Title
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A Prospective, randomised, placebo-controlled double blind, multi-centre study of the effects of Irbesartan on aortic dilatation in Marfan syndrome
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Acronym
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The AIMS Study
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Study Aim
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To investigate the effects of Irbesartan on aortic dilatation in Marfan syndrome
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Study Design
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Investigator led, prospective, randomised, placebo-controlled double blind,Phase III, multi-centre study
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Eligibility Criteria
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Inclusion criteria:
Clinically confirmed MFS using the revised Ghent diagnostic criteria 2010, Provision of informed consent, from ≥ 6 to ≤ 40 years of age inclusive.
Exclusion criteria:
Previous cardiac or aortic surgery, Planned cardiac or aortic surgery, Aortic root Z score ≤0, Aortic diameter ≥4.5cm, Haemodynamically significant, severe valvular disease, Heart failure (defined as left ventricular ejection fraction < 40%), Therapeutic use of ACE inhibitors/angiotensin-II receptor antagonist, Previous recorded adverse reaction to the trial medication (Irbesartan), Female patient who is pregnant, planning pregnancy or not using reliable contraception, known impaired renal function.
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Treatment Schedule
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Drug:
3 treatment phases:
1) Run in Phase: 75mg open label Irbesartan (1 month) – All patients
2) Month 2: 150 mg Irbesartan/placebo o.d.
3) Month 3-up to max 60 months: 300mg Irbesartan/placebo o.d.
The proposed target doses are 300mg o.d. for patients >50kg and 150mg o.d. for patients <50kg.
Patients unable to tolerate the maximum dose will be down titrated accordingly.
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Sample size
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490 patients
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Randomisation
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1:1 randomisation to Irbesartan or placebo
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Outcome Measures
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Primary: Absolute change in aortic root diameter per year measured by echocardiography.
Secondary: Change in z score per year - where the z score is calculated on aortic root and body surface area (BSA), clinical events and requirement for surgery including aortic dissection confirmed on TOE, MRI or CT, aortic dissection requiring emergency surgery, aortic dissection requiring elective surgery, aortic dilatation requiring elective or emergency surgery, sudden death, cerebrovascular accident, cardiovascular death, aortic regurgitation requiring surgery, death during surgery for any of the above, left ventricular function determined by volumes and ejection fraction, left ventricular mass measurements, assessment of valvular function, cardiac rhythm and voltage, height, arm span and lower segment measurements, fibrillin-1 mutation analysis will be performed in those patients whose mutation status is unknown.
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Recruitment Period
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24 months
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Follow Up
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Minimum 36 – Maximum 60 months (average 48 months)
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Sponsor
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Royal Brompton and Harefield NHS Foundation Trust
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Sites
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See appendix 1.0
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