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

University Hospital, Ghent22 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Marfan Syndrome

Interventions

Eligibility

Sex: ALLMin age: 10 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.