Official Title: “A Randomized, Open-Label, Active Control Trial to Evaluate the Effect of LOSARTAN Therapy on the Progression of Aortic Root Dilation in Patients With Marfan Syndrome”

To assess the efficacy of angiotensin II receptor blocker, Losartan, to prevent progressive dilation of aortic root in patients with Marfan syndrome.

Study Type: Interventional

Study Design: Prevention, Randomized, Open Label, Factorial Assignment, Safety/Efficacy Study

Study Primary Completion Date: February 2011

Marfan syndrome (MFS) is a multisystem connective tissue disorder of autosomal dominant inheritance1. The cardinal features are noted in the cardiovascular, ocular, and skeletal system. The most life-threatening complication of MFS is progressive aortic root dilation leading to aortic dissection or rupture. Losartan, an angiotensin II type I receptor (AT1) antagonist, is a drug already in clinical use for hypertension and type II diabetic nephropathy. A recent study showed that Losartan prevents aortic root dilation and lung problem in a mouse model of MFS. Therefore, the goals of this clinical trial are to examine the efficacy and safety of Losartan in patients with Marfan syndrome for aortic root dilation prevention.

Intervention(s) in this Clinical Trial

• Drug: Losartan and Atenolol or Propranolol
  • 50 mg of Atenolol once daily, 20 mg of Propranolol twice daily for adult and 1 mg/Kg/day for children. Losartan is 100 mg/day for adult and 50 mg/day for children.
• Drug: Atenolol or Propranolol
  • The maximal dose of Atenolol or Propranolol is 150 mg/day for adult and 2 mg/Kg/day for children.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: B
  • In combination therapy,the maximal dose of Losartan is 100 mg/day for adult and 50 mg/day for children. 50 mg of Atenolol once daily, 20 mg of Propranolol twice daily for adult and 1 mg/Kg/day for children
• Active Comparator: A
  • The maximal dose of Atenolol or Propranolol is 150 mg/day for adult and 2 mg/Kg/day for children.

Primary Measures

• Echocardiograms
  • Time Frame: 4 months
    Safety Issue?: No

Inclusion criteria

• Marfan syndrome with recognized aortic root dilation
• Patients must be older than one year of age
• Beta-blocker treatment at least three months
• Must sign an informed consent form

Exclusion criteria

• Prior to aortic root surgery
• Aortic root dimension more than 5.5cm
• Aortic surgery within 6 months
• Diabetes mellitus or liver and renal dysfunction or asthma
• Pregnancy
• Intolerance to Losartan therapy

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 1 Year

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Taiwan University Hospital

Overall Clinical Trial Officials and Contacts

Mei-Hwan Wu Principal Investigator National Taiwan University Hospital  

Information obtained from ClinicalTrials.gov on August 21, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00651235

Study ID Number: 200610030M

ClinicalTrials.gov Identifier: NCT00651235

Health Authority: Taiwan: Department of Health