Nebivolol Versus Losartan Versus Nebivolol+Losartan Against Aortic Root Dilation in Genotyped Marfan Patients

• Status: Unknown status
• Trial end date: 2013-07-01
• Target enrollment: 0
• Participant gender: All

Summary

The major clinical problems in patients with Marfan Syndrome (MFS) are aortic root dilation (ARD), dissection and rupture. Although the available treatments (beta-blockers, BBs) improve the evolution of the disease, they do not protect MFS patients from progression of ARD and dissection. A key molecule that negatively influences cell growth, differentiation, survival and death in MFS is TGFb which is antagonised by existing drugs employed in the clinical practice, the Angiotensin II receptor blockers (ARB).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: IRCCS Policlinico S. Matteo
• Collaborators: Menarini Group; Merck Sharp & Dohme Corp.
• Treatments: Losartan; Nebivolol

Criteria

Inclusion Criteria:

• Diagnosis of MFS: Ghent criteria and genetically proven defect of the FBN1 gene

• Age: 12 months to 55 years

• BSA-adjusted aortic z score = or >2 measured at the level of the sinuses of Valsalva at baseline according to Roman's method, or absolute aortic root diameter >38mm for females and >40 mm for males

Exclusion Criteria:

• Prior aortic surgery and/or dissection

• Aortic root diameter at the level of the sinuses of Valsalva 5 cm

• Planned aortic surgery within 6 months of enrollment for a rate of ARD progression>5 mm/year even in pts with ARD less than 5 cm

• Clinical or molecular diagnosis of non-MFS connective tissue diseases sharing some features with MFS (Shprintzen-Goldberg syndrome or Loeys-Dietz syndromes)

• Un-renounceable therapeutic (systemic hypertension, arrhythmia, ventricular dysfunction, valve regurgitation) use of drugs such as ACE inhibitors, BBs, or calcium-channel blockers

• Known side-effects while taking an ARB or a BB

• Intolerance to ARB that resulted in termination of therapy

• Intolerance to BB that resulted in termination of therapy

• Renal dysfunction (creatinine level more than upper limit of age-related normal values)

• Diabetes mellitus

• Pregnancy or planned pregnancy within 48 months of enrollment

• Technical limitations for the imaging studies including poor acoustic windows with limits the accurate measurement of aortic root

• Asthma.