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

Condition(s) targeted: Abdominal Aortic Aneurysm

Intervention: perindopril arginine (Drug); amlodipine 5mgs (Drug); placebo (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Imperial College London

Official(s) and/or principal investigator(s):
Janet Powell, MD, Principal Investigator, Affiliation: Imperial College Charing Cross
Colin Bucknell, MD, Principal Investigator, Affiliation: Imperial Colege St Marys
deborah Ashby, PhD, Study Director, Affiliation: Imperial college. Faculty of Medicine statistics
Meryl E davis, FRCS, Principal Investigator, Affiliation: Royal Free Hospital NHS Trust
Mathew M Thompson, MD, Principal Investigator, Affiliation: St Georges Hospital Medical School
Mathew Waltham, Principal Investigator, Affiliation: Guys Hospital NHS trust

Overall contact:
Neil R Poulter, FRCP, Phone: 02075943446, Email: n.poulter@imperial.ac.uk

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.

Official title: 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 design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Primary outcome: reduction growth rate of abdominal aortic aneurysm

Secondary outcome: effect of treatment with perindopril on aneurysm related death rates

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.

Minimum age: 60 Years. Maximum age: 85 Years. Gender(s): Both.

Criteria:

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.

Neil R Poulter, FRCP, Phone: 02075943446, Email: n.poulter@imperial.ac.uk

University Hospital Coventry and Warwickshire, Coventry CV2 2DX, United Kingdom; Not yet recruiting
Christopher Imray, Principal Investigator

St Mary's Hospital, Imperial College Healthcare NHS Trust, London W21PG, United Kingdom; Recruiting
Colin Bicknell, Principal Investigator

Charing Cross Hospital, Imperial College NHS Trust, London W6 8RF, United Kingdom; Not yet recruiting
Janet Powell, Principal Investigator

St Thomas' Hospital, London SE1 7EH, United Kingdom; Not yet recruiting
Matthew Waltham, Principal Investigator

Royal Free Hospital, London NW3 2QG, United Kingdom; Not yet recruiting
Meryl Davis, Principal Investigator

Starting date: September 2011
Last updated: October 4, 2011