Nebivolol Versus Losartan Versus Nebivolol+Losartan Against Aortic Root Dilation in Genotyped Marfan Patients (MaNeLo)
Marfan Syndrome
About this trial
This is an interventional treatment trial for Marfan Syndrome focused on measuring Marfan Syndrome, Losartan, Nebivolol, Transforming Growth Factor Beta, Aortic Root Dilation
Eligibility 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.
Sites / Locations
- IRCCS Foundation San Matteo HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Losartan
Nebivolol
Losartan+Nebivolol
Losartan administered as maximal tolerated dosage, not to exceed the maximal theorical dosage of 100 mg/day for adults and 1,6 mg/kg/die for children minor than 16 years.
Nebivolol administered as maximal tolerated dosage, not to exceed the maximal theorical dosage of 10 mg/day for adults and 0,16 mg/kg/die for children minor than 16 years.
Losartan administered as maximal tolerated dosage, not to exceed the maximal theorical dosage of 100 mg/day for adults and 1,6 mg/kg/die for children minor than 16 years. Nebivolol administered as maximal tolerated dosage, not to exceed the maximal theorical dosage of 10 mg/day for adults and 0,16 mg/kg/die for children minor than 16 years.