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CompletedNCT00429364Updated Mar 7, 2025Results posted

Comparison of Two Medications Aimed at Slowing Aortic Root Enlargement in Individuals With Marfan Syndrome

A Phase 3 interventional study of Losartan Potassium and Atenolol in Marfan Syndrome, sponsored by Carelon Research. Completed at 26 sites in 3 countries. Open to participants aged 6 Months to 25 Years. Per ClinicalTrials.gov, last updated 2025-03-07.

Sponsored by Carelon Research · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
608
Allocation
Randomized
Ages
6 Months to 25 Years
Sex
All
01

Study summary

Marfan syndrome is a hereditary connective tissue disorder. Many individuals with this condition die because of the associated heart and blood vessel abnormalities. This study will compare the effectiveness of two medications, losartan and atenolol, at slowing aortic root enlargement in individuals with Marfan syndrome.

Read the detailed description

Marfan syndrome is an inheritable disorder that affects the body's connective tissue. An abnormal protein results in connective tissue that is weaker than normal. Because connective tissue is found throughout the body, Marfan syndrome can affect many body systems, including the skeleton, eyes, nervous system, skin, lungs, heart, and blood vessels. Overall, heart and blood vessel abnormalities are the leading cause of death in individuals with Marfan syndrome. A common blood vessel abnormality associated with this disease involves the aorta, which is the large artery that carries blood away from the heart to the rest of the body. The aortic root, the portion of the aorta that is attached to the heart, may enlarge and tear or even rupture. A tear or rupture is considered a life-threatening emergency. Recent studies have shown that the medication losartan may reduce aortic root growth and improve heart function. The purpose of this study is to compare the effectiveness of losartan versus atenolol at slowing aortic root growth in individuals with Marfan syndrome.

This 3-year study will enroll individuals with Marfan syndrome. Participants will be randomly assigned to receive either losartan or atenolol on a daily basis. All participants will initially receive a low dose of their assigned medication. This dose will be gradually increased every 3 to 4 weeks until the maximum tolerated dose is reached. A continuous electrocardiogram (ECG) that monitors heart rate and activity in 24-hour intervals will be used to determine the proper dose increase for each participant. Participants will then receive the maximum tolerated dose for the remainder of the study. Study visits will occur at baseline and Months 6, 12, 24, and 36. Each study visit will include a physical examination, a medical history review, an ECG, an echocardiogram, and questionnaires. Additionally, at the baseline study visit blood will be collected for laboratory testing.

02

Conditions studied

  • Marfan Syndrome

Keywords

  • Aortic Root Dissection
  • Aortic Root Dilation
  • Pediatric Heart Network
03

In context

Marfan Syndrome

71 studies on the registry are indexed under Marfan Syndrome; 16 are open to participants now.

This study's enrollment of 608 is above the median of 40 across 31 interventional studies indexed under Marfan Syndrome.

Browse Marfan Syndrome studies →

Lead sponsor

Carelon Research is the lead sponsor of 55 studies on the registry; 4 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
6 Months to 25 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Diagnosis of Marfan syndrome, according to Ghent criteria (more information can be found in Appendix D of the protocol)
  • Aortic root Z-score greater than 3.0

Exclusion criteria

Exclusion Criteria:

  • Prior aortic surgery
  • Aortic root dimension at the sinuses of Valsalva greater than 5 cm
  • Planned aortic surgery within 6 months of study entry
  • Aortic dissection
  • Shprintzen-Goldberg syndrome
  • Loeys-Dietz syndrome
  • Therapeutic (i.e., for arrhythmia, ventricular dysfunction, or valve regurgitation) rather than prophylactic use of angiotensin-converting enzyme (ACE) inhibitor, beta-blocker, or calcium channel blocker
  • History of angioedema while taking an ACE inhibitor or beta-blocker
  • Intolerance to losartan or other angiotensin II receptor blocker (ARB) that resulted in termination of therapy
  • Intolerance to atenolol or other beta-blocker that resulted in termination of therapy
  • Kidney dysfunction (i.e., creatinine greater than the upper limit of age-related normal values)
  • Asthma of sufficient severity to prohibit the use of a beta-blocker
  • Chronic use of steroids and/or beta-adrenergic agents with exacerbations of asthma that are frequent (averaging three or more per year) or severe (requiring hospitalization)
  • Diabetes mellitus
  • Pregnant or planning to become pregnant within 36 months of study entry
  • Inability to complete study procedures, including history of poor acoustic windows (i.e., inability to obtain accurate measurement of aortic root)
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Outcomes assessor)
Enrollment
608 participants (actual)

Study arms

  • Active comparator
    Atenolol

    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.

    Drug: Atenolol

  • Active comparator
    Losartan

    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).

    Drug: Losartan Potassium

Interventions

  • DrugLosartan Potassium

    Losartan .3 - 1.4 mg/kg

    Also known as: Cozaar

  • DrugAtenolol

    Atenolol .5 - 4 mg/kg

    Also known as: Tenormin

06

What researchers measure

Primary outcomes

  1. Annual Rate of Change in Aortic Root (Sinuses of Valsalva) Body-surface-area-adjusted Z-score

    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.

Secondary outcomes

  1. Annual Rate of Change in Aortic Root (Sinuses of Valsalva) Absolute Dimension

    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.

  2. Annual Rate of Change in Ascending-aorta-diameter Z Score, Adjusted by Body-surface-area.

    Time frame: Up to 3 years following randomization.

  3. Annual Rate of Change in the Absolute Diameter of the Ascending Aorta

    Time frame: Up to 3 years following randomization.

  4. Annual Rate of Change in Aortic-annulus-diameter Z Score, Adjusted by Body-surface Area

    Time frame: Up to 3 years following randomization.

  5. Annual Rate of Change in the Absolute Diameter of the Aortic Annulus

    Time frame: Up to 3 years following randomization.

  6. Annual Rate of Change in Total Aortic Proximal Regurgitant Jet Area Indexed to Body-surface-area

    Time frame: Up to 3 years following randomization.

  7. Annual Rate of Change in Weight

    Time frame: Up to 3 years following randomization.

  8. Annual Rate of Change in Weight-for-age Z-score

    Time frame: Up to 3 years following randomization.

  9. Annual Rate of Change in Weight-for-height Z-score

    Time frame: Up to 3 years following randomization.

  10. Annual Rate of Change in Height

    Time frame: Up to 3 years following randomization.

  11. Annual Rate of Change in Height-for-age Z-score

    Time frame: Up to 3 years following randomization.

  12. Annual Rate of Change in Body Mass Index

    Time frame: Up to 3 years following randomization.

  13. Annual Rate of Change in Body Mass Index for Age Z-score

    Time frame: Up to 3 years following randomization.

  14. Annual Rate of Change in Arm Span to Height Ratio

    Time frame: Up to 3 years following randomization.

  15. Annual Rate of Change in Upper to Lower Segment Ratio

    Time frame: Up to 3 years following randomization.

  16. Number of Participants With Aortic Dissection.

    Time frame: Up to 3 years following randomization.

  17. Event Rate of Aortic Dissection.

    Percentage of participants who had aortic dissection over a 3-year period following randomization.

    Time frame: Up to 3 years following randomization.

  18. Number of Participants With Aortic-root Surgery.

    Time frame: Up to 3 years following randomization.

  19. Event Rate of Aortic-Root Surgery

    Percentage of participants who had aortic-root surgery over a 3-year period following randomization.

    Time frame: Up to 3 years following randomization.

  20. Number of Death.

    Time frame: Up to 3 years following randomization.

  21. Event Rate of Death

    Percentage of participants who died over a 3-year period following randomization.

    Time frame: Up to 3 years following randomization.

  22. Number of Participants With the Composite Adverse Clinical Outcomes, Including Aortic Dissection, Aortic-root Surgery and Death.

    Time frame: Up to 3 years following randomization.

  23. Event Rate of the Composite Adverse Clinical Outcomes, Including Aortic Dissection, Aortic-root Surgery and Death.

    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.

  24. Adverse Drug Reactions Reported at the Baseline Visit

    Time frame: At baseline

  25. Adverse Drug Reactions Reported During Routine Follow-up Surveillance

    Time frame: From 6 months to 3 years following randomization.

07

Results

Posted Apr 1, 2015
Limitations and caveats
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.

Participant flow

From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants into the study.

Participant flow — Overall Study
MilestoneAtenololLosartan
Started303305
Completed271272
Not completed3233
Withdrew: Withdrawal by subject115
Withdrew: Physician decision42
Withdrew: Lost to follow-up76
Withdrew: Death01
Withdrew: Underwent aortic root surgery1018
Withdrew: Pregnancy01

Outcome measures

PrimaryAnnual Rate of Change in Aortic Root (Sinuses of Valsalva) Body-surface-area-adjusted Z-score

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.
Reported as:
Least squares mean · z-score/year
Annual Rate of Change in Aortic Root (Sinuses of Valsalva) Body-surface-area-adjusted Z-score
z-score/yearAtenololLosartan
Annual Rate of Change in Aortic Root (Sinuses of Valsalva) Body-surface-area-adjusted Z-score-0.139 ± 0.013-0.107 ± 0.013
Statistical analysis
  • Atenolol vs Losartan · Mixed Models Analysis · p = 0.08 (P values are based on a linear regression mixed-effect model comparing slopes under compound symmetry, with adjustment for baseline.)
SecondaryAnnual Rate of Change in Aortic Root (Sinuses of Valsalva) Absolute Dimension

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.
Reported as:
Least squares mean · cm/year
Annual Rate of Change in Aortic Root (Sinuses of Valsalva) Absolute Dimension
cm/yearAtenololLosartan
Annual Rate of Change in Aortic Root (Sinuses of Valsalva) Absolute Dimension0.069 ± 0.0040.075 ± 0.004
Statistical analysis
  • Atenolol vs Losartan · Mixed Models Analysis · p = 0.20 (P values are based on a linear regression mixed-effect model comparing slopes under compound symmetry, with adjustment for baseline.)
SecondaryAnnual Rate of Change in Ascending-aorta-diameter Z Score, Adjusted by Body-surface-area.
Time frame:
Up to 3 years following randomization.
Reported as:
Least squares mean · z-score/year
Annual Rate of Change in Ascending-aorta-diameter Z Score, Adjusted by Body-surface-area.
z-score/yearAtenololLosartan
Annual Rate of Change in Ascending-aorta-diameter Z Score, Adjusted by Body-surface-area.-0.140 ± 0.013-0.114 ± 0.013
Statistical analysis
  • Atenolol vs Losartan · Mixed Models Analysis · p = 0.15 (P values are based on a linear regression mixed-effect model comparing slopes under compound symmetry, with adjustment for baseline.)
SecondaryAnnual Rate of Change in the Absolute Diameter of the Ascending Aorta
Time frame:
Up to 3 years following randomization.
Reported as:
Least squares mean · cm/year
Annual Rate of Change in the Absolute Diameter of the Ascending Aorta
cm/yearAtenololLosartan
Annual Rate of Change in the Absolute Diameter of the Ascending Aorta0.039 ± 0.0040.044 ± 0.004
Statistical analysis
  • Atenolol vs Losartan · Mixed Models Analysis · p = 0.30 (P values are based on a linear regression mixed-effect model comparing slopes under compound symmetry, with adjustment for baseline.)
SecondaryAnnual Rate of Change in Aortic-annulus-diameter Z Score, Adjusted by Body-surface Area
Time frame:
Up to 3 years following randomization.
Reported as:
Least squares mean · z-score/year
Annual Rate of Change in Aortic-annulus-diameter Z Score, Adjusted by Body-surface Area
z-score/yearAtenololLosartan
Annual Rate of Change in Aortic-annulus-diameter Z Score, Adjusted by Body-surface Area-0.279 ± 0.018-0.175 ± 0.018
Statistical analysis
  • Atenolol vs Losartan · Mixed Models Analysis · p = <0.001 (P values are based on a linear regression mixed-effect model comparing slopes under compound symmetry, with adjustment for baseline.)
SecondaryAnnual Rate of Change in the Absolute Diameter of the Aortic Annulus
Time frame:
Up to 3 years following randomization.
Reported as:
Least squares mean · cm/year
Annual Rate of Change in the Absolute Diameter of the Aortic Annulus
cm/yearAtenololLosartan
Annual Rate of Change in the Absolute Diameter of the Aortic Annulus0.015 ± 0.0030.030 ± 0.003
Statistical analysis
  • Atenolol vs Losartan · Mixed Models Analysis · p = 0.002 (P values are based on a linear regression mixed-effect model comparing slopes under compound symmetry, with adjustment for baseline.)
SecondaryAnnual Rate of Change in Total Aortic Proximal Regurgitant Jet Area Indexed to Body-surface-area
Time frame:
Up to 3 years following randomization.
Reported as:
Least squares mean · (mm^2/m^2)/year
Annual Rate of Change in Total Aortic Proximal Regurgitant Jet Area Indexed to Body-surface-area
(mm^2/m^2)/yearAtenololLosartan
Annual Rate of Change in Total Aortic Proximal Regurgitant Jet Area Indexed to Body-surface-area0.005 ± 0.0030.001 ± 0.003
Statistical analysis
  • Atenolol vs Losartan · Mixed Models Analysis · p = 0.29 (P values are based on a linear regression mixed-effect model comparing slopes under compound symmetry, with adjustment for baseline.)
SecondaryAnnual Rate of Change in Weight
Time frame:
Up to 3 years following randomization.
Reported as:
Least squares mean · kg/year
Annual Rate of Change in Weight
kg/yearAtenololLosartan
Annual Rate of Change in Weight0.239 ± 0.1530.229 ± 0.154
Statistical analysis
  • Atenolol vs Losartan · Mixed Models Analysis · p = 0.96 (Regression model adjusted for age at study visit.)
SecondaryAnnual Rate of Change in Weight-for-age Z-score
Time frame:
Up to 3 years following randomization.
Reported as:
Least squares mean · z-score/year
Annual Rate of Change in Weight-for-age Z-score
z-score/yearAtenololLosartan
Annual Rate of Change in Weight-for-age Z-score0.011 ± 0.0130.019 ± 0.013
Statistical analysis
  • Atenolol vs Losartan · Mixed Models Analysis · p = 0.45
SecondaryAnnual Rate of Change in Weight-for-height Z-score
Time frame:
Up to 3 years following randomization.
Reported as:
Least squares mean · z-score/year
Annual Rate of Change in Weight-for-height Z-score
z-score/yearAtenololLosartan
Annual Rate of Change in Weight-for-height Z-score-0.001 ± 0.072-0.157 ± 0.076
Statistical analysis
  • Atenolol vs Losartan · Mixed Models Analysis · p = 0.13
SecondaryAnnual Rate of Change in Height
Time frame:
Up to 3 years following randomization.
Reported as:
Least squares mean · cm/year
Annual Rate of Change in Height
cm/yearAtenololLosartan
Annual Rate of Change in Height0.822 ± 0.2040.935 ± 0.202
Statistical analysis
  • Atenolol vs Losartan · Mixed Models Analysis · p = 0.65
SecondaryAnnual Rate of Change in Height-for-age Z-score
Time frame:
Up to 3 years following randomization.
Reported as:
Least squares mean · z-score/year
Annual Rate of Change in Height-for-age Z-score
z-score/yearAtenololLosartan
Annual Rate of Change in Height-for-age Z-score0.046 ± 0.0130.019 ± 0.013
Statistical analysis
  • Atenolol vs Losartan · Mixed Models Analysis · p = 0.13
SecondaryAnnual Rate of Change in Body Mass Index
Time frame:
Up to 3 years following randomization.
Reported as:
Least squares mean · kg/m^2 per year
Annual Rate of Change in Body Mass Index
kg/m^2 per yearAtenololLosartan
Annual Rate of Change in Body Mass Index0.063 ± 0.0440.076 ± 0.044
Statistical analysis
  • Atenolol vs Losartan · Mixed Models Analysis · p = 0.82
SecondaryAnnual Rate of Change in Body Mass Index for Age Z-score
Time frame:
Up to 3 years following randomization.
Reported as:
Least squares mean · z-score/year
Annual Rate of Change in Body Mass Index for Age Z-score
z-score/yearAtenololLosartan
Annual Rate of Change in Body Mass Index for Age Z-score0.007 ± 0.0220.021 ± 0.022
Statistical analysis
  • Atenolol vs Losartan · Mixed Models Analysis · p = 0.64
SecondaryAnnual Rate of Change in Arm Span to Height Ratio
Time frame:
Up to 3 years following randomization.
Reported as:
Least squares mean · 1/year
Annual Rate of Change in Arm Span to Height Ratio
1/yearAtenololLosartan
Annual Rate of Change in Arm Span to Height Ratio0.001 ± 0.0010.001 ± 0.001
Statistical analysis
  • Atenolol vs Losartan · Mixed Models Analysis · p = 0.49
SecondaryAnnual Rate of Change in Upper to Lower Segment Ratio
Time frame:
Up to 3 years following randomization.
Reported as:
Least squares mean · 1/year
Annual Rate of Change in Upper to Lower Segment Ratio
1/yearAtenololLosartan
Annual Rate of Change in Upper to Lower Segment Ratio-0.014 ± 0.002-0.015 ± 0.002
Statistical analysis
  • Atenolol vs Losartan · Mixed Models Analysis · p = 0.59
SecondaryNumber of Participants With Aortic Dissection.
Time frame:
Up to 3 years following randomization.
Reported as:
Number · participants
Number of Participants With Aortic Dissection.
participantsAtenololLosartan
Number of Participants With Aortic Dissection.02
SecondaryEvent Rate of Aortic Dissection.

Percentage of participants who had aortic dissection over a 3-year period following randomization.

Time frame:
Up to 3 years following randomization.
Reported as:
Number · Percentage of participants
Event Rate of Aortic Dissection.
Percentage of participantsAtenololLosartan
Event Rate of Aortic Dissection.0 (0 to 0)0.7 (0.2 to 2.7)
Statistical analysis
  • Atenolol vs Losartan · Log Rank · p = 0.16
SecondaryNumber of Participants With Aortic-root Surgery.
Time frame:
Up to 3 years following randomization.
Reported as:
Number · participants
Number of Participants With Aortic-root Surgery.
participantsAtenololLosartan
Number of Participants With Aortic-root Surgery.1018
SecondaryEvent Rate of Aortic-Root Surgery

Percentage of participants who had aortic-root surgery over a 3-year period following randomization.

Time frame:
Up to 3 years following randomization.
Reported as:
Number · Percentage of participants
Event Rate of Aortic-Root Surgery
Percentage of participantsAtenololLosartan
Event Rate of Aortic-Root Surgery3.4 (1.9 to 6.3)6.0 (3.8 to 9.4)
Statistical analysis
  • Atenolol vs Losartan · Log Rank · p = 0.13
SecondaryNumber of Death.
Time frame:
Up to 3 years following randomization.
Reported as:
Number · participants
Number of Death.
participantsAtenololLosartan
Number of Death.01
SecondaryEvent Rate of Death

Percentage of participants who died over a 3-year period following randomization.

Time frame:
Up to 3 years following randomization.
Reported as:
Number · Percentage of participants
Event Rate of Death
Percentage of participantsAtenololLosartan
Event Rate of Death0 (0 to 0)0.3 (0 to 2.4)
Statistical analysis
  • Atenolol vs Losartan · Log Rank · p = 0.32
SecondaryNumber of Participants With the Composite Adverse Clinical Outcomes, Including Aortic Dissection, Aortic-root Surgery and Death.
Time frame:
Up to 3 years following randomization.
Reported as:
Number · participants
Number of Participants With the Composite Adverse Clinical Outcomes, Including Aortic Dissection, Aortic-root Surgery and Death.
participantsAtenololLosartan
Number of Participants With the Composite Adverse Clinical Outcomes, Including Aortic Dissection, Aortic-root Surgery and Death.1019
SecondaryEvent Rate of the Composite Adverse Clinical Outcomes, Including Aortic Dissection, Aortic-root Surgery and Death.

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.
Reported as:
Number · Percentage of participants
Event Rate of the Composite Adverse Clinical Outcomes, Including Aortic Dissection, Aortic-root Surgery and Death.
Percentage of participantsAtenololLosartan
Event Rate of the Composite Adverse Clinical Outcomes, Including Aortic Dissection, Aortic-root Surgery and Death.3.4 (1.9 to 6.3)6.4 (4.1 to 9.8)
Statistical analysis
  • Atenolol vs Losartan · Log Rank · p = 0.10
SecondaryAdverse Drug Reactions Reported at the Baseline Visit
Time frame:
At baseline
Reported as:
Number · participants
Adverse Drug Reactions Reported at the Baseline Visit
participantsAtenololLosartan
Headache, any severity112114
Headache, bothersome1010
Fatigue, any severity84105
Fatigue, bothersome00
Mood alterations, any severity5449
Mood alterations, bothersome73
Behavior changes, any severity2123
Behavior changes, bothersome21
Insomnia, any severity6061
Insomnia, bothersome22
Nightmares, any severity5253
Nightmares, bothersome23
Dizziness with standing, any severity6058
Dizziness with standing, bothersome02
Dizziness - other, any severity2527
Dizziness - other, bothersome01
Fainting with loss of consciousness, any severity59
Fainting with loss of consciousness, bothersome59
Palpitations, any severity6053
Palpitations, bothersome00
Chest pain, any severity5458
Chest pain, bothersome15
Dyspnea, any severity4338
Dyspnea, bothersome30
Wheezing, any severity1514
Wheezing, bothersome21
Upper respiratory/Nasal congestion, any severity106117
Upper respiratory/Nasal congestion, bothersome02
Cough, any severity4759
Cough, bothersome10
Dysgeusia, any severity103
Dysgeusia, bothersome00
Stomach pain/Indigestion, any severity4761
Stomach pain/Indigestion, bothersome01
Nausea, any severity3035
Nausea, bothersome10
Vomiting, any severity2323
Vomiting, bothersome00
Diarrhea, any severity3543
Diarrhea, bothersome11
Constipation, any severity4435
Constipation, bothersome00
Vascular (hands, feet), any severity3534
Vascular (hands, feet), bothersome01
Muscle pain or Cramps, any severity5958
Muscle pain or Cramps, bothersome24
Back pain, any severity6067
Back pain, bothersome32
Periorbital edema, any severity1315
Periorbital edema, bothersome00
Pedal edema, any severity23
Pedal edema, bothersome00
Other, any severity2116
Other, bothersome31
SecondaryAdverse Drug Reactions Reported During Routine Follow-up Surveillance
Time frame:
From 6 months to 3 years following randomization.
Reported as:
Number · participants
Adverse Drug Reactions Reported During Routine Follow-up Surveillance
participantsAtenololLosartan
Headache, any severity202208
Headache, bothersome2720
Fatigue, any severity152153
Fatigue, bothersome75
Mood alterations, any severity8986
Mood alterations, bothersome1313
Behavior changes, any severity5146
Behavior changes, bothersome58
Insomnia, any severity108107
Insomnia, bothersome64
Nightmares, any severity10094
Nightmares, bothersome74
Dizziness with standing, any severity119105
Dizziness with standing, bothersome60
Dizziness - other, any severity6061
Dizziness - other, bothersome20
Fainting with loss of consciousness, any severity2116
Fainting with loss of consciousness, bothersome2116
Palpitations, any severity86101
Palpitations, bothersome00
Chest pain, any severity114106
Chest pain, bothersome141
Dyspnea, any severity7572
Dyspnea, bothersome13
Wheezing, any severity3632
Wheezing, bothersome25
Upper respiratory/Nasal congestion, any severity188186
Upper respiratory/Nasal congestion, bothersome33
Cough, any severity117113
Cough, bothersome11
Dysgeusia, any severity2916
Dysgeusia, bothersome00
Stomach pain/Indigestion, any severity119121
Stomach pain/Indigestion, bothersome28
Nausea, any severity9978
Nausea, bothersome00
Vomiting, any severity8175
Vomiting, bothersome12
Diarrhea, any severity9490
Diarrhea, bothersome13
Constipation, any severity7766
Constipation, bothersome10
Vascular (hands, feet), any severity7366
Vascular (hands, feet), bothersome00
Muscle pain or Cramps, any severity148124
Muscle pain or Cramps, bothersome67
Back pain, any severity137134
Back pain, bothersome58
Periorbital edema, any severity2227
Periorbital edema, bothersome01
Pedal edema, any severity65
Pedal edema, bothersome00
Other, any severity105108
Other, bothersome1012

Adverse events

Collected over The adverse event (AE) data were collected since randomization till the end of the study, for up to 3 years.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Atenolol—27/303 (8.9%)135/303 (44.6%)
Losartan—33/305 (10.8%)121/305 (39.7%)
Most frequent serious events
Showing 10 of 50
Most frequent serious events
EventAtenololLosartan
Pneumothorax NOSRespiratory, thoracic and mediastinal disorders3/3035/305
PneumoniaInfections and infestations4/3031/305
DehydrationMetabolism and nutrition disorders3/3030/305
DepressionPsychiatric disorders3/3031/305
Valvular heart disease NOSCardiac disorders0/3033/305
AnxietyPsychiatric disorders2/3030/305
Atrial fibrillationCardiac disorders0/3032/305
Chest painGeneral disorders1/3032/305
PregnancyPregnancy, puerperium and perinatal conditions1/3032/305
AgitationPsychiatric disorders1/3032/305
Most frequent other events
Showing 10 of 172
Most frequent other events
EventAtenololLosartan
HeadacheNervous system disorders31/30318/305
DizzinessNervous system disorders29/30317/305
FatigueGeneral disorders18/30311/305
Chest painGeneral disorders16/30317/305
SyncopeNervous system disorders13/3039/305
NightmareGeneral disorders7/30313/305
MyalgiaMusculoskeletal and connective tissue disorders3/30312/305
InsomniaPsychiatric disorders10/30312/305
AgitationPsychiatric disorders11/3033/305
PalpitationsCardiac disorders9/30310/305

Baseline characteristics

Age, Continuous
Age, Continuous(years)AtenololLosartanTotal
Mean11.5 ± 6.511.0 ± 6.211.2 ± 6.3
Age, Customized
Age, Customized(participants)AtenololLosartanTotal
Young adult7675151
Child227230457
Sex: Female, Male
Sex: Female, Male(Participants)AtenololLosartanTotal
Female123119242
Male180186366
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)AtenololLosartanTotal
Hispanic or Latino364682
Not Hispanic or Latino266259525
Unknown or Not Reported101
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)AtenololLosartanTotal
White266260526
Black212546
Asian61016
Other101020
Presence of causal FBN1 mutation
Presence of causal FBN1 mutation(participants)AtenololLosartanTotal
Yes9388181
No91524
Unknown201202403
Family history of Marfan
Family history of Marfan(participants)AtenololLosartanTotal
Yes180181361
No115109224
Unknown81523
Maximum aortic-root diameter, cm
Maximum aortic-root diameter, cm(centimeter)AtenololLosartanTotal
Mean3.4 ± 0.73.4 ± 0.73.4 ± 0.7

8 further baseline measures are reported on the registry.

08

Study locations

26 sites
  • Cedars-Sinai Medical Center
    Los Angeles, California 90048, United States
  • Lucile Packard Children's Hospital
    Palo Alto, California 94304, United States
  • Rady Children's Hospital / UCSD
    San Diego, California 92123, United States
  • Stanford University School of Medicine
    Stanford, California 94305, United States
  • Children's Memorial Hospital
    Chicago, Illinois 60614, United States
  • Johns Hopkins University School of Medicine
    Baltimore, Maryland 21205, United States
  • Children's Hospital Boston
    Boston, Massachusetts 02115, United States
  • Children's Hospital of Minnesota - St. Paul
    Saint Paul, Minnesota 55102, United States
  • Washington University School of Medicine
    Saint Louis, Missouri 63110, United States
  • Weill Medical College of Cornell University
    New York, New York 10021, United States
  • Mount Sinai Medical Center
    New York, New York 10029, United States
  • Columbia College of Physicians and Surgeons
    New York, New York 10032, United States
  • Duke University Medical Center
    Durham, North Carolina 27710, United States
  • Brody School of Medicine at East Carolina University
    Greenville, North Carolina 27834, United States
  • Wake Forest University Baptist Medical Center
    Winston-Salem, North Carolina 27157, United States
  • Cincinnati Children's Hospital Medical Center
    Cincinnati, Ohio 45229, United States
  • Children's Hospital of Philadelphia
    Philadelphia, Pennsylvania 19104, United States
  • Hospital of the University of Pennsylvania
    Philadelphia, Pennsylvania 19104, United States
  • Children's Hospital of Pittsburgh
    Pittsburgh, Pennsylvania 15213, United States
  • Medical University of South Carolina
    Charleston, South Carolina 29425, United States
  • Vanderbilt University Medical Center
    Nashville, Tennessee 37212, United States
  • Texas Children's Hospital
    Houston, Texas 77030, United States
  • Primary Children's Medical Center
    Salt Lake City, Utah 84113, United States
  • Seattle Children's Hospital
    Seattle, Washington 98105, United States
  • Ghent University Hospital
    Ghent, Gent 185 9000, Belgium
  • Hospital for Sick Children
    Toronto, Ontario M5G 1X8, Canada
09

References and documents

Publications

  • Hoskoppal A, Menon S, Trachtenberg F, Burns KM, De Backer J, Gelb BD, Gleason M, James J, Lai WW, Liou A, Mahony L, Olson AK, Pyeritz RE, Sharkey AM, Stylianou M, Wechsler SB, Young L, Levine JC, Tierney ESS, Lacro RV, Bradley TJ; Pediatric Heart Network Investigators. Predictors of Rapid Aortic Root Dilation and Referral for Aortic Surgery in Marfan Syndrome. Pediatr Cardiol. 2018 Oct;39(7):1453-1461. doi: 10.1007/s00246-018-1916-6. Epub 2018 Jun 11. PubMed 29948025 ↗
  • Lacro RV, Dietz HC, Sleeper LA, Yetman AT, Bradley TJ, Colan SD, Pearson GD, Selamet Tierney ES, Levine JC, Atz AM, Benson DW, Braverman AC, Chen S, De Backer J, Gelb BD, Grossfeld PD, Klein GL, Lai WW, Liou A, Loeys BL, Markham LW, Olson AK, Paridon SM, Pemberton VL, Pierpont ME, Pyeritz RE, Radojewski E, Roman MJ, Sharkey AM, Stylianou MP, Wechsler SB, Young LT, Mahony L; Pediatric Heart Network Investigators. Atenolol versus losartan in children and young adults with Marfan's syndrome. N Engl J Med. 2014 Nov 27;371(22):2061-71. doi: 10.1056/NEJMoa1404731. Epub 2014 Nov 18. PubMed 25405392 ↗
  • Lacro RV, Guey LT, Dietz HC, Pearson GD, Yetman AT, Gelb BD, Loeys BL, Benson DW, Bradley TJ, De Backer J, Forbus GA, Klein GL, Lai WW, Levine JC, Lewin MB, Markham LW, Paridon SM, Pierpont ME, Radojewski E, Selamet Tierney ES, Sharkey AM, Wechsler SB, Mahony L; Pediatric Heart Network Investigators. Characteristics of children and young adults with Marfan syndrome and aortic root dilation in a randomized trial comparing atenolol and losartan therapy. Am Heart J. 2013 May;165(5):828-835.e3. doi: 10.1016/j.ahj.2013.02.019. Epub 2013 Mar 26. PubMed 23622922 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 7, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00429364
Lead sponsor
Carelon Research
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), FDA Office of Orphan Products Development, National Marfan Foundation
Responsible party
Sponsor
First posted
Jan 31, 2007
Start date
Jan 2007
Primary completion
Feb 2014
Completion
Feb 2014
Results posted
Apr 1, 2015
Last update
Mar 7, 2025

Study contacts

Ron Lacro, MD
principal investigator · Boston Children's Hospital

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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