00%)  0
Hypotension NOS * 1  0/303 (0.00%)  0 3/305 (0.98%)  3
Raynaud's Phenomena *  2/303 (0.66%)  2 1/305 (0.33%)  1
Thrombosis * 1  0/303 (0.00%)  0 1/305 (0.33%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE 3.0 MedDRA 6.0

The effect of losartan on TGF-β was not assessed. The study results do not apply to Marfan subjects whose BSA–adj. aortic-root z score is ≤3.

Subjects may find their treatment based on the appearance of the drug.

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.
All publications and presentations resulting from studies from the PHN Network must be approved by the Publications and Presentations Committee before submission. The Sponsor (NERI) and funding agency (NHLBI) both are represented on the P&P Committee along with Network Investigators. Members of the P&P Committee can recommend changes to publications.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Paul Stark, PhD
Organization: New England Research Institutes, Inc.
Phone: 617-972-3362
EMail: pstark@neriscience.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: New England Research Institutes
ClinicalTrials.gov Identifier: NCT00429364     History of Changes
Other Study ID Numbers: 461
U01HL068270 ( U.S. NIH Grant/Contract )
First Submitted: January 29, 2007
First Posted: January 31, 2007
Results First Submitted: February 25, 2015
Results First Posted: April 1, 2015
Last Update Posted: April 1, 2015