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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

Phase 3
Completed
Conditions
Marfan Syndrome
Interventions
Drug: Placebo
Registration Number
NCT00782327
Lead Sponsor
University Hospital, Ghent
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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
22
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
2PlaceboPlacebo
1LosartanLosartan
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
Evaluation of progression of aortic regurgitationAt baseline and after 6 months, 1, 2 and 3 years follow-up
Quality of lifeAt baseline and after 6 months, 1, 2 and 3 years follow-up
Genetic polymorphisms affecting clinical symptoms and response to treatmentEnd of study
Aortic dissection incidenceAt baseline and after 6 months, 1, 2 and 3 years follow-up
Left ventricular size and functionAt baseline and after 6 months, 1, 2 and 3 years follow-up
Skeletal and somatic traitsAt baseline and after 6 months, 1, 2 and 3 years follow-up
Aortic stiffness as assessed by MRIAt baseline and after 1 year and 3 years follow-up
DeathAt baseline and after 6 months, 1, 2 and 3 years follow-up
Comparative arterial stiffnessAt baseline and after 6 months, 1, 2 and 3 years follow-up
Aortic root surgeryAt baseline and after 6 months, 1, 2 and 3 years follow-up
Progression of mitral regurgitationAt baseline and after 6 months, 1, 2 and 3 years follow-up

Trial Locations

Locations (1)

University Hospital Ghent

🇧🇪

Ghent, Belgium

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