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

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. A Double Blind Comparison With Similar Blood Pressure Lowering Medication (Calcium Channel Blockade)and Placebo”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Single Group 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

  • Reduction growth rate of abdominal aortic aneurysm
    • Time Frame: Every three months over a 2 year period
    • 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.

Secondary Measures

  • effect of treatment with perindopril on aneurysm related death rates
    • Time Frame: 42 months
    • 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.

Participating in This Clinical Trial

Inclusion Criteria

  • All men or women, aged 60-85 years, with AAA <5.5 cm and with a systolic BP < 150 mmHg will be eligible for inclusion in the trial. For patients whose systolic BP is > 150 mmHg, treatment will be initiated with a diuretic Indapamide SR 1.5mgs by the principal investigator and/or amlodipine (5 mg daily) initiated by the general Practitioner. If the SBP subsequently falls to < 150 mmHg on this medication subjects would then be eligible for inclusion into the study.

Exclusion Criteria

  • Patients already receiving an ACE-inhibitor or amlodipine 10mg daily.
  • Patients with known renal artery stenosis (> 50%).
  • Patients who cannot be converted to diuretic therapy and/or lower doses of amlodipine.
  • Those unable to give informed consent and those too frail to travel for 3-monthly surveillance.

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, Principal Investigator, Imperial College Charing Cross
    • Colin Bucknell, MD, Principal Investigator, Imperial Colege St Marys
    • deborah Ashby, PhD, Study Director, Imperial college. Faculty of Medicine statistics
    • Meryl E davis, FRCS, Principal Investigator, Royal Free Hospital NHS Trust
    • Mathew M Thompson, MD, Principal Investigator, St Georges Hospital Medical School
    • Mathew Waltham, Principal Investigator, Guys Hospital NHS trust
    • Neil Poulter, FRCP, Study Director, Imperial College London

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