Clinical trial NCT01118520: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Abdominal Aortic Aneurysm
Keywords: abdominal aortic aneurysm
ACE Inhibition
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
First posted: 2010-05-06
Enrollment: 224
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in the Growth Rate of Abdominal Aortic Aneurysm
timeFrame: Annual rate over the entire period of 24 month
Secondary outcomes:
measure: Number of Participants With Aneurysm Related Death
timeFrame: 24 months
Other outcomes:
Locations:
city: Bournemouth
country: United Kingdom
facility: The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust
city: Colchester
country: United Kingdom
facility: Colchester Hospital
city: Coventry
country: United Kingdom
facility: University Hospital Coventry and Warwickshire
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: St Thomas' Hospital
city: London
country: United Kingdom
facility: St Mary's Hospital, Imperial College Healthcare NHS Trust
city: London
country: United Kingdom
facility: Charing Cross Hospital, Imperial College NHS Trust
city: Newcastle
country: United Kingdom
facility: Freeman Hospital
Study officials:
affiliation: Imperial College London
name: Janet Powell, MD
role: STUDY_DIRECTOR
affiliation: Imperial College London
name: Colin Bicknell, FRCS
role: STUDY_DIRECTOR
affiliation: Imperial College London
name: Deborah Ashby, PhD
role: STUDY_DIRECTOR
affiliation: Royal Free Hospital NHS Trust
name: Meryl E Davis, FRCS
role: PRINCIPAL_INVESTIGATOR
affiliation: Guys Hospital NHS trust
name: Mathew Waltham, FRCS
role: PRINCIPAL_INVESTIGATOR
affiliation: Imperial College London
name: Neil Poulter, FRCP
role: STUDY_DIRECTOR
affiliation: University Hospitals Coventry & Warwickshire
name: Christopher Imray, FRCS
role: PRINCIPAL_INVESTIGATOR
affiliation: The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust
name: Dynesh Rittoo, FRCS
role: PRINCIPAL_INVESTIGATOR
affiliation: Hull University Teaching Hospitals NHS Trust
name: Ian Chetter, FRCS
role: PRINCIPAL_INVESTIGATOR
affiliation: East Suffolk and North Essex NHS Foundation Trust
name: Sohail Choksy, FRCS
role: PRINCIPAL_INVESTIGATOR
affiliation: The Newcastle Hospitals NHS Foundation Trust
name: Tim Lees, FRCS
role: PRINCIPAL_INVESTIGATOR
affiliation: York Teaching Hospital NHS Foundation Trust
name: Andrew Thompson, FRCS
role: PRINCIPAL_INVESTIGATOR
affiliation: Manchester University NHS Foundation Trust
name: Vince Smyth, FRCS
role: PRINCIPAL_INVESTIGATOR
affiliation: Sheffield Teaching Hospitals NHS Foundation Trust
name: Shah Nawaz, FRCS
role: PRINCIPAL_INVESTIGATOR
affiliation: City Hospitals Sunderland NHS Foundation Trust
name: Andrew Brown, FRCS
role: PRINCIPAL_INVESTIGATOR
affiliation: Norfolk and Norwich University Hospitals NHS Foundation Trust
name: Felicity Meyer, FRCS
role: PRINCIPAL_INVESTIGATOR
References: