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Trial registered on ANZCTR


Registration number
ACTRN12618000523202
Ethics application status
Approved
Date submitted
12/01/2018
Date registered
10/04/2018
Date last updated
28/04/2021
Date data sharing statement initially provided
14/02/2020
Date results information initially provided
28/04/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Antiplatelet therapy following peripheral endovascular intervention
Scientific title
The effect of anti platelet therapy on amputation-free survival following lower limb peripheral endovascular intervention for patients with peripheral arterial disease.
Secondary ID [1] 293742 0
None
Universal Trial Number (UTN)
U1111-1207-3831
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Peripheral arterial disease 306110 0
Condition category
Condition code
Cardiovascular 305237 305237 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Patients undergoing peripheral endovascular intervention (angioplasty and/or stenting of the iliac, femoral, popliteal, tibial or peroneal arteries) for treatment of peripheral arterial disease at Aneurin Bevan University Health Board between January 2010 and January 2017 and not receiving therapeutic anticoagulation following the procedure. Patients will be followed up for a minimum of 12 months following their procedure for assessment of outcomes.
Exposure arm is according to the antiplatelet agents documented in the medical notes as being given following the procedure.
Arm 1: Neither Aspirin at a dose of at least 75mg daily, nor any P2Y12 inhibitor (this is likely to be clopidogrel 75mg daily in the majority of cases, but could be ticlopidine, prasugrel, ticagrelor, or any other P2Y12 inhibitor at a standard therapeutic dose) given orally following peripheral endovascular intervention.
Arm 2: Aspirin at a dose of at least 75mg daily given orally following peripheral endovascular intervention without concomitant P2Y12 inhibitor (this is likely to be clopidogrel 75mg daily in the majority of cases, but could be ticlopidine, prasugrel, ticagrelor, or any other P2Y12 inhibitor at a standard therapeutic dose).
Arm 3: P2Y12 inhibitor given orally following peripheral endovascular intervention (this is likely to be clopidogrel 75mg daily in the majority of cases, but could be ticlopidine, prasugrel, ticagrelor, or any other P2Y12 inhibitor at a standard therapeutic dose) without concomitant oral aspirin at a dose of 75mg daily or more.
Arm 4: Aspirin at a dose of at least 75mg daily given orally AND a P2Y12 inhibitor given orally following peripheral endovascular intervention (this is likely to be clopidogrel 75mg daily in the majority of cases, but could be ticlopidine, prasugrel, ticagrelor, or any other P2Y12 inhibitor at a standard therapeutic dose).
Patients receiving antiplatelet agents other than aspirin or a P2Y12 inhibitor will be included and their treatment arm determined according to the rules above. Treatment administered is at the discretion of the treating clinician - all treatments are routinely administered as part of standard care and documented in the medical notes. Treatment arm will be allocated based on the treatment given immediately following the procedure, not the duration of treatment.
Intervention code [1] 299993 0
Not applicable
Comparator / control treatment
This is a four arm study comparing the effects of treatment with aspirin vs. P2Y12 inhibitor (usually clopidogrel but includes any P2Y12 inhibitor at a standard therapeutic dose) vs. both vs. neither following their endovascular treatment.
Control group
Active

Outcomes
Primary outcome [1] 304391 0
Amputation-free survival (efficacy outcome), as assessed by linkage to electronic medical records
Timepoint [1] 304391 0
Assessed retrospectively at date of study commencement, which will be a minimum of 12 months following the index procedure.
Primary outcome [2] 304392 0
Freedom from major bleeding (safety outcome), defined as bleeding events requiring either presentation to the emergency room or hospital admission as assessed by linkage to electronic medical records
Timepoint [2] 304392 0
Assessed retrospectively at date of study commencement, which will be a minimum of 12 months following the index procedure.
Secondary outcome [1] 341796 0
Overall survival as assessed by linkage to electronic medical records
Timepoint [1] 341796 0
Assessed retrospectively at date of study commencement, which will be a minimum of 12 months following the index procedure.
Secondary outcome [2] 341797 0
Freedom from major limb amputation events as assessed by linkage to electronic medical records
Timepoint [2] 341797 0
Assessed retrospectively at date of study commencement, which will be a minimum of 12 months following the index procedure.
Secondary outcome [3] 341798 0
Freedom from target lesion revascularisation as assessed by linkage to electronic medical records
Timepoint [3] 341798 0
Assessed retrospectively at date of study commencement, which will be a minimum of 12 months following the index procedure.
Secondary outcome [4] 341799 0
Freedom from target limb revascularisation as assessed by linkage to electronic medical records
Timepoint [4] 341799 0
Assessed retrospectively at date of study commencement, which will be a minimum of 12 months following the index procedure.
Secondary outcome [5] 341800 0
Wound healing as assessed by linkage to electronic medical records
Timepoint [5] 341800 0
Assessed retrospectively at date of study commencement, which will be a minimum of 12 months following the index procedure.

Eligibility
Key inclusion criteria
• Patients undergoing primary angioplasty or stenting with bare metal or drug-eluting stents of the infra-renal aorta; common or external iliac arteries; common, superficial or deep femoral artery; popliteal artery; tibio-peroneal trunk; anterior or posterior tibial artery or peroneal artery or any pedal artery for stenotic or occlusive peripheral arterial disease
• Patients undergoing primary angioplasty or stenting of a stenosis in a surgical bypass graft running between two of the included arteries mentioned above
• Patients already included in the study by virtue of treatment of the contralateral limb, who subsequently undergo endovascular therapy to the other leg
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Patients undergoing treatment for aneurysmal disease, or for a complication of treatment of aneurysmal disease
• Lesions treated with covered stent grafts
• Patients already recruited into the study and undergoing repeated endovascular therapy to the same limb
• Patients undergoing treatment proximal to the infra-renal aorta, to the upper limb, head and next vessels, mesenteric or renal vessels
• Patients undergoing diagnostic angiogram only, with no attempt made to perform angioplasty
• Patients undergoing intra-arterial embolectomy, thrombectomy or thrombolysis, other than those where this is commenced immediately following primary angioplasty or stenting in order to treat a complication.
• Venous procedures (e.g. stenting of veins following DVT)
• Angioplasty or stenting of arterio-venous fistulas
• Treatment of arterio-venous malformations
• Patients receiving therapeutic anticoagulation in the form of therapeutic dose low molecular weight heparin; or warfarin with a target international normalised ratio of 2.0 or more; or a direct oral anticoagulant such as apixaban, dabigatran or rivaroxaban at therapeutic dosage.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Retrospective
Statistical methods / analysis
Prior to analysis, data will be anonymised. Both adjusted and unadjusted analysis will be performed. Adjusted analysis will use stepwise regression analysis which minimises Akaike’s Information Criterion to develop parsimonious multivariate Cox regression models for the outcomes. Given the retrospective nature of the study, it is likely that significant issues with missing data may arise. We therefore plan to deploy multiple imputation methodology to account for missing data items where missing data rates are less than 40% in a given variable. Where rates are higher than 40%, the variable will be excluded from analysis.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
16/04/2018
Actual
16/04/2018
Date of last participant enrolment
Anticipated
2/07/2018
Actual
28/09/2018
Date of last data collection
Anticipated
3/09/2018
Actual
31/01/2020
Sample size
Target
629
Accrual to date
Final
516
Recruitment outside Australia
Country [1] 9476 0
United Kingdom
State/province [1] 9476 0

Funding & Sponsors
Funding source category [1] 298354 0
Government body
Name [1] 298354 0
Aneurin Bevan University Health Board
Country [1] 298354 0
United Kingdom
Primary sponsor type
Government body
Name
Aneurin Bevan University Health Board
Address
Clinical Research and Innovation Centre
St Woolos Hospital
Block C
Stow Hill
Newport, South Wales
NP20 4SZ
Country
United Kingdom
Secondary sponsor category [1] 297476 0
Individual
Name [1] 297476 0
Christopher P Twine
Address [1] 297476 0
Vascular Institute
Royal Gwent Hospital
Cardi Road
Newport
NP20 2UB
Country [1] 297476 0
United Kingdom

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299349 0
Aneurin Bevan University Health Board Research Risk Review Committee
Ethics committee address [1] 299349 0
R&D Department
Clinical Research & Innovation Centre
St Woolos Hospital
Block C, Stow Hill
Newport, South Wales
NP20 4SZ
Ethics committee country [1] 299349 0
United Kingdom
Date submitted for ethics approval [1] 299349 0
01/11/2016
Approval date [1] 299349 0
16/11/2016
Ethics approval number [1] 299349 0
SA/710/16

Summary
Brief summary
Peripheral endovascular intervention describes a group of procedures which are used to open up arteries away from the heart which have been blocked by cardiovascular disease. The past decade has seen a huge expansion in these interventions, with cases increasing threefold in England over the past decade from around 12,000 cases in 2004-5 to over 33,000 in 2014-15 according to Hospital Episode Statistics. Despite this expansion, there is a dearth of high quality evidence regarding the optimal medical management of these patients. A high quality (Cochrane) review of anti-platelet and anticoagulant therapy in this context found only small trials which enrolled a mixture of patients with varying levels of disease, affecting a variety of peripheral arteries, in a mixture of diabetic and non-diabetic patients. Current practice is therefore varied, with some practitioners borrowing evidence from cardiology trials. Doing so is attractive, as multiple large randomised controlled trials of coronary endovascular interventions have enrolled thousands of patients. Good evidence supports the use of dual anti-platelet therapy with aspirin and a thienopyridine derived agent such as clopidogrel in this setting. However there are key differences between coronary and peripheral arterial intervention. In coronary disease the majority of trial evidence relates to sudden vessel blockages (acute vessel thrombosis) leading to myocardial infarction. By contrast, peripheral intervention is principally performed in patients with stable disease. Results of a large trial have resulted in a move towards routine stent implantation (placing a permanent metal tube within the artery in an attempt to keep it open) in coronary intervention, whereas the evidence for lower limb endovascular procedures has led the UK National Institute for Health and Care Excellence to recommend angioplasty (using a balloon to open up an artery) without stenting.

Our hypothesis, which is borne out by the limited amount of research that currently exists in this area, is that dual anti-platelet therapy following peripheral endovascular intervention has significant benefits in terms of both increasing the likelihood that arteries which have been re-opened by angioplasty will remain open (lesion patency), and also reducing the chances that the patient will suffer other cardiovascular events in the early post-procedural period. We will perform a review of patients treated with peripheral endovascular intervention in our region since 2010 to assess the effect of different anti-platelet medications on outcomes. The primary outcome will be amputation free survival. Secondary outcomes will be limb salvage, overall survival and the need for further intervention.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 2317 2317 0 0
/AnzctrAttachments/374271-Service Evaluation Approval letter - SA-710-16.pdf (Ethics approval)

Contacts
Principal investigator
Name 80142 0
Mr Christopher Twine
Address 80142 0
Vascular Institute
Royal Gwent Hospital
Cardiff Road
Newport
NP20 2UB
Country 80142 0
United Kingdom
Phone 80142 0
+44 1633 234124
Fax 80142 0
+44 1633 234113
Email 80142 0
[email protected]
Contact person for public queries
Name 80143 0
Graeme Ambler
Address 80143 0
Division of Population Medicine
Cardiff University School of Medicine
3rd Floor Neuadd Meirionnydd
Heath Park
Cardiff
CF14 4YS
Country 80143 0
United Kingdom
Phone 80143 0
+44 1633 234124
Fax 80143 0
+44 1633 234113
Email 80143 0
[email protected]
Contact person for scientific queries
Name 80144 0
Graeme Ambler
Address 80144 0
Division of Population Medicine
Cardiff University School of Medicine
3rd Floor Neuadd Meirionnydd
Heath Park
Cardiff
CF14 4YS
Country 80144 0
United Kingdom
Phone 80144 0
+44 1633 234124
Fax 80144 0
Email 80144 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes June 11 2020. Single versus dual antiplatelet the... [More Details]

Documents added automatically
No additional documents have been identified.