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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2011 by Imperial College London.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
Imperial College London
ClinicalTrials.gov Identifier:
NCT01118520
First received: May 5, 2010
Last updated: October 4, 2011
Last verified: October 2011
  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

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01118520

Contacts
Contact: Neil R Poulter, FRCP 02075943446 n.poulter@imperial.ac.uk
Contact: Simon A Whitehouse, MB BS 02075943413 a.whitehouse@imperial.ac.uk

Locations
United Kingdom
University Hospital Coventry and Warwickshire Not yet recruiting
Coventry, United Kingdom, CV2 2DX
Principal Investigator: Christopher Imray         
Charing Cross Hospital, Imperial College NHS Trust Not yet recruiting
London, United Kingdom, W6 8RF
Principal Investigator: Janet Powell         
Royal Free Hospital Not yet recruiting
London, United Kingdom, NW3 2QG
Principal Investigator: Meryl Davis         
St Mary's Hospital, Imperial College Healthcare NHS Trust Recruiting
London, United Kingdom, W21PG
Principal Investigator: Colin Bicknell         
St Thomas' Hospital Not yet recruiting
London, United Kingdom, SE1 7EH
Principal Investigator: Matthew Waltham         
Sponsors and Collaborators
Imperial College London
National Institute for Health Research, United Kingdom
Investigators
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
Aortic Diseases
Cardiovascular Diseases
Vascular Diseases
Amlodipine
Angiotensin-Converting Enzyme Inhibitors
Perindopril
Antihypertensive Agents
Calcium Channel Blockers
Cardiovascular Agents
Enzyme Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on October 22, 2014