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

Condition(s) targeted: Marfan Syndrome

Intervention: Losartan (Drug); Placebo (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: University Hospital, Ghent

Official(s) and/or principal investigator(s):
Julie De Backer, MD, PhD, Principal Investigator, Affiliation: University Hospital, Ghent
Bart Loeys, MD, PhD, Principal Investigator, Affiliation: University Hospital, Ghent

Overall contact:
Sylvia De Nobele, Email: sylvia.denobele@ugent.be

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: 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 design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: 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.

Secondary outcome:

Comparative arterial stiffness

Evaluation of progression of aortic regurgitation

Aortic dissection incidence

Aortic root surgery

Progression of mitral regurgitation

Left ventricular size and function

Skeletal and somatic traits

Quality of life

Genetic polymorphisms affecting clinical symptoms and response to treatment

Death

Aortic stiffness as assessed by MRI

Minimum age: 10 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Sylvia De Nobele, Email: sylvia.denobele@ugent.be

University Hospital Ghent, Ghent 9000, Belgium; Recruiting
Julie De Backer, MD, PhD, Principal Investigator
Bart Loeys, MD, PhD, Principal Investigator

Website of the University Hospital Ghent

Starting date: June 2009
Ending date: December 2014
Last updated: October 13, 2009