title: A prospective, randomized, placebo-controlled, double-blind, multicenter study of the effects of irbesartan on aortic dilatation in Marfan syndrome (AIMS trial): study protocol.
abstract: BACKGROUND
  Cardiovascular complications are the leading cause of mortality and morbidity in Marfan syndrome (MFS), a dominantly inherited disorder caused by mutations in the gene that encodes fibrillin-1. There are approximately 18,000 patients in the UK with MFS. Current treatment includes careful follow-up, beta blockers, and prophylactic surgical intervention; however, there is no known treatment which effectively prevents the rate of aortic dilatation in MFS. Preclinical, neonatal, and pediatric studies have indicated that angiotensin receptor blockers (ARBs) may reduce the rate of aortic dilatation. This trial will investigate the effects of irbesartan on aortic dilatation in Marfan syndrome.
  
  
  METHODS
  The Aortic Irbesartan Marfan Study (AIMS) is an investigator-led, prospective, randomized, placebo-controlled, double-blind, phase III, multicenter trial. Currently, 26 centers in the UK will recruit 490 clinically confirmed MFS patients (aged ≥6 to ≤40 years) using the revised Ghent diagnostic criteria. Patients will be randomized to irbesartan or placebo. Aortic root dilatation will be measured by transthoracic echocardiography at baseline and annually thereafter. The primary outcome is the absolute change in aortic root diameter per year measured by echocardiography. The follow-up period will be a minimum of 36 months with an expected mean follow-up period of 48 months.
  
  
  CONCLUSIONS
  This is the first clinical trial to evaluate the ARB irbesartan versus placebo in reducing the rate of aortic root dilatation in MFS. Not only will this provide useful information on the safety and efficacy of ARBs in MFS, it will also provide a rationale basis for potentially lifesaving therapy for MFS patients.
  
  
  BACKGROUND
  ISRCTN, 90011794.
authors.affiliation: The Heart Hospital, University College London Hospitals NHS Foundation Trust, 16-18 Westmoreland Street, London W1G 8PH, UK. michael.mullen@uclh.nhs.uk.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mullen
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Flather
authors.forename: Xu Yu
authors.initials: XY
authors.lastname: Jin
authors.forename: William G
authors.initials: WG
authors.lastname: Newman
authors.forename: Guliz
authors.initials: G
authors.lastname: Erdem
authors.forename: David
authors.initials: D
authors.lastname: Gaze
authors.forename: Oswaldo
authors.initials: O
authors.lastname: Valencia
authors.forename: Winston
authors.initials: W
authors.lastname: Banya
authors.forename: Claire E
authors.initials: CE
authors.lastname: Foley
authors.forename: Anne
authors.initials: A
authors.lastname: Child
mesh_terms: D000293:Adolescent; D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001011:Aorta / Q000000981:diagnostic imaging / Q000187:drug effects*; D001014:Aortic Aneurysm / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D002648:Child; D002985:Clinical Protocols; D004108:Dilatation, Pathologic; D004311:Double-Blind Method; D006801:Humans; D000077405:Irbesartan; D008382:Marfan Syndrome / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D011446:Prospective Studies; D012107:Research Design; D013777:Tetrazoles / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014463:Ultrasonography; D006113:United Kingdom; D055815:Young Adult
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000077405:Irbesartan