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

An Evaluation of the Effect of an Angiotensin-converting Enzyme (ACE) Inhibitor on the Growth Rate of Small Abdominal Aortic Aneurysms.

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.

Study Overview

• Status: Completed
• Conditions: Abdominal Aortic Aneurysm
• Intervention / Treatment: Drug: perindopril arginine; Drug: amlodipine 5mgs; Drug: placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 224
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Bournemouth, United Kingdom, BH7 7DW
    • The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust
  • Colchester, United Kingdom, CO4 5JL
    • Colchester Hospital
  • Coventry, United Kingdom, CV2 2DX
    • University Hospital Coventry and Warwickshire
  • Hull, United Kingdom, HU3 2JZ
    • Hull Royal Infirmary
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital
  • London, United Kingdom, SE1 7EH
    • St Thomas' Hospital
  • London, United Kingdom, W21PG
    • St Mary's Hospital, Imperial College Healthcare NHS Trust
  • London, United Kingdom, W6 8RF
    • Charing Cross Hospital, Imperial College NHS Trust
  • Newcastle, United Kingdom, NE7 7DN
    • Freeman Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 >180µmol/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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: perindopril; ACE inhibitor blood pressure lowering agent	Drug: perindopril arginine; 10mgs orally daily for the duration of the trial; Other Names: coversyl arginine
Active Comparator: amlodipine; calcium channel blocker blood pressure lowering agent	Drug: amlodipine 5mgs; 5 mgs taken orally daily for the duration of the trial
Placebo Comparator: placebo; inactive substance identical in appearance to the othe two comparators	Drug: placebo; one daily

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Aneurysm Related Death	24 months

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• AARDVARK Publication

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2011
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: May 5, 2010
• First Submitted That Met QC Criteria: May 5, 2010
• First Posted (Estimate): May 6, 2010

Study Record Updates

• Last Update Posted (Actual): January 26, 2021
• Last Update Submitted That Met QC Criteria: January 5, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: abdominal aortic aneurysm; ACE Inhibition
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Aortic Diseases; Aneurysm; Aortic Aneurysm; Aortic Aneurysm, Abdominal; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Enzyme Inhibitors; Protease Inhibitors; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin-Converting Enzyme Inhibitors; Amlodipine; Perindopril
• Other Study ID Numbers: CRO1644; 2010-020226-17 (EudraCT Number); 08/109/02 (Other Grant/Funding Number: NIHR)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No