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 - Full Text View

Sponsor:	University Hospital, Ghent
Collaborator:	Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT)
Information provided by:	University Hospital, Ghent
ClinicalTrials.gov Identifier:	NCT00782327

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 III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
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:

Genetics Home Reference related topics: Marfan syndrome

MedlinePlus related topics: Marfan Syndrome

Drug Information available for: Losartan Losartan potassium

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
1: Experimental 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
2: Placebo Comparator 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
Principal Investigator: Bart Loeys, MD, PhD

Sponsors and Collaborators

University Hospital, Ghent

Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT)

Investigators

Principal Investigator:	Julie De Backer, MD, PhD	University Hospital, Ghent
Principal Investigator:	Bart Loeys, 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 ( Julie De Backer )
Study ID Numbers:	2008/503
Study First Received:	October 29, 2008
Last Updated:	October 13, 2009
ClinicalTrials.gov Identifier:	NCT00782327 History of Changes
Health Authority:	Belgium: Federal Agency for Medicinal Products and Health Products; Belgium: Institutional Review Board

Additional relevant MeSH terms:

Neurotransmitter Agents
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Bone Diseases
Musculoskeletal Abnormalities
Limb Deformities, Congenital
Pathologic Processes
Musculoskeletal Diseases
Therapeutic Uses
Syndrome
Abnormalities, Multiple
Bone Diseases, Developmental
Connective Tissue Diseases
Adrenergic beta-Antagonists

Cardiovascular Diseases
Anti-Arrhythmia Agents
Congenital Abnormalities
Losartan
Heart Diseases
Disease
Cardiovascular Abnormalities
Cardiovascular Agents
Antihypertensive Agents
Marfan Syndrome
Pharmacologic Actions
Angiotensin II Type 1 Receptor Blockers
Genetic Diseases, Inborn
Adrenergic Antagonists
Heart Defects, Congenital

ClinicalTrials.gov processed this record on February 04, 2010