A prospective, randomised, placebo-controlled, double blind, multi-centre study of the effects of Irbesartan on aortic dilatation in Marfan syndrome

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2010-019302-16-GB
• Date of registration: 17/08/2010
• Prospective Registration: Yes
• Primary sponsor: Royal Brompton and Harefield NHS Foundation Trust
• Public title: A prospective, randomised, placebo-controlled, double blind, multi-centre study of the effects of Irbesartan on aortic dilatation in Marfan syndrome
• Scientific title: A prospective, randomised, placebo-controlled, double blind, multi-centre study of the effects of Irbesartan on aortic dilatation in Marfan syndrome - The AIMS Study
• Date of first enrolment: 13/09/2010
• Target sample size: 490
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-019302-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: Single blind: Double blind: yes Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom

Contacts

• Name: Regualtory Compliance Manager
• Affiliation: Royal Brompton Hospital

• Name: Regualtory Compliance Manager
• Affiliation: Royal Brompton Hospital

Key inclusion & exclusion criteria

Inclusion criteria:
1. Clinically confirmed MFS using the Ghent diagnostic criteria
2. 2. Aorta dilated above the 95% normal confidence limits (using accepted methods)
3. Provision of informed consent
4. From 6 = to = 40 years of age inclusive

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Previous cardiac or aortic surgery
2. Planned cardiac or aortic surgery at the time of randomisation
3. Aortic diameter >=4.5cm
4. Haemodynamically significant, severe valvular disease (at the judgement of the treating clinician)
5. Heart failure, defined as left ventricular ejection fraction < 40%
6. Therapeutic use of ACE inhibitors/angiotensin-II receptor antagonist
7. Previous recorded adverse reaction to the trial medication (Irbesartan) or any ACE inhibitor/angiotensin-II receptor antagonist
8. Female patients who are pregnant, planning pregnancy or not using reliable contraception
9. Impaired renal function defined as estimated creatinine clearance <60ml/minute, or serum creatinine >150micromol/litre


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Marfan Syndrome

Intervention(s)

Trade Name: Aprovel
Product Name: Aprovel
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Irbesartan
CAS Number: 138402-11-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-
INN or Proposed INN: Irbesartan
CAS Number: 138402-11-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
INN or Proposed INN: Irbesartan
CAS Number: 138402-11-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-

Primary Outcome(s)

Primary end point(s): The primary outcome measure will be the absolute change in aortic root diameter per year measured by echocardiography. Echo measurements will be taken by transthoracic echocardiograms performed at baseline and annually thereafter in order to assess the annual change of aortic dilatation.

Main Objective: Does the angiotensin II receptor antagonist, Irbesartan, reduce the rate of aortic dilatation in patients with Marfan Syndrome compared to placebo?

Secondary Objective: • 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, death (all cause and classified by suspected cause), 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, weight, arm span and lower segment measurements.
• Fibrillin-1 mutation analysis will be performed in those patients whose mutation status is unknown.

Secondary ID(s)

ISRCTN90011794

2010GU001B

Source(s) of Monetary Support

British Heart Foundation

Ethics review

Status: Approved
Approval date:
Contact: