Rationale and design of a randomized clinical trial (Marfan Sartan) of angiotensin II receptor blocker therapy versus placebo in individuals with Marfan syndrome.
BACKGROUND
Recent studies have demonstrated that blockade of the angiotensin II type 1 receptor with losartan decreases aortic damage in an animal model of Marfan syndrome (a KI mouse model with a pathogenic mutation in the gene coding for fibrillin-1).


OBJECTIVE
To demonstrate a beneficial effect of losartan on aortic dilatation when added to optimal therapy in patients with Marfan syndrome.


METHODS
This is a multicentre, randomized, placebo-controlled, double-blind, clinical trial with a 2-year inclusion period and a 3-year follow-up period. Aortic root diameter will be measured using two-dimensional echocardiography. Secondary endpoints will include incidence of aortic dissection, aortic root surgery, death, quality of life, tolerance and compliance with treatments. We aim to enroll a total of 300 patients aged > or =10 years who fulfil the Ghent criteria for Marfan syndrome. Analyses will be based on intention to treat.


CONCLUSIONS
The results of this clinical trial could lead to profound modification of the management of aortic risk and complications in patients with Marfan syndrome and possibly in patients with thoracic aortic aneurysms of other aetiologies.
Detaint
Delphine
D
Centre de référence pour le syndrome de Marfan et apparentés, hôpital Bichat, Paris, France.
Aegerter
Philippe
P
Tubach
Florence
F
Hoffman
Isabelle
I
Plauchu
Henri
H
Dulac
Yves
Y
Faivre
Laurence Olivier
LO
Delrue
Marie-Ange
MA
Collignon
Patrick
P
Odent
Sylvie
S
Tchitchinadze
Maria
M
Bouffard
Catherine
C
Arnoult
Florence
F
Gautier
Mathieu
M
Boileau
Catherine
C
Jondeau
Guillaume
G
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D001014:Aortic Aneurysm / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004311:Double-Blind Method; D005602:France; D006801:Humans; D019808:Losartan / Q000627:therapeutic use*; D008382:Marfan Syndrome / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D051379:Mice; D015990:Placebo Effect; D012107:Research Design; D016896:Treatment Outcome; D014463:Ultrasonography
D047228:Angiotensin II Type 1 Receptor Blockers; D019808:Losartan