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

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 Overview

• Status: Completed
• Conditions: Marfan Syndrome
• Intervention / Treatment: Drug: Losartan; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sylvia De Nobele; Email: sylvia.denobele@ugent.be

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • University Hospital Ghent

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Collaborators: Agentschap voor Innovatie door Wetenschap en Technologie
• Investigators: Principal Investigator: Julie De Backer, MD, PhD, University Hospital, Ghent

Publications and helpful links

Helpful Links

• Website of the University Hospital Ghent

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2009
• Primary Completion (Actual): November 26, 2014
• Study Completion (Actual): November 26, 2014

Study Registration Dates

• First Submitted: October 29, 2008
• First Submitted That Met QC Criteria: October 29, 2008
• First Posted (Estimate): October 31, 2008

Study Record Updates

• Last Update Posted (Actual): December 22, 2022
• Last Update Submitted That Met QC Criteria: December 21, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Musculoskeletal Diseases; Connective Tissue Diseases; Bone Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Musculoskeletal Abnormalities; Abnormalities, Multiple; Bone Diseases, Developmental; Limb Deformities, Congenital; Syndrome; Marfan Syndrome; Arachnodactyly; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Losartan
• Other Study ID Numbers: 2008/503