Randomized, Double-blind Study for the Evaluation of the Effect of Losartan Versus Placebo on Aortic Root Dilatation in Patients With Marfan Syndrome Under Treatment With Beta-blockers

Study Overview
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Brief Summary
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To study the effect of losartan (an angiotensin receptor blocker-ARB) on aortic root growth in patients with Marfan syndrome, already treated with beta-blockers (BB). The effect of losartan will be compared to placebo. Losartan or placebo will be added to the treatment regimen in a two-step up-titration scheme over 2 weeks. Start doses of Losartan will be 25 mg for subjects under 50kg of weight and 50mg if the weight is over 50kg. Uptitration will be guided by the tolerance of the drug by the patients. Patients will be contacted by phone call for assessment of side-effects before second step of uptitration. Daily maximal doses of Losartan will be 50mg for subjects under 50kg of weight and 100mg if the weight is over 50kg

Official Title
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Randomized, Double-blind Study for the Evaluation of the Effect of Losartan Versus Placebo on Aortic Root Dilatation in Patients With Marfan Syndrome Under Treatment With Beta-blockers

Conditions
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Marfan Syndrome

Intervention / Treatment
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* Drug: Losartan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients > 10 years Diagnosis of MFS, according to the Ghent criteria and/or genetically proven FBN1 mutations or linkage Consent obtained (written) either for the patient and for his/her parents (<18y Z-score of the aorta at the level of the sinus of Valsalva ≥2 (BSA adjusted) ARB naïve patients Exclusion Criteria: Poor echocardiographic window,limiting the accurate measurement of the aortic root Contra-indication for ARB: Bilateral renal artery stenosis, renal function abnormalities (creatinine above normal for age), hyperkalemia Intolerance for ARB (eg angioedema) Pregnancy or breast feeding women Absence of effective contraception Liver function abnormalities Heart Failure Patients included in other clinical trial

Ages Eligible for Study
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Minimum Age: 10 Years

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Losartan | Drug: Losartan<br>* Daily maximal doses of Losartan will be 50mg for subjects under 50kg of weight and 100mg if the weight is over 50kg<br>|
| Placebo Comparator: 2<br>Placebo | Drug: Placebo<br>* Daily placebo capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The decrease of rate of aortic root growth measured by echocardiography at level of sinuses of Valsalva. The measure will be expressed in mm of growth per year and as Z-score. |  | At baseline and after 6 months, 1, 2 and 3 years follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparative arterial stiffness |  | At baseline and after 6 months, 1, 2 and 3 years follow-up | 
| Evaluation of progression of aortic regurgitation |  | At baseline and after 6 months, 1, 2 and 3 years follow-up | 
| Aortic dissection incidence |  | At baseline and after 6 months, 1, 2 and 3 years follow-up | 
| Aortic root surgery |  | At baseline and after 6 months, 1, 2 and 3 years follow-up | 
| Progression of mitral regurgitation |  | At baseline and after 6 months, 1, 2 and 3 years follow-up | 
| Left ventricular size and function |  | At baseline and after 6 months, 1, 2 and 3 years follow-up | 
| Skeletal and somatic traits |  | At baseline and after 6 months, 1, 2 and 3 years follow-up | 
| Quality of life |  | At baseline and after 6 months, 1, 2 and 3 years follow-up | 
| Genetic polymorphisms affecting clinical symptoms and response to treatment |  | End of study | 
| Death |  | At baseline and after 6 months, 1, 2 and 3 years follow-up | 
| Aortic stiffness as assessed by MRI |  | At baseline and after 1 year and 3 years follow-up |