Personalised antiplatelet therapy for patients with narrowing/blocked blood supply to their legs
| ISRCTN | ISRCTN10495682 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10495682 |
| IRAS number | 293977 |
| ClinicalTrials.gov number | NCT06047002 |
| Secondary identifying numbers | IRAS 293977, 0829 |
- Submission date
- 18/10/2023
- Registration date
- 01/11/2023
- Last edited
- 13/12/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Plain English summary of protocol
Background and study aims
Peripheral arterial disease (PAD) is a condition where the blood vessels in the legs get blocked. It affects one out of every five adults over the age of 65. As it is the main cause of amputations, the NHS performs over 20,000 operations every year to prevent them. People with PAD benefit from tablets to thin their blood as this improves outcomes after surgery and prevents heart attacks and strokes. The main tablets for this purpose are called aspirin and clopidogrel. These tablets work well in most people, but up to a third of patients do not get any benefit from them, as their bodies cannot process them. This is called resistance to therapy (RT). Because blood thinning is particularly important after operations people with RT may be at higher risk of their operation failing leading to amputation and/or problems such as heart attacks and strokes. Testing for RT has not traditionally been performed because it requires complex laboratory procedures. Recent developments in technology now mean that bedside tests are available for RT. In this study, a simple bedside test for RT will be used to see if patients with severe PAD have RT and whether this affects their risk of complications after an operation. If it is found that RT does affect outcomes for patients with PAD, the information obtained will be used to plan future research to determine if changing blood thinning therapy in people with RT improves their outcomes.
Who can participate?
Adult patients aged 18 years old and over with PAD
What does the study involve?
The study involves a face-to-face baseline appointment where information will be collected about the participants and their medical health. During this appointment, blood samples will be taken to assess any response to the blood thinning medication currently prescribed. Participants will then be contacted in 6 and 12 months via telephone for a 15-minute conversation regarding their medical health.
What are the possible benefits and risks of participating?
Although participants will not receive any extra benefit from taking part, research like this helps to continually improve the treatment and care provided to all patients now and in the future. There are no extra risks involved in taking part in this research. Participants will not be asked to try any new treatments. Choosing to participate in any of the additional assessments has the main disadvantage of having to give up some time. In addition, bruising may be experienced when blood samples are taken.
Where is the study run from?
University of Leicester (UK)
When is the study starting and how long is it expected to run for?
November 2021 to March 2025
Who is funding the study?
John and Lucille van Geest Foundation (UK)
Who is the main contact?
Sarah Jane Messeder, sjm104@leicester.ac.uk
Contact information
Public, Scientific, Principal Investigator
Vascular Research Office
Clinical Sciences Wing
University of Leicester
Glenfield Hospital
Groby Road
Leicester
LE3 9QP
United Kingdom
 ORCID ID |
0000-0003-4104-2904 |
|---|---|
| Phone | +44 (0)116 250 2381 |
| sjm104@leicester.ac.uk |
Public
Vascular Research Office
Clinical Sciences Wing
University of Leicester
Glenfield Hospital
Groby Road
Leicester
LE3 9QP
United Kingdom
| Phone | +44 (0)116 250 2381 |
|---|---|
| ame29@leicester.ac.uk |
Study information
| Study design | Prospective observational cohort study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Hospital, Medical and other records, Telephone |
| Study type | Diagnostic, Prevention |
| Participant information sheet | 44438_PIS_v1.3_17May2023.pdf |
| Scientific title | Personalised ANtiplatelet THERapy for patients with symptomatic Peripheral Arterial Disease (PANTHER-PAD) |
| Study acronym | PANTHER-PAD |
| Study objectives | Identification of patients with peripheral arterial disease with resistance to therapy will allow individualisation of anti-platelet treatment, preventing limb loss and reducing the risk of death |
| Ethics approval(s) |
Approved 23/12/2021, East Midlands - Nottingham 1 Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS, United Kingdom; +44 (0)207 104 8115; nottingham1.rec@hra.nhs.uk), ref: 21/EM/0260 |
| Health condition(s) or problem(s) studied | Resistance to antiplatelet therapy in patients with peripheral arterial disease |
| Intervention | Peripheral arterial disease (PAD) is a condition where the blood vessels in the legs get blocked. It affects one out of every five adults over the age of 65. As it is the main cause of amputations, the NHS performs over 20,000 operations every year to prevent them. People with PAD benefit from tablets to thin their blood as this improves outcomes after surgery and prevents heart attacks and strokes. The main tablets for this purpose are aspirin and clopidogrel. These work in most people, but up to a third of patients do not get any benefit from them, as their bodies cannot process them. This is called resistance to therapy (RT). Since blood thinning is particularly important after operations, people with RT may be at higher risk of their operation failing leading to amputation and/or problems such as heart attacks and strokes. Testing for RT has not traditionally been performed because it requires complex laboratory procedures. Recent development in technology now means that bedside tests are available for RT. In this study, a simple bedside test for RT will be used to see how many patients with severe PAD have RT and whether this affects their risk of complications after an operation. If RT is found to affect outcomes for patients with PAD, the information obtained will be used to plan future research to determine if changing blood thinning therapy in people with PAD improves their outcomes after surgery. Primary objective: To examine the feasibility of using the VerifyNow PRU and Aspirin assays to obtain estimates of the prevalence of resistance to antiplatelet therapy (aspirin & clopidogrel) in patients with symptomatic PAD. [ Time Frame: 18 months ] Prevalence of resistance to aspirin and clopidogrel will be calculated as: Prevalence = (Number of patients resistant/Total study population) * 100 The VerifyNow PRU Test (CPT85576) is reported as P2Y12 Reaction Units (PRU). PRU measures the extent of platelet aggregation in the presence of a P2Y12 inhibitor. <180 PRU - suggests P2Y12 inhibitor effect 180-376 PRU - suggests lack of P2Y12 inhibitor effect. The VerifyNow Aspirin (CPT 85576) test is reported as Aspirin Reaction Units (ARU). ARU measures the extent of platelet aggregation in the presence of Arachidonic acid. </= 549 ARU - Evidence of platelet dysfunction due to aspirin > 550 ARU - No evidence of aspirin-induced platelet dysfunction. Secondary objective: To examine whether resistance to antiplatelet therapy is associated with major adverse cardiac or limb events during the follow-up interval of one year [ Time Frame: 18 months ] Risk ratio = Cumulative incidence of major adverse cardiac/limb events in the Resistant Groups/Cumulative Incidence of Major events in the non-Resistant group Major adverse cardiac events = myocardial infarction, stroke, cardiovascular death Major adverse limb events = major amputation, acute limb ischaemia, re-operation. Events will be assessed through interrogation of electronic medical records and phone calls with participants at both 6 months and one-year follow up. |
| Intervention type | Other |
| Primary outcome measure | Feasibility of using the VerifyNow PRU and Aspirin assays measured using the obtained estimates of the prevalence of resistance to antiplatelet therapy (aspirin & clopidogrel) in patients with symptomatic peripheral arterial disease at 18 months |
| Secondary outcome measures | To examine whether resistance to antiplatelet therapy is associated with major adverse cardiac or limb events during the follow-up interval of one year measured using the risk ratios in the resistant and non-resistant groups of cumulative incidence of major adverse cardiac/limb events assessed through interrogation of electronic medical records and phone calls with participants at both 6 months and one year follow up |
| Overall study start date | 20/11/2021 |
| Completion date | 31/03/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 80 |
| Total final enrolment | 87 |
| Key inclusion criteria | 1. Aged 18 years old and over 2. Severely symptomatic aorto-iliac and infra-inguinal peripheral arterial disease 3. Ability to provide written informed consent 4. Patients on antiplatelet therapy |
| Key exclusion criteria | 1. Aged 17 years old and under 2. Unable or unwilling to provide written informed consent 3. Acute limb ischaemia of the lower limb 4. Aneurysmal disease of the arteries of the lower limb 5. Severe diabetic foot sepsis 6. A known history of clotting disorders 7. Inherited bleeding disorders |
| Date of first enrolment | 25/05/2023 |
| Date of final enrolment | 14/03/2024 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Leicester
LE3 9QP
United Kingdom
Sponsor information
University/education
Research Governance Office
Research & Enterprise Division
University of Leicester
Leicester General Hospital
Gwendolen Road
Leicester
LE1 7RH
England
United Kingdom
| Phone | +44 (0)116 258 4761 |
|---|---|
| rgosponsor@leicester.ac.uk | |
| Website | https://le.ac.uk/research/regi |
"ROR" |
https://ror.org/04h699437 |
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- THE JOHN AND LUCILLE VAN GEEST FOUNDATION
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/12/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Published as a supplement to the results publication |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The datasets generated and/or analysed during the current study will be published as a supplement to the results publication |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 1.3 | 17/05/2023 | 24/10/2023 | No | Yes |
Additional files
Editorial Notes
13/12/2024: The following changes were made to the study record:
1. The recruitment end date was changed from 31/12/2023 to 14/03/2024.
2. The overall study end date was changed from 31/12/2024 to 31/03/2025.
3. Total final enrolment added.
24/10/2023: Study's existence confirmed by the East Midlands - Nottingham 1 Research Ethics Committee, HRA (UK).
