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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

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
History of Changes
  Purpose

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


Condition Intervention Phase
Marfan Syndrome
 Drug: Losartan
Drug: Placebo
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Marfan Syndrome
U.S. FDA Resources

Further study details as provided by University Hospital, Ghent:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 174
Study Start Date: June 2009
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Losartan
 Drug: Losartan
Daily maximal doses of Losartan will be 50mg for subjects under 50kg of weight and 100mg if the weight is over 50kg
Placebo Comparator: 2
Placebo
 Drug: Placebo
Daily placebo capsule

  Eligibility

Ages Eligible for Study:   10 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00782327

Contacts
Contact: Sylvia De Nobele sylvia.denobele@ugent.be

Locations
Belgium
University Hospital Ghent Recruiting
Ghent, Belgium, 9000
Principal Investigator: Julie De Backer, MD, PhD            
Sponsors and Collaborators
University Hospital, Ghent
Agentschap voor Innovatie door Wetenschap en Technologie
Investigators
Principal Investigator: Julie De Backer, MD, PhD University Hospital, Ghent
  More Information

Additional Information:
Website of the University Hospital Ghent  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: University Hospital, Ghent
ClinicalTrials.gov Identifier: NCT00782327     History of Changes
Other Study ID Numbers: 2008/503
Study First Received: October 29, 2008
Last Updated: February 1, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Belgium: Institutional Review Board

Additional relevant MeSH terms:
Marfan Syndrome
Arachnodactyly
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Abnormalities, Multiple
Congenital Abnormalities
Genetic Diseases, Inborn
Connective Tissue Diseases
Limb Deformities, Congenital
Musculoskeletal Abnormalities
 Adrenergic beta-Antagonists
Losartan
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on June 18, 2013