Clinical trial NCT00782327: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Marfan Syndrome
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
Collaborators: name: Agentschap voor Innovatie door Wetenschap en Technologie
First posted: 2008-10-31
Enrollment: 22
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility 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

Primary outcomes:
measure: 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.
timeFrame: At baseline and after 6 months, 1, 2 and 3 years follow-up
Secondary outcomes:
measure: Comparative arterial stiffness
timeFrame: At baseline and after 6 months, 1, 2 and 3 years follow-up
measure: Evaluation of progression of aortic regurgitation
timeFrame: At baseline and after 6 months, 1, 2 and 3 years follow-up
measure: Aortic dissection incidence
timeFrame: At baseline and after 6 months, 1, 2 and 3 years follow-up
measure: Aortic root surgery
timeFrame: At baseline and after 6 months, 1, 2 and 3 years follow-up
measure: Progression of mitral regurgitation
timeFrame: At baseline and after 6 months, 1, 2 and 3 years follow-up
measure: Left ventricular size and function
timeFrame: At baseline and after 6 months, 1, 2 and 3 years follow-up
measure: Skeletal and somatic traits
timeFrame: At baseline and after 6 months, 1, 2 and 3 years follow-up
measure: Quality of life
timeFrame: At baseline and after 6 months, 1, 2 and 3 years follow-up
measure: Genetic polymorphisms affecting clinical symptoms and response to treatment
timeFrame: End of study
measure: Death
timeFrame: At baseline and after 6 months, 1, 2 and 3 years follow-up
measure: Aortic stiffness as assessed by MRI
timeFrame: At baseline and after 1 year and 3 years follow-up
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: University Hospital Ghent
Study officials:
affiliation: University Hospital, Ghent
name: Julie De Backer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: