Clinical Trial: Randomized, Double-blind Study for the Evaluation of the Effect of Losartan Versus Placebo on Aortic Root Dilatation in Patients With Marfan Syndrome Under Treatment With Beta-blockers

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Randomized, Double-blind Study for the Evaluation of the Effect of Losartan Versus Placebo on Aortic Root Dilatation in Patients With Marfan Syndrome Under Treatment With

Brief Summary:

To study the effect of losartan (an angiotensin receptor blocker-ARB) on aortic root growth in patients with Marfan syndrome, already treated with beta-blockers (BB). The effect of losartan will be compared to placebo. Losartan or placebo will be added to the treatment regimen in a two-step up-titration scheme over 2 weeks. Start doses of Losartan will be 25 mg for subjects under 50kg of weight and 50mg if the weight is over 50kg. Uptitration will be guided by the tolerance of the drug by the patients. Patients will be contacted by phone call for assessment of side-effects before second step of uptitration.

Daily maximal doses of Losartan will be 50mg for subjects under 50kg of weight and 100mg if the weight is over 50kg


Detailed Summary:
Sponsor: University Hospital, Ghent

Current Primary Outcome: The decrease of rate of aortic root growth measured by echocardiography at level of sinuses of Valsalva. The measure will be expressed in mm of growth per year and as Z-score. [ Time Frame: At baseline and after 6 months, 1, 2 and 3 years follow-up ]

Original Primary Outcome: The decrease of rate of aortic root growth measured by echocardiography at level of sinuses of Valsalva. The measure will be expressed in mm of growth per year and as Z-score. [ Time Frame: At 6 months, 1, 2 and 3 years follow-up ]

Current Secondary Outcome:

  • Comparative arterial stiffness [ Time Frame: At baseline and after 6 months, 1, 2 and 3 years follow-up ]
  • Evaluation of progression of aortic regurgitation [ Time Frame: At baseline and after 6 months, 1, 2 and 3 years follow-up ]
  • Aortic dissection incidence [ Time Frame: At baseline and after 6 months, 1, 2 and 3 years follow-up ]
  • Aortic root surgery [ Time Frame: At baseline and after 6 months, 1, 2 and 3 years follow-up ]
  • Progression of mitral regurgitation [ Time Frame: At baseline and after 6 months, 1, 2 and 3 years follow-up ]
  • Left ventricular size and function [ Time Frame: At baseline and after 6 months, 1, 2 and 3 years follow-up ]
  • Skeletal and somatic traits [ Time Frame: At baseline and after 6 months, 1, 2 and 3 years follow-up ]
  • Quality of life [ Time Frame: At baseline and after 6 months, 1, 2 and 3 years follow-up ]
  • Genetic polymorphisms affecting clinical symptoms and response to treatment [ Time Frame: End of study ]
  • Death [ Time Frame: At baseline and after 6 months, 1, 2 and 3 years follow-up ]
  • Aortic stiffness as assessed by MRI [ Time Frame: At baseline and after 1 year and 3 years follow-up ]


Original Secondary Outcome:

  • Comparative arterial stiffness [ Time Frame: At 6 months, 1, 2 and 3 years follow-up ]
  • Evaluation of progression of aortic regurgitation [ Time Frame: At 6 months, 1, 2 and 3 years follow-up ]
  • Aortic dissection incidence [ Time Frame: At 6 months, 1, 2 and 3 years follow-up ]
  • Aortic root surgery [ Time Frame: At 6 months, 1, 2 and 3 years follow-up ]
  • Progression of mitral regurgitation [ Time Frame: At 6 months, 1, 2 and 3 years follow-up ]
  • Left ventricular size and function [ Time Frame: At 6 months, 1, 2 and 3 years follow-up ]
  • Skeletal and somatic traits [ Time Frame: At 6 months, 1, 2 and 3 years follow-up ]
  • Quality of life [ Time Frame: At 6 months, 1, 2 and 3 years follow-up ]
  • Genetic polymorphisms affecting clinical symptoms and response to treatment [ Time Frame: End of study ]
  • Death [ Time Frame: At 6 months, 1, 2 and 3 years follow-up ]


Information By: University Hospital, Ghent

Dates:
Date Received: October 29, 2008
Date Started: June 2009
Date Completion: December 2015
Last Updated: June 2, 2015
Last Verified: June 2015