A Randomized, Open-label, LOSARTAN Therapy on the Progression of Aortic Root Dilation in Patients With Marfan Syndrome

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

Detailed Description
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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.

Official Title
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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

Conditions
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Marfan Syndrome

Intervention / Treatment
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* Drug: Losartan and Atenolol or Propranolol
* Drug: Atenolol or Propranolol


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: B<br>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 | Drug: Losartan and Atenolol or Propranolol<br>* 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.<br>* Other names: Cozaar and Tenormin or Inderal;|
| Active Comparator: A<br>The maximal dose of Atenolol or Propranolol is 150 mg/day for adult and 2 mg/Kg/day for children. | Drug: Atenolol or Propranolol<br>* The maximal dose of Atenolol or Propranolol is 150 mg/day for adult and 2 mg/Kg/day for children.<br>* Other names: Tenormin or Inderal;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Echocardiograms |  | 4 months |