AARDVARK (Aortic Aneurysmal Regression of Dilation: Value of ACE-Inhibition on RisK)

Abdominal Aortic Aneurysm Clinical Trial

— AARDVARK  

Official title:

An Evaluation of the Effect of an Angiotensin-converting Enzyme (ACE) Inhibitor on the Growth Rate of Small Abdominal Aortic Aneurysms.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01118520
• Other study ID #: CRO1644
• Secondary ID: 2010-020226-1708
• Status: Completed
• Phase: Phase 2
• Start date: September 2011
• Est. completion date: April 2015

Study information

• Verified date: January 2021
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 224
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Abdominal Aortic Aneurysm
• Aneurysm
• Aortic Aneurysm
• Aortic Aneurysm, Abdominal

Intervention

Drug:
• perindopril arginine
10mgs orally daily for the duration of the trial
• amlodipine 5mgs
5 mgs taken orally daily for the duration of the trial
• placebo
one daily

Locations

Country	Name	City	State
United Kingdom	The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust	Bournemouth
United Kingdom	Colchester Hospital	Colchester
United Kingdom	University Hospital Coventry and Warwickshire	Coventry
United Kingdom	Hull Royal Infirmary	Hull
United Kingdom	Charing Cross Hospital, Imperial College NHS Trust	London
United Kingdom	Royal Free Hospital	London
United Kingdom	St Mary's Hospital, Imperial College Healthcare NHS Trust	London
United Kingdom	St Thomas' Hospital	London
United Kingdom	Freeman Hospital	Newcastle

Sponsors (2)

Lead Sponsor	Collaborator
Imperial College London	National Institute for Health Research, United Kingdom

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the Growth Rate of Abdominal Aortic Aneurysm	Aneurysm growth rate over 2 years, estimated from the sequential AAA diameter measurements (external diameter measured in the longitudinal plane).	Annual rate over the entire period of 24 month
Secondary	Number of Participants With Aneurysm Related Death		24 months

External Links

•   AARDVARK Publication