BACKGROUND: Marfan syndrome (MFS) is one of the most common systemic disorders 
of connective tissue with the incidence of approximately 2-3 per 10 000 
individuals. Aortic disease, leading to progressive aneurysmal dilatation and 
dissection is the main cause of morbidity and mortality of Marfan patients. 
Current treatment (e.g. beta blockers and elective surgery) does postpone but 
cannot prevent aortic complications in these patients. Recent studies have found 
transforming growth factor beta (TGF beta) to be involved in the aortic aneurysm 
formation. Losartan, an angiotensin II type 1 receptor blocker inhibits TGFbeta 
in a mouse model of Marfan syndrome leading to inhibition of aortic growth. The 
main objective of this trial is to assess whether losartan treatment leads to a 
clinically relevant decrease of aortic dilatation in adult patients with Marfan 
syndrome.
METHODS/DESIGN: COMPARE study (COzaar in Marfan Patients Reduces aortic 
Enlargement) is an open-label, randomized, controlled trial with blinded 
end-points. Treatment with losartan will be compared with no additional 
treatment after 3 years of follow-up. We will enroll 330 patients with MFS who 
will be randomly assigned to receive losartan or not. Patients taking 
beta-blockers will continue taking their standard treatment. The primary 
end-point is the largest change in aortic diameter at any aortic level measured 
by means of MRI. Secondary end-points are change in mortality, incidence of 
dissection, elective aortic surgery, aortic volume, aortic stiffness and 
ventricular function. We will also investigate gene and protein expression 
change in the skin under losartan therapy and create prediction models for 
losartan-treatment response and aortic dilatation.
DISCUSSION: The COMPARE study will provide important evidence of effects of 
losartan treatment in adult Marfan patient population. We expect losartan to 
significantly reduce the occurrence and progression of aortic dilatation. This 
trial investigates a wide spectrum of clinical, genetic and biochemical effects 
of losartan aiming to provide further insight in the pathogenesis and treatment 
of Marfan syndrome.
TRIAL REGISTRATION: Netherlands Trial Register NTR1423.