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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Trial of Beta Blocker Therapy (Atenolol) Versus Angiotensin II Receptor Blocker Therapy (Losartan) in Individuals With Marfan Syndrome (A Trial Conducted by the Pediatric

Brief 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.

Detailed Summary:

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 stu
Sponsor: New England Research Institutes

Current Primary Outcome: Annual Rate of Change in Aortic Root (Sinuses of Valsalva) Body-surface-area-adjusted Z-score [ Time Frame: Up to 3 years following randomization. ]

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


Original Primary Outcome: Rate of change in aortic root (sinuses of Valsalva) body-surface-area-adjusted Z-score

Current Secondary Outcome:

  • Annual Rate of Change in Aortic Root (Sinuses of Valsalva) Absolute Dimension [ Time Frame: Up to 3 years following randomization. ]
    The rate of change in the absolute dimension of the aortic root over a 3-year period following randomization
  • Annual Rate of Change in Ascending-aorta-diameter Z Score, Adjusted by Body-surface-area. [ Time Frame: Up to 3 years following randomization. ]
  • Annual Rate of Change in the Absolute Diameter of the Ascending Aorta [ Time Frame: Up to 3 years following randomization. ]
  • Annual Rate of Change in Aortic-annulus-diameter Z Score, Adjusted by Body-surface Area [ Time Frame: Up to 3 years following randomization. ]
  • Annual Rate of Change in the Absolute Diameter of the Aortic Annulus [ Time Frame: Up to 3 years following randomization. ]
  • Annual Rate of Change in Total Aortic Proximal Regurgitant Jet Area Indexed to Body-surface-area [ Time Frame: Up to 3 years following randomization. ]
  • Annual Rate of Change in Weight [ Time Frame: Up to 3 years following randomization. ]
  • Annual Rate of Change in Weight-for-age Z-score [ Time Frame: Up to 3 years following randomization. ]
  • Annual Rate of Change in Weight-for-height Z-score [ Time Frame: Up to 3 years following randomization. ]
  • Annual Rate of Change in Height [ Time Frame: Up to 3 years following randomization. ]
  • Annual Rate of Change in Height-for-age Z-score [ Time Frame: Up to 3 years following randomization. ]
  • Annual Rate of Change in Body Mass Index [ Time Frame: Up to 3 years following randomization. ]
  • Annual Rate of Change in Body Mass Index for Age Z-score [ Time Frame: Up to 3 years following randomization. ]
  • Annual Rate of Change in Arm Span to Height Ratio [ Time Frame: Up to 3 years following randomization. ]
  • Annual Rate of Change in Upper to Lower Segment Ratio [ Time Frame: Up to 3 years following randomization. ]
  • Number of Participants With Aortic Dissection. [ Time Frame: Up to 3 years following randomization. ]
  • Event Rate of Aortic Dissection. [ Time Frame: Up to 3 years following randomization. ]
    Percentage of participants who had aortic dissection over a 3-year period following randomization.
  • Number of Participants With Aortic-root Surgery. [ Time Frame: Up to 3 years following randomization. ]
  • Event Rate of Aortic-Root Surgery [ Time Frame: Up to 3 years following randomization. ]
    Percentage of participants who had aortic-root surgery over a 3-year period following randomization.
  • Number of Death. [ Time Frame: Up to 3 years following randomization. ]
  • Event Rate of Death [ Time Frame: Up to 3 years following randomization. ]
    Percentage of participants who died over a 3-year period following randomization.
  • 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. ]
  • Event Rate of the Composite Adverse Clinical Outcomes, Including Aortic Dissection, Aortic-root Surgery and Death. [ Time Frame: Up to 3 years following randomization. ]
    Percentage of participants who had aortic dissection, aortic-root surgery or death over a 3-year period following randomization
  • Adverse Drug Reactions Reported at the Baseline Visit [ Time Frame: At baseline ]
  • Adverse Drug Reactions Reported During Routine Follow-up Surveillance [ Time Frame: From 6 months to 3 years following randomization. ]


Original Secondary Outcome:

  • Rate of change in aortic root (sinuses of Valsalva) absolute dimension
  • Rate of change in ascending aorta and aortic annulus absolute dimension and body-surface-area-adjusted Z-score
  • Rate of change of aortic and mitral regurgitation
  • Aortic dissection, aortic root surgery, or death at 36 months after randomization
  • Time to first occurrence of aortic dissection, aortic root surgery, or death up to 36 months after randomization
  • Rate of change in Z-scores for left ventricular size, wall thickness, and function by two-dimensional and M-mode echocardiography
  • Rate of change of aortic root and ascending aortic elastic modulus and stiffness index
  • Rate of change in Z-scores for somatic growth, where available
  • Rate of change in weight and body mass index with covariate adjustment for age
  • Incidence of adverse drug reactions reported during routine surveillance


Information By: New England Research Institutes

Dates:
Date Received: January 29, 2007
Date Started: January 2007
Date Completion:
Last Updated: March 17, 2015
Last Verified: January 2014