The Ghent Marfan Trial--a randomized, double-blind placebo controlled trial with losartan in Marfan patients treated with β-blockers.
BACKGROUND
Aortic root dilation, dissection and rupture are major clinical problems in Marfan syndrome (MFS). Although β-blockers remain the standard of preventive treatment, preliminary results from animal studies and a selected group of severely affected MFS children show significant benefit from treatment with losartan, an angiotensin II receptor blocker with TGF-β inhibiting potential. Large-scale human trials are now needed to confirm these results. This trial aims to evaluate the combined effect of both drugs.


METHODS
We are conducting a prospective randomized placebo controlled double blind phase III study aiming to include 174 MFS patients (age ≥ 10 years and z-score ≥ 2). Patients already taking β-blockers are randomized for weight-adjusted treatment with losartan versus placebo. The primary endpoint is decrease in aortic root growth rate. Secondary endpoints are aortic dissection/surgery, progression of aortic/mitral regurgitation, arterial stiffness, left ventricular systolic/diastolic function, quality of life and genetic modifiers. Echocardiography, vascular echo-Doppler and quality of life assessment will be performed at baseline and at 6-monthly follow-ups for 3 years. MRI evaluation will be performed at baseline and at the end of the trial.


CONCLUSIONS
This trial will study new therapeutic strategies for the prevention of serious cardiovascular complications in MFS. The uniqueness in our trial is that the additive effect of losartan and β-blocker will be evaluated in a large spectrum of disease severity. A combination of ultrasound and MRI will allow detailed evaluation of anatomic and functional properties of the aorta and left ventricle.
Center for Medical Genetics, University Hospital Ghent, Belgium.
Katarina
K
Möberg
Sylvia
S
De Nobele
Dan
D
Devos
Els
E
Goetghebeur
Patrick
P
Segers
Bram
B
Trachet
Chris
C
Vervaet
Marjolijn
M
Renard
Paul
P
Coucke
Bart
B
Loeys
Anne
A
De Paepe
Julie
J
De Backer
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001530:Belgium / Q000453:epidemiology; D002648:Child; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008382:Marfan Syndrome / Q000188:drug therapy* / Q000453:epidemiology*; D008875:Middle Aged; D010919:Placebos; D011446:Prospective Studies; D055815:Young Adult
D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D010919:Placebos; D019808:Losartan