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

Phase 3

Completed

• Conditions: Marfan Syndrome
• Interventions: Drug: Placebo; Drug: Losartan

• Registration Number: NCT00782327
• Lead Sponsor: University Hospital, Ghent

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2008-10-29
• Study First Submitted QC: 2008-10-29
• Study First Posted: 2008-10-31
• Study Start: 2009-11-01
• Primary Completion: 2014-11-26
• Study Completion: 2014-11-26
• Status Verified: 2022-12
• Last Update Submitted: 2022-12-21
• Last Update Posted: 2022-12-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Placebo	Placebo
1	Losartan	Losartan

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Evaluation of progression of aortic regurgitation	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
Aortic dissection incidence	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
Aortic stiffness as assessed by MRI	At baseline and after 1 year and 3 years follow-up
Death	At baseline and after 6 months, 1, 2 and 3 years follow-up
Comparative arterial stiffness	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

Trial Locations

Locations (1)

University Hospital Ghent; 🇧🇪 Ghent, Belgium