AARDVARK (Aortic Aneurysmal Regression of Dilation: Value of ACE-Inhibition on RisK)

Overview

Abdominal aortic aneurysms (AAA) are balloon-like swellings of the body's main blood vessel (aorta) as it courses through the abdomen. As a result of the National Aneurysm Screening programme many more of these will be detected. Small AAAs grow slowly and remain a benign condition until the diameter exceeds 2-3 times the diameter of the normal aorta (about 5.5cm in size), when operative repair of the aneurysm is recommended avoiding the potentially fatal event of bursting and bleeding (aneurysm rupture). It is therefore important to identify a strategy to prevent aneurysm growth. There is a suggestion that the use of a specific drug class, angiotensin converting enzyme (ACE) inhibitors, may reduce the risk of rupture of the larger aneurysms. This trial will assess whether an ACE inhibitor (perindopril) has aneurysm-related benefits, in patients with small AAAs at screening centres in the London area. The effects of perindopril versus a placebo(dummy) on AAA growth rates will be compared. In addition by comparing the effects of perindopril with the effects of equivalent blood pressure lowering with another non-ACE inhibitor class of drug (amlodipine) on aneurysm growth rate, we can see whether any benefits of perindopril are simply the result of lowering blood pressure. 225 Patients will be assigned to one of these 3 treatments by chance (randomisation).In addition to analysis of the effect of perindopril and blood pressure lowering,the effect of the treatments on quality of life will be assessed. Patients will return at 3-monthly intervals for an ultrasound scan and blood pressure measurements, with questionnaires regarding quality of life at the start and end of the 2-year research period. An ultrasound scan is a painless test that uses sound waves to create images of organs and structures inside your body.

Full Title of Study: “An Evaluation of the Effect of an Angiotensin-converting Enzyme (ACE) Inhibitor on the Growth Rate of Small Abdominal Aortic Aneurysms.”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Investigator)
  • Study Primary Completion Date: April 2015

Detailed Description

This trial will investigate the idea that an ACE-inhibitor reduces abdominal aortic aneurysm (AAA) growth rate, in a pilot 3-arm randomised controlled trial (i.e. the study treatment is chosen by random for each patient). The three interventions are ACE-inhibition with perindopril; equivalent blood pressure reduction with amlodipine (a calcium channel blocker) and a placebo tablet. By comparing the effects in the perindopril and amlodipine arms, this design will permit an evaluation of any blood pressure independent effects of perindopril. Pending results of this pilot trial, we plan to work with the local and National Aneurysm Screening programme to conduct a larger, definitive trial, to investigate the hypothesis that blood pressure reduction with an ACE-inhibitor slows the rate of small AAA growth preferentially compared with other antihypertensive agents. Secondary research questions in this trial are the effects of perindopril therapy on aneurysm-related death rates, other diseases possibly caused by an AAA and quality of life compared to similar blood pressure lowering effects with amlodipine and placebo.

Interventions

  • Drug: perindopril arginine
    • 10mgs orally daily for the duration of the trial
  • Drug: amlodipine 5mgs
    • 5 mgs taken orally daily for the duration of the trial
  • Drug: placebo
    • one daily

Arms, Groups and Cohorts

  • Active Comparator: perindopril
    • ACE inhibitor blood pressure lowering agent
  • Active Comparator: amlodipine
    • calcium channel blocker blood pressure lowering agent
  • Placebo Comparator: placebo
    • inactive substance identical in appearance to the othe two comparators

Clinical Trial Outcome Measures

Primary Measures

  • Change in the Growth Rate of Abdominal Aortic Aneurysm
    • Time Frame: Annual rate over the entire period of 24 month
    • Aneurysm growth rate over 2 years, estimated from the sequential AAA diameter measurements (external diameter measured in the longitudinal plane).

Secondary Measures

  • Number of Participants With Aneurysm Related Death
    • Time Frame: 24 months

Participating in This Clinical Trial

Inclusion Criteria

Willing and able to give written informed consent Men or women, aged at least 55 years With AAA 3 to 5.4 cm in diameter by internal or external measurement according to ultrasound A systolic BP <150mmHg (unless they require and are already receiving an ACE-inhibitor or amlodipine 10mg daily). Exclusion criteria:

Patients who are already required to take either an ACE-inhibitor or a calcium channel blocker or Angiotensin II blocker (ARB) who cannot be converted to diuretic therapy and/ora 5mg dose of amlodipine for control (ie SBP < 150mmHg) of their BP. Those with known renal artery stenosis (>50%), or with a serum creatinine of >180┬Ámol/L Those unable to give informed consent Those too frail to travel for 3-monthly surveillance will be excluded Any clinically significant medical condition which, in the opinion of the investigator, may interfere with the study results and or reduce life expectancy to < 2 years Participation in another trial of an investigational product or device within the previous 30 days Known allergy or sensitivity to perindopril or amlodipine Unable or unwilling to comply with the requirements of the study, in the opinion of the investigator.

Gender Eligibility: All

Minimum Age: 55 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Imperial College London
  • Collaborator
    • National Institute for Health Research, United Kingdom
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Janet Powell, MD, Study Director, Imperial College London
    • Colin Bicknell, FRCS, Study Director, Imperial College London
    • Deborah Ashby, PhD, Study Director, Imperial College London
    • Meryl E Davis, FRCS, Principal Investigator, Royal Free Hospital NHS Trust
    • Mathew Waltham, FRCS, Principal Investigator, Guys Hospital NHS trust
    • Neil Poulter, FRCP, Study Director, Imperial College London
    • Christopher Imray, FRCS, Principal Investigator, University Hospitals Coventry & Warwickshire
    • Dynesh Rittoo, FRCS, Principal Investigator, The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust
    • Ian Chetter, FRCS, Principal Investigator, Hull University Teaching Hospitals NHS Trust
    • Sohail Choksy, FRCS, Principal Investigator, East Suffolk and North Essex NHS Foundation Trust
    • Tim Lees, FRCS, Principal Investigator, The Newcastle Hospitals NHS Foundation Trust
    • Andrew Thompson, FRCS, Principal Investigator, York Teaching Hospital NHS Foundation Trust
    • Vince Smyth, FRCS, Principal Investigator, Manchester University NHS Foundation Trust
    • Shah Nawaz, FRCS, Principal Investigator, Sheffield Teaching Hospitals NHS Foundation Trust
    • Andrew Brown, FRCS, Principal Investigator, City Hospitals Sunderland NHS Foundation Trust
    • Felicity Meyer, FRCS, Principal Investigator, Norfolk and Norwich University Hospitals NHS Foundation Trust

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