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

NCT00782327 | Completed Phase 3 DMC

• 1 other identifier: 2008/503
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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

Conditions

Marfan Syndrome

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Comparative arterial stiffness

  At baseline and after 6 months, 1, 2 and 3 years follow-up

• Evaluation of progression of aortic regurgitation

  At baseline and after 6 months, 1, 2 and 3 years follow-up

• Aortic dissection incidence

  At baseline and after 6 months, 1, 2 and 3 years follow-up

• Aortic root surgery

  At baseline and after 6 months, 1, 2 and 3 years follow-up

• Progression of mitral regurgitation

  At baseline and after 6 months, 1, 2 and 3 years follow-up

Study Arms (2)

1

EXPERIMENTAL

Losartan

Drug: Losartan

2

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Losartan DRUG

Daily maximal doses of Losartan will be 50mg for subjects under 50kg of weight and 100mg if the weight is over 50kg

1

Placebo DRUG

Daily placebo capsule

2

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Ghent: lead
• Agentschap voor Innovatie door Wetenschap en Technologie: collaborator

Study Sites (1)

University Hospital Ghent

Ghent, 9000, Belgium

Location

Related Links

• Website of the University Hospital Ghent

MeSH Terms

Conditions

Marfan Syndrome

Interventions

Losartan

Condition Hierarchy (Ancestors)

Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Study Officials

• Julie De Backer, MD, PhD

  University Hospital, Ghent

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2008
• First Posted: October 31, 2008
• Study Start: November 1, 2009
• Primary Completion: November 26, 2014
• Study Completion: November 26, 2014
• Last Updated: December 22, 2022

Record last verified: 2022-12

Locations

BE (1)