NCT00683124

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

Effects of Losartan vs. Nebivolol vs. the Association of Both on the Progression of Aortic Root Dilation in Marfan Syndrome (MFS) With FBN1 Gene Mutations.

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 291 (estimated)
• Sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia · Academic / Other
• Sex: All
• Age: 12 Months – 55 Years
• Healthy volunteers: Not accepted

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).

Detailed description

Marfan Syndrome is a rare disease (1:5000)(MIM#154700) caused by mutations of the Fibrillin 1 (FBN1) gene. The major clinical problem is aortic aneurysm with risk of dissection when root diameter is 5 cm. The investigators designed a clinical trial in which a new generation Beta-Blocker Nebivolol with expected effects on shear stress, heart rate and potential anti-stiffness benefits is compared to Losartan, and Angiotensin receptor blocker anti TGF-beta effects, and to the association of both molecules in patients with Marfan Syndrome. Nebivolol is a patented drug that differs chemically, pharmacologically and therapeutically from all other BBs. Nebivolol shows the highest selectivity for ß1 receptors among the currently available BBs, influences the arterial stiffness through an agonistic effect on ß2-receptors and preserves the arterial compliance. We expect a significantly lower progression of the Aortic Root Dilation in the arm of Nebivolol plus Losartan vs. single drug (primary end-point).The investigators further expect: decrease of arterial stiffness higher in the arm treated with both drugs than in solely Nebivolol or Losartan; a decrease of serum levels of active TGFb in both Losartan arms, a drug \& age-dependant variation of the expression of the mutated FBN1 gene. As for other end-points, the potential results are the improvement of valve function, hard events \& delay of surgical timing for the aortic root. The enrolment period will last 12 months, while the overall follow-up period will be of 4 years. An interim analysis for the primary outcome is programmed at month 24.

Conditions

• Marfan Syndrome

Interventions

Type	Name	Description
DRUG	Losartan and nebivolol	Nebivolol is administered orally as pills. It is given preferentially once a day in the morning or, if not well tolerated because of hypotension, the total daily dosage is given in two administrations. Losartan is administered orally as pills. It is given preferentially once a day or, if not well tolerated because of hypotension, the total daily dosage is given in two administrations
DRUG	Losartan	Losartan is administered orally as pills. It is given preferentially once a day or, if not well tolerated because of hypotension, the total daily dosage is given in two administrations
DRUG	Nebivolol	Nebivolol is administered orally as pills. It is given preferentially once a day in the morning or, if not well tolerated because of hypotension, the total daily dosage is given in two administrations

Timeline

• Start date: 2008-07-01
• Primary completion: 2013-07-01
• Completion: 2013-07-01
• First posted: 2008-05-23
• Last updated: 2011-07-22

Locations

1 site across 1 country: Italy