Evaluation of Effect of Angiotensin-converting Enzyme (ACE) Inhibitors on Small Aneurysm Growth Rate (AARDVARK)
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Abdominal Aortic Aneurysm |
Drug: perindopril arginine Drug: amlodipine 5mgs Drug: placebo |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment |
| 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 |
- reduction growth rate of abdominal aortic aneurysm [ Time Frame: every three months ] [ Designated as safety issue: Yes ]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.
- effect of treatment with perindopril on aneurysm related death rates [ Time Frame: 42 months ] [ Designated as safety issue: Yes ]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.
| Estimated Enrollment: | 225 |
| Study Start Date: | September 2011 |
| Estimated Study Completion Date: | October 2014 |
| Estimated Primary Completion Date: | August 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: perindopril
ACE inhibitor blood pressure lowering agent
|
Drug: perindopril arginine
10mgs orally daily for the duration of the trial
Other Name: 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
|
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.
Eligibility| Ages Eligible for Study: | 60 Years to 85 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations| Contact: Neil R Poulter, FRCP | 02075943446 | n.poulter@imperial.ac.uk |
| Contact: Simon A Whitehouse, MB BS | 02075943413 | a.whitehouse@imperial.ac.uk |
| United Kingdom | |
| University Hospital Coventry and Warwickshire | Not yet recruiting |
| Coventry, United Kingdom, CV2 2DX | |
| Principal Investigator: Christopher Imray | |
| St Mary's Hospital, Imperial College Healthcare NHS Trust | Recruiting |
| London, United Kingdom, W21PG | |
| Principal Investigator: Colin Bicknell | |
| Charing Cross Hospital, Imperial College NHS Trust | Not yet recruiting |
| London, United Kingdom, W6 8RF | |
| Principal Investigator: Janet Powell | |
| St Thomas' Hospital | Not yet recruiting |
| London, United Kingdom, SE1 7EH | |
| Principal Investigator: Matthew Waltham | |
| Royal Free Hospital | Not yet recruiting |
| London, United Kingdom, NW3 2QG | |
| Principal Investigator: Meryl Davis | |
| Principal Investigator: | Janet Powell, MD | Imperial College Charing Cross |
| Principal Investigator: | Colin Bucknell, MD | Imperial Colege St Marys |
| Study Director: | deborah Ashby, PhD | Imperial college. Faculty of Medicine statistics |
| Principal Investigator: | Meryl E davis, FRCS | Royal Free Hospital NHS Trust |
| Principal Investigator: | Mathew M Thompson, MD | St Georges Hospital Medical School |
| Principal Investigator: | Mathew Waltham | Guys Hospital NHS trust |
More Information
No publications provided
| Responsible Party: | Imperial College London |
| ClinicalTrials.gov Identifier: | NCT01118520 History of Changes |
| Other Study ID Numbers: | CRO1644, 2010-020226-17, 08/109/02 |
| Study First Received: | May 5, 2010 |
| Last Updated: | October 4, 2011 |
| Health Authority: | United Kingdom: Medicines and Healthcare Products Regulatory Agency United Kingdom: National Health Service United Kingdom: National Institute for Health Research United Kingdom: Research Ethics Committee |
Keywords provided by Imperial College London:
|
abdominal aortic aneurysm ACE Inhibition |
Additional relevant MeSH terms:
|
Aneurysm Aortic Aneurysm Aortic Aneurysm, Abdominal Vascular Diseases Cardiovascular Diseases Aortic Diseases Angiotensin-Converting Enzyme Inhibitors Perindopril Amlodipine Protease Inhibitors |
Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Calcium Channel Blockers Membrane Transport Modulators Cardiovascular Agents Therapeutic Uses Vasodilator Agents Antihypertensive Agents |
ClinicalTrials.gov processed this record on May 23, 2013