Clinical trial NCT01118520
Conditions: Abdominal Aortic Aneurysm
Keywords: abdominal aortic aneurysm ACE Inhibition
Sponsor: Imperial College London
Start date: 2011-09-01; Completion date: 2015-04-01
Enrollment: 224 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: ACE inhibitor blood pressure lowering agent arm 2: calcium channel blocker blood pressure lowering agent arm 3: inactive substance identical in appearance to the othe two comparators
Interventions: intervention 1: perindopril arginine intervention 2: amlodipine 5mgs intervention 3: placebo
Intervention descriptions: intervention 1: 10mgs orally daily for the duration of the trial intervention 2: 5 mgs taken orally daily for the duration of the trial intervention 3: one daily

Protocol documents:
Prot_000.pdf: 
AARDVARK 
Short summary 
final version 1
 
 
29/07/2010 
Title: An evaluation of the effect of an angiotensin-converting enzyme 
(ACE) inhibitor on the growth rate of small abdominal aortic aneurysms 
 
AARDVARK Aortic Aneurysmal Regression of Dilation : Value of Ace-inhibition on Ris K  
 
Objectives:  
1.  To investigate the hypothesis that an ACE-inhibitor reduces abdominal aortic aneurysm 
(AAA) growth rate. In a pilot 3-arm randomised controlled trial: The three interventions are 
ACE-inhibition with perindopril versus equivalent blood pressure reduction with amlodipine (a 
calcium channel blocker) versus placebo. By comparing the effects in the perindopril and 
amlodipine arms, this design will permit an evaluation of any blood pressure independent 
effects of perindopril. 
2.  Pending results of the pilot trial, to work with the local and National Aneurysm Screening 
programme to conduct a larger, definitive 3-arm randomised controlled 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.  Aneurysm-related 
mortality, morbidity and quality of life will be the major secondary end-points. 
 
The pilot trial will recruit approximately 225 patients from aortic aneurysm screening sites in 
or near to London.  They will be seen and assessed with an ultrasound examination every 
three months for a period of 24 months. 
 
(i) 
Inclusion criteria 
(ii) 
All men or women, aged OVER 60 years, with AAA between 3.0 and 5.5 cm and 
with a systolic BP <150mmHg will be eligible for inclusion in the trial unless they 
are routinely already receiving an ACE-inhibitor or amlodipine 10mg daily. For 
patients whose systolic BP is >150mmHg, a 6 week course of the diuretic 
indapamide SR (1.5mg daily) will be given, with re-evaluation of  BP in the 6th 
week:  If the SBP falls to <150mmHg on this medication subjects would then be 
eligible for inclusion into the study. If this diuretic treatment is not appropriate 
then 5mgs of amlodipine could be prescribed by the patients GP if not already 
taking this drug.  This would be followed by a six week re-evaluation as above. 
. 
(ii) 
Exclusion criteria  
 
1. 
Patients who cannot be converted to diuretic therapy and/or lower doses of amlodipine 
or patients already taking an angiotensin II antagonist (ARB) for the treatment of blood 
pressue. 
2. 
those with known renal artery stenosis (>50%), or with a serum creatinine > 180umol/L 
on routine testing. 
3. 
those unable to give informed consent   
4. 
those too frail to travel for 3-monthly surveillance will be excluded. 
5. 
Any clinically significant medical condition which, in the opinion of the investigator, 
may interfere with the study results; 
6. 
Participation in another trial of an investigational product or device within the previous 
30 days; 
7. 
Known allergy or sensitivity to perindopril or amlodipine 
8. 
Unable or unwilling to comply with the requirements of the study, in the opinion of the 
investigator. 
 


AARDVARK 
Short summary 
final version 1
 
 
29/07/2010 
 
Project Timetable and Milestones 
 
   Set up  
 
Recruitment 
 
         =24 months   
      
Close out 
┴────────┴─────────────┴──────────────────┴────────┴ 
 0 
 
6 
 
 
18 
 
 
 
36 
 
42 
 
 
 
Total trial length = 42 months. 
 
 
 
 
 
Local sceening  
centre staff   
Screen & 
Consent 
Project co-
ordinator 
And medical 
investigator 
 
Randomisation 
Project co-ordinator 
 
Treatment 
Project co-ordinator 
 
 
 
Visit  
-2 
Suitable 
patients 
identified and 
contacted 
-1 
 
AAA 3.0-5.4cm? 
SBP<150mmHg
? 
 
1 
(Baseline) 
Either 1 week after blood 
test or 6 weeks after starting 
indapamide 
2 
3 
4 
5 
6 
7 
8 
9 
Months 
 
-2 to 0.25 
0 
3 
6 
9 
12 
15 
18 
21 
24 
Inclusion & 
exclusion 
criteria  
 
X 
check 
 
 
 
 
 
 
 
 
 Informed 
consent 
 
X 
check 
 
 
 
 
 
 
 
 
Demography 
 
X 
 
 
 
 
 
 
 
 
 
Past medical 
history  
 
X 
 
 
 
 
 
 
 
 
 
Current medical 
therapies 
 
X 
check 
X 
X 
X 
X 
X 
X 
X 
X 
Ultrasound of 
AAA 
AAA 3.0-5.4cm? 
 
review 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Blood pressure 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Pill count 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Blood for 
creatinine and 
electrolytes 
 
X 
review 
X 
 
 
X 
 
 
 
X 
Blood for lipid 
profile 
 
X 
review 
check lipid lowing 
prescribed 
 
 
 
 
 
 
 
 
 
EuroQoL, health 
resource 
questionnaire 
 
 
 
 
 
 
X 
 
 
 
X 
Time  
(months) 
          ↑ 
Start of trial 
          ↑ 
End of trial