Marfan Syndrome | 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 research study
What is the primary objective of this study?
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
Who is eligible to participate?
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
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:LosartanDaily maximal doses of Losartan will be 50mg for subjects under 50kg of weight and 100mg if the weight is over 50kg
Drug:PlaceboDaily placebo capsule
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
Start Date: June 2009
Completed Date: December 2015
Phase: Phase 3
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
Study sponsors, principal investigator, and references
Principal Investigator: Julie De Backer, MD, PhD
Lead Sponsor: University Hospital, Ghent
Collaborator: Agentschap voor Innovatie door Wetenschap en Technologie