Evaluation of Effect of Angiotensin-converting Enzyme (ACE) Inhibitors on Small Aneurysm Growth Rate

Brief Title

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

Official Title

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

Brief Summary

      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.
    

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 Phase

Phase 2

Study Type

Interventional

Primary Outcome

Change in the Growth Rate of Abdominal Aortic Aneurysm

Secondary Outcome

 Number of Participants With Aneurysm Related Death

Condition

Abdominal Aortic Aneurysm

Intervention

perindopril arginine

Study Arms / Comparison Groups

 perindopril

Description:  ACE inhibitor blood pressure lowering agent

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

224

Start Date

September 2011

Completion Date

April 2015

Primary Completion Date

April 2015

Eligibility Criteria

        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.
      

Gender

All

Ages

55 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Janet Powell, MD, , 

Location Countries

United Kingdom

Location Countries

United Kingdom

NCT ID

NCT01118520

Organization ID

CRO1644

Secondary IDs

2010-020226-17

Responsible Party

Sponsor

Study Sponsor

Imperial College London

Collaborators

 National Institute for Health Research, United Kingdom

Study Sponsor

Janet Powell, MD, Study Director, Imperial College London

Verification Date

January 2021