Abdominal Aortic Aneurysm
Conditions
Keywords
abdominal aortic aneurysm, ACE Inhibition
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.
Interventions
10mgs orally daily for the duration of the trial
DRUGamlodipine 5mgs
5 mgs taken orally daily for the duration of the trial
DRUGplacebo
one daily
Sponsors
National Institute for Health Research, United Kingdom
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| Number of Participants With Aneurysm Related Death | 24 months |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Perindopril 10mgs orally daily for the duration of the trial | 73 |
| Amlodipine 5 mgs taken orally daily for the duration of the trial | 72 |
| Placebo one daily | 79 |
| Total | 224 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | AAA repair | 9 | 7 | 9 |
| Overall Study | Adverse Event | 3 | 3 | 3 |
| Overall Study | Withdrawal by Subject | 8 | 13 | 8 |
Baseline characteristics
| Characteristic | Perindopril | Total | Placebo | Amlodipine |
|---|---|---|---|---|
| Abdominal Aortic Aneurysm external longitudinal diameter | 4.05 cm STANDARD_DEVIATION 0.65 | 4.05 cm STANDARD_DEVIATION 0.67 | 4.06 cm STANDARD_DEVIATION 0.67 | 4.03 cm STANDARD_DEVIATION 0.69 |
| Age, Continuous | 71.6 years STANDARD_DEVIATION 6.9 | 71.2 years STANDARD_DEVIATION 7.1 | 70.7 years STANDARD_DEVIATION 7.5 | 71.5 years STANDARD_DEVIATION 6.7 |
| Diastolic blood pressure | 76.7 mmHg STANDARD_DEVIATION 8 | 77.7 mmHg STANDARD_DEVIATION 7.5 | 77.9 mmHg STANDARD_DEVIATION 7.6 | 78.7 mmHg STANDARD_DEVIATION 7 |
| Number of participants receiving statin treatment | 53 Participants | 146 Participants | 48 Participants | 45 Participants |
| Number of participants with diabetes | 2 Participants | 16 Participants | 8 Participants | 6 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — | — |
| Region of Enrollment United Kingdom | 73 participants | 224 participants | 79 participants | 72 participants |
| Sex: Female, Male Female | 2 Participants | 13 Participants | 5 Participants | 6 Participants |
| Sex: Female, Male Male | 71 Participants | 211 Participants | 74 Participants | 66 Participants |
| Systolic blood pressure | 130.9 mmHg STANDARD_DEVIATION 11.5 | 131.5 mmHg STANDARD_DEVIATION 12.2 | 131.7 mmHg STANDARD_DEVIATION 12.2 | 131.9 mmHg STANDARD_DEVIATION 13 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 73 | 2 / 72 | 3 / 79 |
| other Total, other adverse events | 7 / 73 | 8 / 72 | 9 / 79 |
| serious Total, serious adverse events | 19 / 73 | 12 / 72 | 16 / 79 |
Outcome results
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).
Time frame: Annual rate over the entire period of 24 month
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Perindopril | Change in the Growth Rate of Abdominal Aortic Aneurysm | 1.77 mm | Standard Error 0.02 |
| Amlodipine | Change in the Growth Rate of Abdominal Aortic Aneurysm | 1.81 mm | Standard Error 0.02 |
| Placebo | Change in the Growth Rate of Abdominal Aortic Aneurysm | 1.66 mm | Standard Error 0.02 |
p-value: 0.78Mixed Models Analysis
p-value: 0.89Mixed Models Analysis
Secondary
Number of Participants With Aneurysm Related Death
Time frame: 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Perindopril | Number of Participants With Aneurysm Related Death | 0 Participants |
| Amlodipine | Number of Participants With Aneurysm Related Death | 0 Participants |
| Placebo | Number of Participants With Aneurysm Related Death | 0 Participants |