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

Marfan Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00782327
• Other study ID #: 2008/503
• Status: Completed
• Phase: Phase 3
• Start date: November 1, 2009
• Est. completion date: November 26, 2014

Study information

• Verified date: December 2022
• Source: University Hospital, Ghent
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: November 26, 2014
• Est. primary completion date: November 26, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Marfan Syndrome
• Syndrome

Intervention

Drug:
• Losartan
Daily maximal doses of Losartan will be 50mg for subjects under 50kg of weight and 100mg if the weight is over 50kg
• Placebo
Daily placebo capsule

Locations

Country	Name	City	State
Belgium	University Hospital Ghent	Ghent

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Ghent	Agentschap voor Innovatie door Wetenschap en Technologie

Country where clinical trial is conducted

Belgium, 

Outcome

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

External Links

•   Website of the University Hospital Ghent