Clinical trial NCT00763893: Study of the Efficacy of Losartan on Aortic Dilatation in Patients With Marfan Syndrome
Official title: Multicenter, Randomised, Double Blind Study of the Efficacy of Losartan on Aortic Dilatation in Patients With Marfan Syndrome
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Marfan Syndrome
Keywords: Marfan syndrome
Angiotensin II Type 1 Receptor Blockers
Aortic Aneurysm, Thoracic
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2008-10-01
Enrollment: 303
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility 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

Primary outcomes:
measure: normalised aortic diameter at the level of the sinus of valsalva
timeFrame: every six months
Secondary outcomes:
measure: cardiac surgery, hospitalisation in cardiology ward, death
timeFrame: during the follow up
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Bichat
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Guillaume JONDEAU, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.