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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-020226-17 | EudraCT Number | ||
| 08/109/02 | Other Grant/Funding Number | NIHR |
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| Name | Class |
|---|---|
| National Institute for Health Research, United Kingdom | OTHER_GOV |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| perindopril | Active Comparator | ACE inhibitor blood pressure lowering agent |
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| amlodipine | Active Comparator | calcium channel blocker blood pressure lowering agent |
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| placebo | Placebo Comparator | inactive substance identical in appearance to the othe two comparators |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| perindopril arginine | Drug | 10mgs orally daily for the duration of the trial |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Aneurysm Related Death | 24 months |
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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.
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| Name | Affiliation | Role |
|---|---|---|
| Janet Powell, MD | Imperial College London | Study Director |
| Colin Bicknell, FRCS | Imperial College London | Study Director |
| Deborah Ashby, PhD | Imperial College London | Study Director |
| Meryl E Davis, FRCS | Royal Free Hospital NHS Trust | Principal Investigator |
| Mathew Waltham, FRCS | Guys Hospital NHS trust | Principal Investigator |
| Neil Poulter, FRCP | Imperial College London | Study Director |
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust | Bournemouth | BH7 7DW | United Kingdom | |||
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| ID | Title | Description |
|---|---|---|
| FG000 | Perindopril | 10mgs orally daily for the duration of the trial |
| FG001 | Amlodipine | 5 mgs taken orally daily for the duration of the trial |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 29, 2010 | May 8, 2019 |
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| amlodipine 5mgs | Drug | 5 mgs taken orally daily for the duration of the trial |
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| placebo | Drug | one daily |
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| 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 | Principal Investigator |
| Colchester Hospital |
| Colchester |
| CO4 5JL |
| United Kingdom |
| University Hospital Coventry and Warwickshire | Coventry | CV2 2DX | United Kingdom |
| Hull Royal Infirmary | Hull | HU3 2JZ | United Kingdom |
| Royal Free Hospital | London | NW3 2QG | United Kingdom |
| St Thomas' Hospital | London | SE1 7EH | United Kingdom |
| St Mary's Hospital, Imperial College Healthcare NHS Trust | London | W21PG | United Kingdom |
| Charing Cross Hospital, Imperial College NHS Trust | London | W6 8RF | United Kingdom |
| Freeman Hospital | Newcastle | NE7 7DN | United Kingdom |
| FG002 | Placebo | one daily |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Perindopril | 10mgs orally daily for the duration of the trial |
| BG001 | Amlodipine | 5 mgs taken orally daily for the duration of the trial |
| BG002 | Placebo | one daily |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Number of participants receiving statin treatment | Count of Participants | Participants |
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| Number of participants with diabetes | Count of Participants | Participants |
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| Systolic blood pressure | Mean | Standard Deviation | mmHg |
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| Diastolic blood pressure | Mean | Standard Deviation | mmHg |
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| Abdominal Aortic Aneurysm external longitudinal diameter | Mean | Standard Deviation | cm |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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). | Posted | Least Squares Mean | Standard Error | mm | Annual rate over the entire period of 24 month |
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| Secondary | Number of Participants With Aneurysm Related Death | Posted | Count of Participants | Participants | 24 months |
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24 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Perindopril | 10mgs orally daily for the duration of the trial | 2 | 73 | 19 | 73 | 7 | 73 |
| EG001 | Amlodipine | 5 mgs taken orally daily for the duration of the trial | 2 | 72 | 12 | 72 | 8 | 72 |
| EG002 | Placebo | one daily | 3 | 79 | 16 | 79 | 9 | 79 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pulmonary embolism | Vascular disorders | MedDRA (10.0) | Systematic Assessment |
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| Angiodisplasia | Vascular disorders | MedDRA (10.0) | Systematic Assessment |
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| Rectum biopsy | General disorders | MedDRA (10.0) | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA (10.0) | Systematic Assessment |
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| Deep vein thrombosis | Vascular disorders | MedDRA (10.0) | Systematic Assessment |
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| Collapse | Vascular disorders | MedDRA (10.0) | Systematic Assessment |
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| Spinal decomperession | Surgical and medical procedures | MedDRA (10.0) | Systematic Assessment |
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| Inguinal hernia repair | Surgical and medical procedures | MedDRA (10.0) | Systematic Assessment |
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| Toe operation | Surgical and medical procedures | MedDRA (10.0) | Systematic Assessment |
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| Aortic aneurysm repair | Surgical and medical procedures | MedDRA (10.0) | Systematic Assessment |
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| Aneurysm embolism | Surgical and medical procedures | MedDRA (10.0) | Systematic Assessment |
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| Prostatectomy | Surgical and medical procedures | MedDRA (10.0) | Systematic Assessment |
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| Prostate transurethal resection | Surgical and medical procedures | MedDRA (10.0) | Systematic Assessment |
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| Surgery | Surgical and medical procedures | MedDRA (10.0) | Systematic Assessment |
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| Bowel resection | Surgical and medical procedures | MedDRA (10.0) | Systematic Assessment |
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| Biopsy penis | Surgical and medical procedures | MedDRA (10.0) | Systematic Assessment |
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| Laser prostatectomy | Surgical and medical procedures | MedDRA (10.0) | Systematic Assessment |
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| Appendictomy | Surgical and medical procedures | MedDRA (10.0) | Systematic Assessment |
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| Angioplasty | Surgical and medical procedures | MedDRA (10.0) | Systematic Assessment |
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| Lunger cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (10.0) | Systematic Assessment |
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| Adenocarcinoma of prostate | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (10.0) | Systematic Assessment |
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| Swelling of legs | General disorders | MedDRA (10.0) | Systematic Assessment |
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| Fracture neck of femur | Injury, poisoning and procedural complications | MedDRA (10.0) | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA (10.0) | Systematic Assessment |
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| Bladder injury | Injury, poisoning and procedural complications | MedDRA (10.0) | Systematic Assessment |
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| Compression fracture | Injury, poisoning and procedural complications | MedDRA (10.0) | Systematic Assessment |
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| Angiography | Investigations | MedDRA (10.0) | Systematic Assessment |
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| Laryngoscopy | Investigations | MedDRA (10.0) | Systematic Assessment |
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| Cytoscopy | Investigations | MedDRA (10.0) | Systematic Assessment |
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| Endoscopy | Investigations | MedDRA (10.0) | Systematic Assessment |
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| Angiogram | Investigations | MedDRA (10.0) | Systematic Assessment |
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| Myocardial infarction | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
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| Pericarditis | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
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| Atrial flutter | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
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| Heart block | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
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| Chest pain | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA (10.0) | Systematic Assessment |
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| COPD exacerbation | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Shortness of breath | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Stroke | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
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| Cataract surgery | Eye disorders | MedDRA (10.0) | Systematic Assessment |
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| Visual field defect | Eye disorders | MedDRA (10.0) | Systematic Assessment |
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| Melaena | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Gastrointestinal bleed | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Rectal bleeding | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Gallstones | Hepatobiliary disorders | MedDRA (10.0) | Systematic Assessment |
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| Gallbladder perforation | Hepatobiliary disorders | MedDRA (10.0) | Systematic Assessment |
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| Obstructive jaundice | Hepatobiliary disorders | MedDRA (10.0) | Systematic Assessment |
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| Hepatic disease | Hepatobiliary disorders | MedDRA (10.0) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
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| Ankle swelling | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
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| Chest infection | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
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| Urinary infection | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
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| Cellulitis of leg | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
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| Cellulitis of arm | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypotension | Vascular disorders | MedDRA (10.0) | Systematic Assessment |
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| Heart failure | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
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| Breathlessness | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Diziness | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
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| Blackout | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
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| Numbness in hands, forearms, elbows | General disorders | MedDRA (10.0) | Systematic Assessment |
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| Sweating | General disorders | MedDRA (10.0) | Systematic Assessment |
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| Feeling sick | General disorders | MedDRA (10.0) | Systematic Assessment |
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| Feeling unwell | General disorders | MedDRA (10.0) | Systematic Assessment |
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| Upset stomach | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Hiatus hernia | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Itchy skin | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
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| Ankle swelling | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
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| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA (10.0) | Systematic Assessment |
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| Numbness in feet | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
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| Other | General disorders | MedDRA (10.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Professor Neil Poulter | Imperial College London | +44(0) 20 7594 3446 | n.poulter@imperial.ac.uk |
| Prot_000.pdf |
| ID | Term |
|---|---|
| D017544 | Aortic Aneurysm, Abdominal |
| ID | Term |
|---|---|
| D001014 | Aortic Aneurysm |
| D000783 | Aneurysm |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D001018 | Aortic Diseases |
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| ID | Term |
|---|---|
| C000608172 | Viacoram |
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