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

Sponsor
Imperial College London (Other)
Overall Status
Completed
CT.gov ID
NCT01118520
Collaborator
National Institute for Health Research, United Kingdom (Other)
224
Enrollment
9
Locations
3
Arms
43
Actual Duration (Months)
24.9
Patients Per Site
0.6
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: perindopril arginine
  • Drug: amlodipine 5mgs
  • Drug: placebo
 Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
224 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, 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.
Actual Study Start Date :
Sep 1, 2011
Actual Primary Completion Date :
Apr 1, 2015
Actual Study Completion Date :
Apr 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: perindopril

ACE inhibitor blood pressure lowering agent

Drug: perindopril arginine
10mgs orally daily for the duration of the trial
Other Names:
  • 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

    Outcome Measures

    Primary Outcome Measures

    1. Change in the Growth Rate of Abdominal Aortic Aneurysm [Annual rate over the entire period of 24 month]

      Aneurysm growth rate over 2 years, estimated from the sequential AAA diameter measurements (external diameter measured in the longitudinal plane).

    Secondary Outcome Measures

    1. Number of Participants With Aneurysm Related Death [24 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    55 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust Bournemouth United Kingdom BH7 7DW
    2 Colchester Hospital Colchester United Kingdom CO4 5JL
    3 University Hospital Coventry and Warwickshire Coventry United Kingdom CV2 2DX
    4 Hull Royal Infirmary Hull United Kingdom HU3 2JZ
    5 Royal Free Hospital London United Kingdom NW3 2QG
    6 St Thomas' Hospital London United Kingdom SE1 7EH
    7 St Mary's Hospital, Imperial College Healthcare NHS Trust London United Kingdom W21PG
    8 Charing Cross Hospital, Imperial College NHS Trust London United Kingdom W6 8RF
    9 Freeman Hospital Newcastle United Kingdom NE7 7DN

    Sponsors and Collaborators

    • Imperial College London
    • National Institute for Health Research, United Kingdom

    Investigators

    • Study Director: Janet Powell, MD, Imperial College London
    • Study Director: Colin Bicknell, FRCS, Imperial College London
    • Study Director: Deborah Ashby, PhD, Imperial College London
    • Principal Investigator: Meryl E Davis, FRCS, Royal Free Hospital NHS Trust
    • Principal Investigator: Mathew Waltham, FRCS, Guys Hospital NHS trust
    • Study Director: Neil Poulter, FRCP, Imperial College London
    • Principal Investigator: Christopher Imray, FRCS, University Hospitals Coventry & Warwickshire
    • Principal Investigator: Dynesh Rittoo, FRCS, The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust
    • Principal Investigator: Ian Chetter, FRCS, Hull University Teaching Hospitals NHS Trust
    • Principal Investigator: Sohail Choksy, FRCS, East Suffolk and North Essex NHS Foundation Trust
    • Principal Investigator: Tim Lees, FRCS, The Newcastle Hospitals NHS Foundation Trust
    • Principal Investigator: Andrew Thompson, FRCS, York Teaching Hospital NHS Foundation Trust
    • Principal Investigator: Vince Smyth, FRCS, Manchester University NHS Foundation Trust
    • Principal Investigator: Shah Nawaz, FRCS, Sheffield Teaching Hospitals NHS Foundation Trust
    • Principal Investigator: Andrew Brown, FRCS, City Hospitals Sunderland NHS Foundation Trust
    • Principal Investigator: Felicity Meyer, FRCS, Norfolk and Norwich University Hospitals NHS Foundation Trust

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Imperial College London
    ClinicalTrials.gov Identifier:
    NCT01118520
    Other Study ID Numbers:
    • CRO1644
    • 2010-020226-17
    • 08/109/02
    First Posted:
    May 6, 2010
    Last Update Posted:
    Jan 26, 2021
    Last Verified:
    Jan 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Imperial College London
    abdominal aortic aneurysm
    ACE Inhibition
    Additional relevant MeSH terms:
    Aneurysm
    Aortic Aneurysm
    Aortic Aneurysm, Abdominal
    Amlodipine
    Perindopril

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Perindopril Amlodipine Placebo
    Arm/Group Description 10mgs orally daily for the duration of the trial 5 mgs taken orally daily for the duration of the trial one daily
    Period Title: Overall Study
    STARTED 73 72 79
    COMPLETED 53 49 59
    NOT COMPLETED 20 23 20

    Baseline Characteristics

    Arm/Group Title Perindopril Amlodipine Placebo Total
    Arm/Group Description 10mgs orally daily for the duration of the trial 5 mgs taken orally daily for the duration of the trial one daily Total of all reporting groups
    Overall Participants 73 72 79 224
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    71.6
    (6.9)
    71.5
    (6.7)
    70.7
    (7.5)
    71.2
    (7.1)
    Sex: Female, Male (Count of Participants)
    Female
    2
    2.7%
    6
    8.3%
    5
    6.3%
    13
    5.8%
    Male
    71
    97.3%
    66
    91.7%
    74
    93.7%
    211
    94.2%
    Race and Ethnicity Not Collected (Count of Participants)
    Count of Participants [Participants]
    0
    0%
    Region of Enrollment (participants) [Number]
    United Kingdom
    73
    100%
    72
    100%
    79
    100%
    224
    100%
    Number of participants receiving statin treatment (Count of Participants)
    Count of Participants [Participants]
    53
    72.6%
    45
    62.5%
    48
    60.8%
    146
    65.2%
    Number of participants with diabetes (Count of Participants)
    Count of Participants [Participants]
    2
    2.7%
    6
    8.3%
    8
    10.1%
    16
    7.1%
    Systolic blood pressure (mmHg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHg]
    130.9
    (11.5)
    131.9
    (13)
    131.7
    (12.2)
    131.5
    (12.2)
    Diastolic blood pressure (mmHg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHg]
    76.7
    (8)
    78.7
    (7)
    77.9
    (7.6)
    77.7
    (7.5)
    Abdominal Aortic Aneurysm external longitudinal diameter (cm) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [cm]
    4.05
    (0.65)
    4.03
    (0.69)
    4.06
    (0.67)
    4.05
    (0.67)

    Outcome Measures

    1. Primary Outcome
    Title Change in the Growth Rate of Abdominal Aortic Aneurysm
    Description Aneurysm growth rate over 2 years, estimated from the sequential AAA diameter measurements (external diameter measured in the longitudinal plane).
    Time Frame Annual rate over the entire period of 24 month

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Perindopril Amlodipine Placebo
    Arm/Group Description 10mgs orally daily for the duration of the trial 5 mgs taken orally daily for the duration of the trial one daily
    Measure Participants 73 72 79
    Least Squares Mean (Standard Error) [mm]
    1.77
    (0.02)
    1.81
    (0.02)
    1.66
    (0.02)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Perindopril, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.78
    Comments
    Method Mixed Models Analysis
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Perindopril, Amlodipine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.89
    Comments
    Method Mixed Models Analysis
    Comments
    2. Secondary Outcome
    Title Number of Participants With Aneurysm Related Death
    Description
    Time Frame 24 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Perindopril Amlodipine Placebo
    Arm/Group Description 10mgs orally daily for the duration of the trial 5 mgs taken orally daily for the duration of the trial one daily
    Measure Participants 73 72 79
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%

    Adverse Events

    Time Frame 24 months
    Adverse Event Reporting Description
    Arm/Group Title Perindopril Amlodipine Placebo
    Arm/Group Description 10mgs orally daily for the duration of the trial 5 mgs taken orally daily for the duration of the trial one daily
    All Cause Mortality
    Perindopril Amlodipine Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/73 (2.7%) 2/72 (2.8%) 3/79 (3.8%)
    Serious Adverse Events
    Perindopril Amlodipine Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 19/73 (26%) 12/72 (16.7%) 16/79 (20.3%)
    Blood and lymphatic system disorders
    Neutropenia 0/73 (0%) 0 0/72 (0%) 0 1/79 (1.3%) 1
    Cardiac disorders
    Myocardial infarction 0/73 (0%) 0 0/72 (0%) 0 1/79 (1.3%) 1
    Pericarditis 0/73 (0%) 0 0/72 (0%) 0 1/79 (1.3%) 1
    Atrial flutter 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Heart block 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Chest pain 1/73 (1.4%) 1 0/72 (0%) 0 2/79 (2.5%) 2
    Stroke 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Eye disorders
    Cataract surgery 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Visual field defect 0/73 (0%) 0 1/72 (1.4%) 1 0/79 (0%) 0
    Gastrointestinal disorders
    Melaena 0/73 (0%) 0 0/72 (0%) 0 1/79 (1.3%) 1
    Abdominal pain 2/73 (2.7%) 2 1/72 (1.4%) 1 1/79 (1.3%) 1
    Gastrointestinal bleed 0/73 (0%) 0 2/72 (2.8%) 2 1/79 (1.3%) 1
    Rectal bleeding 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Vomiting 2/73 (2.7%) 2 0/72 (0%) 0 0/79 (0%) 0
    General disorders
    Rectum biopsy 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Swelling of legs 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Hepatobiliary disorders
    Gallstones 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Gallbladder perforation 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Obstructive jaundice 0/73 (0%) 0 0/72 (0%) 0 1/79 (1.3%) 1
    Hepatic disease 0/73 (0%) 0 1/72 (1.4%) 1 0/79 (0%) 0
    Infections and infestations
    Chest infection 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Urinary infection 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Cellulitis of leg 0/73 (0%) 0 0/72 (0%) 0 1/79 (1.3%) 1
    Cellulitis of arm 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Injury, poisoning and procedural complications
    Fracture neck of femur 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Fall 1/73 (1.4%) 2 0/72 (0%) 0 0/79 (0%) 0
    Bladder injury 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Compression fracture 0/73 (0%) 0 1/72 (1.4%) 1 0/79 (0%) 0
    Investigations
    Angiography 0/73 (0%) 0 1/72 (1.4%) 1 1/79 (1.3%) 1
    Laryngoscopy 0/73 (0%) 0 0/72 (0%) 0 1/79 (1.3%) 1
    Cytoscopy 0/73 (0%) 0 0/72 (0%) 0 1/79 (1.3%) 1
    Endoscopy 0/73 (0%) 0 1/72 (1.4%) 1 0/79 (0%) 0
    Angiogram 0/73 (0%) 0 1/72 (1.4%) 1 0/79 (0%) 0
    Musculoskeletal and connective tissue disorders
    Back pain 0/73 (0%) 0 1/72 (1.4%) 1 0/79 (0%) 0
    Ankle swelling 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lunger cancer metastatic 2/73 (2.7%) 2 1/72 (1.4%) 1 0/79 (0%) 0
    Adenocarcinoma of prostate 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    COPD exacerbation 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Shortness of breath 0/73 (0%) 0 0/72 (0%) 0 2/79 (2.5%) 2
    Haemoptysis 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Surgical and medical procedures
    Spinal decomperession 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Inguinal hernia repair 1/73 (1.4%) 1 0/72 (0%) 0 1/79 (1.3%) 1
    Toe operation 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Aortic aneurysm repair 0/73 (0%) 0 1/72 (1.4%) 1 1/79 (1.3%) 1
    Aneurysm embolism 0/73 (0%) 0 0/72 (0%) 0 1/79 (1.3%) 1
    Prostatectomy 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Prostate transurethal resection 0/73 (0%) 0 1/72 (1.4%) 1 0/79 (0%) 0
    Surgery 0/73 (0%) 0 0/72 (0%) 0 1/79 (1.3%) 1
    Bowel resection 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Biopsy penis 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Laser prostatectomy 0/73 (0%) 0 1/72 (1.4%) 1 0/79 (0%) 0
    Appendictomy 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Angioplasty 0/73 (0%) 0 1/72 (1.4%) 1 0/79 (0%) 0
    Vascular disorders
    Pulmonary embolism 0/73 (0%) 0 1/72 (1.4%) 1 1/79 (1.3%) 1
    Angiodisplasia 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Hypertension 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Deep vein thrombosis 0/73 (0%) 0 1/72 (1.4%) 1 0/79 (0%) 0
    Collapse 0/73 (0%) 0 0/72 (0%) 0 1/79 (1.3%) 1
    Other (Not Including Serious) Adverse Events
    Perindopril Amlodipine Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/73 (9.6%) 8/72 (11.1%) 9/79 (11.4%)
    Cardiac disorders
    Heart failure 0/73 (0%) 0 1/72 (1.4%) 1 0/79 (0%) 0
    Gastrointestinal disorders
    Upset stomach 0/73 (0%) 0 0/72 (0%) 0 1/79 (1.3%) 1
    Abdominal pain 0/73 (0%) 0 0/72 (0%) 0 1/79 (1.3%) 1
    Hiatus hernia 0/73 (0%) 0 0/72 (0%) 0 1/79 (1.3%) 1
    General disorders
    Numbness in hands, forearms, elbows 0/73 (0%) 0 0/72 (0%) 0 1/79 (1.3%) 1
    Sweating 0/73 (0%) 0 0/72 (0%) 0 1/79 (1.3%) 1
    Feeling sick 0/73 (0%) 0 0/72 (0%) 0 1/79 (1.3%) 1
    Feeling unwell 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Other 0/73 (0%) 0 0/72 (0%) 0 1/79 (1.3%) 1
    Metabolism and nutrition disorders
    Type 2 diabetes mellitus 0/73 (0%) 0 0/72 (0%) 0 1/79 (1.3%) 1
    Musculoskeletal and connective tissue disorders
    Ankle swelling 0/73 (0%) 0 3/72 (4.2%) 3 0/79 (0%) 0
    Nervous system disorders
    Diziness 3/73 (4.1%) 3 1/72 (1.4%) 1 0/79 (0%) 0
    Headache 0/73 (0%) 0 1/72 (1.4%) 1 0/79 (0%) 0
    Blackout 0/73 (0%) 0 1/72 (1.4%) 1 0/79 (0%) 0
    Numbness in feet 0/73 (0%) 0 0/72 (0%) 0 1/79 (1.3%) 1
    Respiratory, thoracic and mediastinal disorders
    Breathlessness 0/73 (0%) 0 1/72 (1.4%) 1 0/79 (0%) 0
    Cough 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Skin and subcutaneous tissue disorders
    Itchy skin 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0
    Vascular disorders
    Hypotension 1/73 (1.4%) 1 0/72 (0%) 0 0/79 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Professor Neil Poulter
    Organization Imperial College London
    Phone +44(0) 20 7594 3446
    Email n.poulter@imperial.ac.uk
    Responsible Party:
    Imperial College London
    ClinicalTrials.gov Identifier:
    NCT01118520
    Other Study ID Numbers:
    • CRO1644
    • 2010-020226-17
    • 08/109/02
    First Posted:
    May 6, 2010
    Last Update Posted:
    Jan 26, 2021
    Last Verified:
    Jan 1, 2021