Study of the Efficacy of Losartan on Aortic Dilatation in Patients With Marfan Syndrome (MARFANSARTAN)

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

The purpose of this study is to evaluate if losartan limits aortic dilatation in patients with Marfan syndrome.

Condition or disease	Intervention/treatment	Phase
Marfan Syndrome	Drug: placebo; Drug: Losartan	Phase 3

Detailed Description:

Aim : evaluate the efficacy of losartan for limiting aortic dilatation in patients with marfan syndrome receiving standard therapy

Inclusion criteria :

10 years or older Marfan syndrome according to international criteria Signed informed consent

Non inclusion :

Previous surgery of the ascending aorta, or surgery planned Non echogenicity Contre-indication lactose Pregnancy on going or planned within 3 years Breast feeding Participation in another clinical study Non member of the social security or CMU

Number of subjects : the number of subjects (150 per group) is derived from the study from Shores et al (1994) demonstrating the benefit of beta-blockade in Marfan patient and uses a decrease by half of the aortic dilatation with losartan

Follow-up is 3 years, after inclusion period of 2 years. A total of 5 years is expected

Methods : randomised double blind vs placebo study. All French centres de competence for marfan syndrome and the centre de reference are participating in the study.

End points : main endpoint is evolution of normalised aortic diameter. Secondary endpoints include clinical events (cardiac surgery or aortic dissection, hospitalisation in cardiology department, death), tolerance of the drug, and quality of life.

Study Design

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	303 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, Investigator)
Primary Purpose:	Treatment
Official Title:	Multicenter, Randomised, Double Blind Study of the Efficacy of Losartan on Aortic Dilatation in Patients With Marfan Syndrome
Study Start Date :	September 2008
Actual Primary Completion Date :	January 2014
Actual Study Completion Date :	December 2014

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Placebo Comparator: A: Placebo; placebo	Drug: placebo; Cover key details of the intervention. Must be sufficiently detailed to distinguish between arms of a study (e.g., comparison of different dosages of drug) and/or among similar interventions (e.g., comparison of multiple implantable cardiac defibrillators). For example, interventions involving drugs may include dosage form, dosage, frequency and duration.
Active Comparator: B: Losartan; Losartan	Drug: Losartan; 50 mg/day if < weight 50 kg 100 mg/day if weight > 50 kg

Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. normalised aortic diameter at the level of the sinus of valsalva [ Time Frame: every six months ]

Secondary Outcome Measures :

1. cardiac surgery, hospitalisation in cardiology ward, death [ Time Frame: during the follow up ]

Eligibility Criteria

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	10 Years and older (Child, Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• 10 years or older
• Marfan syndrome according to international criteria Signed informed consent

Exclusion Criteria:

• Previous surgery of the ascending aorta, or surgery planned
• Non echogenicity
• Contre-indication lactose
• Pregnancy on going or planned within 3 years
• Breast feeding
• Participation in another clinical study
• Non member of the social security or CMU

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

France
Hôpital Bichat
Paris, France, 75018

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

Principal Investigator:	Guillaume JONDEAU, MD, PhD	Assistance Publique - Hôpitaux de Paris

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications of Results:

Detaint D, Aegerter P, Tubach F, Hoffman I, Plauchu H, Dulac Y, Faivre LO, Delrue MA, Collignon P, Odent S, Tchitchinadze M, Bouffard C, Arnoult F, Gautier M, Boileau C, Jondeau G. Rationale and design of a randomized clinical trial (Marfan Sartan) of angiotensin II receptor blocker therapy versus placebo in individuals with Marfan syndrome. Arch Cardiovasc Dis. 2010 May;103(5):317-25. doi: 10.1016/j.acvd.2010.04.008. Epub 2010 Jul 1.

Milleron O, Arnoult F, Ropers J, Aegerter P, Detaint D, Delorme G, Attias D, Tubach F, Dupuis-Girod S, Plauchu H, Barthelet M, Sassolas F, Pangaud N, Naudion S, Thomas-Chabaneix J, Dulac Y, Edouard T, Wolf JE, Faivre L, Odent S, Basquin A, Habib G, Collignon P, Boileau C, Jondeau G. Marfan Sartan: a randomized, double-blind, placebo-controlled trial. Eur Heart J. 2015 Aug 21;36(32):2160-6. doi: 10.1093/eurheartj/ehv151. Epub 2015 May 2.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Jiang P, Loyau S, Tchitchinadze M, Ropers J, Jondeau G, Jandrot-Perrus M. Inhibition of Glycoprotein VI Clustering by Collagen as a Mechanism of Inhibiting Collagen-Induced Platelet Responses: The Example of Losartan. PLoS One. 2015 Jun 8;10(6):e0128744. doi: 10.1371/journal.pone.0128744. eCollection 2015.

Responsible Party:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT00763893 History of Changes
Other Study ID Numbers:	P060210; 2006-006112-30 ( EudraCT Number )
First Posted:	October 1, 2008
Last Update Posted:	November 4, 2015
Last Verified:	October 2015

Keywords provided by Assistance Publique - Hôpitaux de Paris:

Marfan syndrome; Angiotensin II Type 1 Receptor Blockers; Aortic Aneurysm, Thoracic

Additional relevant MeSH terms:

Syndrome; Marfan Syndrome; Arachnodactyly; Disease; Pathologic Processes; 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; Losartan; Angiotensin II Type 1 Receptor Blockers; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin Receptor Antagonists; Molecular Mechanisms of Pharmacological Action