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

This study is currently recruiting participants.
Verified February 2013 by University Hospital, Ghent
Sponsor:
Collaborator:
Agentschap voor Innovatie door Wetenschap en Technologie
Information provided by (Responsible Party):
University Hospital, Ghent
ClinicalTrials.gov Identifier:
NCT00782327
First received: October 29, 2008
Last updated: February 1, 2013
Last verified: February 2013

October 29, 2008
February 1, 2013
June 2009
December 2014   (final data collection date for primary outcome 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. [ Time Frame: At baseline and after 6 months, 1, 2 and 3 years follow-up ] [ Designated as safety issue: Yes ]
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. [ Time Frame: At 6 months, 1, 2 and 3 years follow-up ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00782327 on ClinicalTrials.gov Archive Site
  • Comparative arterial stiffness [ Time Frame: At baseline and after 6 months, 1, 2 and 3 years follow-up ] [ Designated as safety issue: Yes ]
  • Evaluation of progression of aortic regurgitation [ Time Frame: At baseline and after 6 months, 1, 2 and 3 years follow-up ] [ Designated as safety issue: Yes ]
  • Aortic dissection incidence [ Time Frame: At baseline and after 6 months, 1, 2 and 3 years follow-up ] [ Designated as safety issue: Yes ]
  • Aortic root surgery [ Time Frame: At baseline and after 6 months, 1, 2 and 3 years follow-up ] [ Designated as safety issue: Yes ]
  • Progression of mitral regurgitation [ Time Frame: At baseline and after 6 months, 1, 2 and 3 years follow-up ] [ Designated as safety issue: Yes ]
  • Left ventricular size and function [ Time Frame: At baseline and after 6 months, 1, 2 and 3 years follow-up ] [ Designated as safety issue: Yes ]
  • Skeletal and somatic traits [ Time Frame: At baseline and after 6 months, 1, 2 and 3 years follow-up ] [ Designated as safety issue: Yes ]
  • Quality of life [ Time Frame: At baseline and after 6 months, 1, 2 and 3 years follow-up ] [ Designated as safety issue: No ]
  • Genetic polymorphisms affecting clinical symptoms and response to treatment [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • Death [ Time Frame: At baseline and after 6 months, 1, 2 and 3 years follow-up ] [ Designated as safety issue: Yes ]
  • Aortic stiffness as assessed by MRI [ Time Frame: At baseline and after 1 year and 3 years follow-up ] [ Designated as safety issue: Yes ]
  • Comparative arterial stiffness [ Time Frame: At 6 months, 1, 2 and 3 years follow-up ] [ Designated as safety issue: Yes ]
  • Evaluation of progression of aortic regurgitation [ Time Frame: At 6 months, 1, 2 and 3 years follow-up ] [ Designated as safety issue: Yes ]
  • Aortic dissection incidence [ Time Frame: At 6 months, 1, 2 and 3 years follow-up ] [ Designated as safety issue: Yes ]
  • Aortic root surgery [ Time Frame: At 6 months, 1, 2 and 3 years follow-up ] [ Designated as safety issue: Yes ]
  • Progression of mitral regurgitation [ Time Frame: At 6 months, 1, 2 and 3 years follow-up ] [ Designated as safety issue: Yes ]
  • Left ventricular size and function [ Time Frame: At 6 months, 1, 2 and 3 years follow-up ] [ Designated as safety issue: Yes ]
  • Skeletal and somatic traits [ Time Frame: At 6 months, 1, 2 and 3 years follow-up ] [ Designated as safety issue: Yes ]
  • Quality of life [ Time Frame: At 6 months, 1, 2 and 3 years follow-up ] [ Designated as safety issue: No ]
  • Genetic polymorphisms affecting clinical symptoms and response to treatment [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • Death [ Time Frame: At 6 months, 1, 2 and 3 years follow-up ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
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
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

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

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Marfan Syndrome
  • Drug: Losartan
    Daily maximal doses of Losartan will be 50mg for subjects under 50kg of weight and 100mg if the weight is over 50kg
  • Drug: Placebo
    Daily placebo capsule
  • Experimental: 1
    Losartan
    Intervention: Drug: Losartan
  • Placebo Comparator: 2
    Placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
174
December 2014
December 2014   (final data collection date for primary outcome measure)

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
Both
10 Years and older
No
Contact: Sylvia De Nobele sylvia.denobele@ugent.be
Belgium
 
NCT00782327
2008/503
Yes
University Hospital, Ghent
University Hospital, Ghent
Agentschap voor Innovatie door Wetenschap en Technologie
Principal Investigator: Julie De Backer, MD, PhD University Hospital, Ghent
University Hospital, Ghent
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP