Peripheral Artery DiseasePADNCT04165629
Platelet Reactivity in PAD Undergoing Percutaneous Angioplasty
An observational study of Peripheral Artery Disease and Critical Limb Ischemia, run by Clinical Centre of Serbia at 1 site in Serbia.
Trial summary
Dual antiplatelet therapy has a key role in a prevention of thrombosis of treated artery in patients undergoing percutaneous transluminal angioplasty (PTA). Weak therapeutic response and presence of residual platelet activity is related to high risk for stent thrombosis and it is well in known in coronary artery… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Peripheral Artery Disease, Critical Limb Ischemia, Claudication, Intermittent
- What is being tested?
- Aspirin 300mg and Clopidogrel 300mg
- How many people
- 450 participants
- Where
- 1 siteSerbia
- Study dates
- 1 Jan 2020to 1 Jul 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All patients treated at the Clinic for Vascular and Endovascular Surgery, Clinical Center of Serbia, Belgrade due to PAD (critical limb ischemia {CLI} or intermittent claudication {IC}) with PTA with/without stenting of aorto-iliac, femoro-popliteal and crural disease between January 1st 2020 and January 1st 2022
Who may be able to join
- all patients treated due to PAD with PTA with/without stenting of aorto-iliac, femoro-popliteal and crural disease at the mentioned time period with critical limb ischemia (CLI) or intermittent claudication (IC)
Who cannot join
- younger that 18 and older than 85
- contraindications for Aspirin and Clopidogrel use
- thrombocytopenia (<100 x 10⁹/l)
- thrombocytosis (>450 x 10⁹/l)
- kidney insufficiency (stage 4 and 5)
- more severe anemia (Hgb < 100 g/l)
Show all 14Show fewer
- severe hepatic disorder
- congestive heart failure
- known hemorrhagic disorder
- known malignant disease
- previous use of drugs with known anti-thrombocyte mechanism of action (dipyridamole, NSAID)
- use oral anticoagulant therapy
- use of corticosteroids
- use of drugs that are metabolized threw CYP3A4 (like erythromycin and rifampicin)
Trial locations and contacts
1 site in 1 country.
Serbia1 site, 1 recruiting
- Recruiting
Clinical Center of Serbia
Belgrade, 11000
Petar Zlatanovic, MD, +381644961020, petar91goldy@gmail.com
Tina Novakovic, MD, +38163390321, tinkanova@gmail.com
About this study
Official title: Influence of Platelet Reactivity in Peripheral Arterial Disease Patients Undergoing Percutaneous Angioplasty on Mid-term Outcomes
Dual antiplatelet therapy has a key role in a prevention of thrombosis of treated artery in patients undergoing percutaneous transluminal angioplasty (PTA). Weak therapeutic response and presence of residual platelet activity is related to high risk for stent thrombosis and it is well in known in coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI). However there are few data on the association between a different entity of platelet inhibition on antiplatelet treatment and clinical outcomes in patients with peripheral artery disease (PAD). The aim of this study was to evaluate the degree of on-treatment platelet reactivity, and its association with ischemic and hemorrhagic adverse events at follow up in PAD patients undergoing PTA.
Read the detailed description
This is a single-center observational cohort study. All together 450 patients undergoing and elective PTA (both with and without stenting) who are going to be refereed to the Clinic for Vascular and Endovascular Surgery (based on the previous experience) during the two year period (January 1st 2020 and January 1st 2022) are planned to be involved in this study. All interventions will be performed according to the current standards and the type of the endovascular procedure will be at the discretion of operator. All patients will receive at the day of treatment 300mg of Aspirin and 300mg of Clopidogrel. The day after the procedure platelet function will be assessed by "point-of-care" impedance aggregometry test using the Multiplate analyzer. According to the manufacturer proposition, resistancy on Aspirin will be defined as arachidonic acid receptor (ASPI) value < 600 and ASPI/thrombin receptor activating peptide (TRAP) < 0.5, and for Clopidogrel adenosine diphosphate (ADP) < 500 and ADP/TRAP < 0.5 . After that patients will receive dual antiplatelet therapy (Aspirin 100mg and Clopidogrel 75mg) in the six months period. Follow-up examinations will be scheduled on 1, 6 and 12 months after the intervention. Adherence to antiplatelet treatment will assessed during scheduled or unscheduled examinations. Statistical analysis will be performed using the software package SPSS 20 (SPSS Inc., Chicago, Il, USA). Categorical data will be represented as numbers and percentages. Chi-square test or Fisher exact test as appropriate will be used to compare categorical data. Continuous variables will be represented as mean ± standard deviation and as median and interquartile range, depending on the normality of data. Student's t test or Mann-Whitney U test as appropriate will be used to compare two population groups. We will then assess the ability of ASPI and ADP values to distinguish between patients with and without clinical event at 6 months follow up by receiver-operating characteristic (ROC) curve analysis and the optimal cut-off ASPI and ADP values will be determined by estimating the value resulting in the maximum sum of sensitivity and specificity (area under the curve - AUC). Kaplan-Meier curves with log-rank test will be used to assess difference in the time-to-event end-points. A multivariable Cox proportional hazard model adjusted for clinical and laboratory variables will be performed to evaluate the independent contribution of platelet hyper- or hypo-reactivity to the outcomes. A P-values <0.05 will be considered statistically significant.
- Being tested
- Aspirin 300mg and Clopidogrel 300mg
- Medical subject headings
- Peripheral Arterial Disease, Chronic Limb-Threatening Ischemia, Intermittent Claudication
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aspirin 300mg and Clopidogrel 300mgDrug
Aspirin 300mg and Clopidogrel 300mg on the day of the PTA
| Study group | Role | What they receive |
|---|---|---|
| Aspirin responders | On impedance aggregometry- Multiplate analyzer, if ASPI < 600 or ASPI/TRAP < 0.5 Receives: Drug: Aspirin 300mg and Clopidogrel 300mg | |
| Aspirin non-responders | On impedance aggregometry- Multiplate analyzer, if ASPI > 600 or ASPI/TRAP > 0.5 Receives: Drug: Aspirin 300mg and Clopidogrel 300mg | |
| Clopidogrel responders | On impedance aggregometry- Multiplate analyzer, if ADP < 500 or ADP/TRAP < 0.5 Receives: Drug: Aspirin 300mg and Clopidogrel 300mg | |
| Clopidogrel non-responders | On impedance aggregometry- Multiplate analyzer, if ADP > 500 or ADP/TRAP > 0.5 Receives: Drug: Aspirin 300mg and Clopidogrel 300mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major Adverse Limb Event (MALE)
It includes major amputation, reintervention which could be surgical or repeat angioplasty. Major amputation is defined as amputation above the ankle.
Measured: 6 months
Mortality
All-cause mortality
Measured: 6 months
Secondary outcomes (2)
Major Adverse Cardio- and Cerebrovascular Events (MACCE)
Nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death
Measured: 6 months
Bleeding complications
Major and minor bleeding
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2019
- Study start1 Jan 2020
- Primary completion1 Jan 2022 (estimated)
- Study completion1 Jul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Peripheral Artery DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 450 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Clinical Centre of Serbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Petar Zlatanovic, Clinical Centre of Serbia
- Investigators
- Petar Zlatanovic, MD, Principal investigator, Clinical Center of Serbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04165629
- Sponsor's protocol ID
- Platelet reactivity in PAD
- Acronym
- PAD
- Status last verified
- Jul 2020
- First submitted
- 14 Nov 2019
- Last updated
- 15 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: to be available on request for now
Publications
Spiliopoulos S, Pastromas G, Katsanos K, Kitrou P, Karnabatidis D, Siablis D. Platelet responsiveness to clopidogrel treatment after peripheral endovascular procedures: the PRECLOP study: clinical impact and optimal cutoff value of on-treatment high platelet reactivity. J Am Coll Cardiol. 2013 Jun 18;61(24):2428-2434. doi: 10.1016/j.jacc.2013.03.036. Epub 2013 Apr 16.
PubMed 23602777Grifoni E, Gori AM, Giusti B, Valenti R, Migliorini A, Basili S, Paniccia R, Elmahdy MF, Pulli R, Pratesi C, Antoniucci D, Violi F, Marcucci R. On-Treatment Platelet Reactivity is a Predictor of Adverse Events in Peripheral Artery Disease Patients Undergoing Percutaneous Angioplasty. Eur J Vasc Endovasc Surg. 2018 Oct;56(4):545-552. doi: 10.1016/j.ejvs.2018.06.032. Epub 2018 Jul 17.
PubMed 30025662Leunissen TC, Peeters Weem SM, Urbanus RT, den Ruijter HM, Moll FL, Asselbergs FW, de Borst GJ. High On-Treatment Platelet Reactivity in Peripheral Arterial Disease: A Pilot Study to Find the Optimal Test and Cut Off Values. Eur J Vasc Endovasc Surg. 2016 Aug;52(2):198-204. doi: 10.1016/j.ejvs.2016.04.019. Epub 2016 May 25.
PubMed 27236738Pastromas G, Spiliopoulos S, Katsanos K, Diamantopoulos A, Kitrou P, Karnabatidis D, Siablis D. Clopidogrel responsiveness in patients undergoing peripheral angioplasty. Cardiovasc Intervent Radiol. 2013 Dec;36(6):1493-1499. doi: 10.1007/s00270-013-0577-3. Epub 2013 Feb 14.
PubMed 23408060Spiliopoulos S, Pastromas G. Current status of high on-treatment platelet reactivity in patients with coronary or peripheral arterial disease: Mechanisms, evaluation and clinical implications. World J Cardiol. 2015 Dec 26;7(12):912-21. doi: 10.4330/wjc.v7.i12.912.
PubMed 26730297
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Platelet Reactivity in Peripheral Arterial Disease Patients Undergoing Percutaneous Angioplasty on Mid-term Outcomes
- ClinicalTrials.gov ID
- NCT04165629
- Acronym / sponsor ID
- PAD / Platelet reactivity in PAD
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 450 participants (estimated)
- Lead sponsor
- Clinical Centre of SerbiaUniversity, hospital or other
- Study start
- 1 Jan 2020 (actual)
- Primary completion
- 1 Jan 2022 (estimated)
- Study completion
- 1 Jul 2022 (estimated)
- First posted
- 18 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Dual antiplatelet therapy has a key role in a prevention of thrombosis of treated artery in patients undergoing percutaneous transluminal angioplasty (PTA). Weak therapeutic response and presence of residual platelet activity is related to high risk for stent thrombosis and it is well in known in coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI). However there are few data on the association between a different entity of platelet inhibition on antiplatelet treatment and clinical outcomes in patients with peripheral artery disease (PAD). The aim of this study was to evaluate the degree of on-treatment platelet reactivity, and its association with ischemic and hemorrhagic adverse events at follow up in PAD patients undergoing PTA.
Detailed description
This is a single-center observational cohort study. All together 450 patients undergoing and elective PTA (both with and without stenting) who are going to be refereed to the Clinic for Vascular and Endovascular Surgery (based on the previous experience) during the two year period (January 1st 2020 and January 1st 2022) are planned to be involved in this study. All interventions will be performed according to the current standards and the type of the endovascular procedure will be at the discretion of operator. All patients will receive at the day of treatment 300mg of Aspirin and 300mg of Clopidogrel. The day after the procedure platelet function will be assessed by "point-of-care" impedance aggregometry test using the Multiplate analyzer. According to the manufacturer proposition, resistancy on Aspirin will be defined as arachidonic acid receptor (ASPI) value < 600 and ASPI/thrombin receptor activating peptide (TRAP) < 0.5, and for Clopidogrel adenosine diphosphate (ADP) < 500 and ADP/TRAP < 0.5 . After that patients will receive dual antiplatelet therapy (Aspirin 100mg and Clopidogrel 75mg) in the six months period. Follow-up examinations will be scheduled on 1, 6 and 12 months after the intervention. Adherence to antiplatelet treatment will assessed during scheduled or unscheduled examinations. Statistical analysis will be performed using the software package SPSS 20 (SPSS Inc., Chicago, Il, USA). Categorical data will be represented as numbers and percentages. Chi-square test or Fisher exact test as appropriate will be used to compare categorical data. Continuous variables will be represented as mean ± standard deviation and as median and interquartile range, depending on the normality of data. Student's t test or Mann-Whitney U test as appropriate will be used to compare two population groups. We will then assess the ability of ASPI and ADP values to distinguish between patients with and without clinical event at 6 months follow up by receiver-operating characteristic (ROC) curve analysis and the optimal cut-off ASPI and ADP values will be determined by estimating the value resulting in the maximum sum of sensitivity and specificity (area under the curve - AUC). Kaplan-Meier curves with log-rank test will be used to assess difference in the time-to-event end-points. A multivariable Cox proportional hazard model adjusted for clinical and laboratory variables will be performed to evaluate the independent contribution of platelet hyper- or hypo-reactivity to the outcomes. A P-values <0.05 will be considered statistically significant.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Aspirin responders | – | Drug: Aspirin 300mg and Clopidogrel 300mgOn impedance aggregometry- Multiplate analyzer, if ASPI < 600 or ASPI/TRAP < 0.5 |
| Aspirin non-responders | – | Drug: Aspirin 300mg and Clopidogrel 300mgOn impedance aggregometry- Multiplate analyzer, if ASPI > 600 or ASPI/TRAP > 0.5 |
| Clopidogrel responders | – | Drug: Aspirin 300mg and Clopidogrel 300mgOn impedance aggregometry- Multiplate analyzer, if ADP < 500 or ADP/TRAP < 0.5 |
| Clopidogrel non-responders | – | Drug: Aspirin 300mg and Clopidogrel 300mgOn impedance aggregometry- Multiplate analyzer, if ADP > 500 or ADP/TRAP > 0.5 |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All patients treated at the Clinic for Vascular and Endovascular Surgery, Clinical Center of Serbia, Belgrade due to PAD (critical limb ischemia {CLI} or intermittent claudication {IC}) with PTA with/without stenting of aorto-iliac, femoro-popliteal and crural disease between January 1st 2020 and January 1st 2022
Key inclusion criteria (1 listed)
- all patients treated due to PAD with PTA with/without stenting of aorto-iliac, femoro-popliteal and crural disease at the mentioned time period with critical limb ischemia (CLI) or intermittent claudication (IC)
Key exclusion criteria (14 listed)
- younger that 18 and older than 85
- contraindications for Aspirin and Clopidogrel use
- thrombocytopenia (<100 x 10⁹/l)
- thrombocytosis (>450 x 10⁹/l)
- kidney insufficiency (stage 4 and 5)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aspirin 300mg and Clopidogrel 300mgAspirin 300mg and Clopidogrel 300mg on the day of the PTA | Drug | Aspirin non-responders, Aspirin responders, Clopidogrel non-responders, Clopidogrel responders |
Primary outcome
Major Adverse Limb Event (MALE)
Time frame: 6 months
It includes major amputation, reintervention which could be surgical or repeat angioplasty. Major amputation is defined as amputation above the ankle.
Mortality
Time frame: 6 months
All-cause mortality
2 secondary outcomes
Major Adverse Cardio- and Cerebrovascular Events (MACCE)
Time frame: 6 months
Bleeding complications
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2020.
- Background: PubMed 23602777Spiliopoulos S, Pastromas G, Katsanos K, Kitrou P, Karnabatidis D, Siablis D. Platelet responsiveness to clopidogrel treatment after peripheral endovascular procedures: the PRECLOP study: clinical impact and optimal cutoff value of on-treatment high platelet reactivity. J Am Coll Cardiol. 2013 Jun 18;61(24):2428-2434. doi: 10.1016/j.jacc.2013.03.036. Epub 2013 Apr 16.
- Background: PubMed 30025662Grifoni E, Gori AM, Giusti B, Valenti R, Migliorini A, Basili S, Paniccia R, Elmahdy MF, Pulli R, Pratesi C, Antoniucci D, Violi F, Marcucci R. On-Treatment Platelet Reactivity is a Predictor of Adverse Events in Peripheral Artery Disease Patients Undergoing Percutaneous Angioplasty. Eur J Vasc Endovasc Surg. 2018 Oct;56(4):545-552. doi: 10.1016/j.ejvs.2018.06.032. Epub 2018 Jul 17.
- Background: PubMed 27236738Leunissen TC, Peeters Weem SM, Urbanus RT, den Ruijter HM, Moll FL, Asselbergs FW, de Borst GJ. High On-Treatment Platelet Reactivity in Peripheral Arterial Disease: A Pilot Study to Find the Optimal Test and Cut Off Values. Eur J Vasc Endovasc Surg. 2016 Aug;52(2):198-204. doi: 10.1016/j.ejvs.2016.04.019. Epub 2016 May 25.
- Background: PubMed 23408060Pastromas G, Spiliopoulos S, Katsanos K, Diamantopoulos A, Kitrou P, Karnabatidis D, Siablis D. Clopidogrel responsiveness in patients undergoing peripheral angioplasty. Cardiovasc Intervent Radiol. 2013 Dec;36(6):1493-1499. doi: 10.1007/s00270-013-0577-3. Epub 2013 Feb 14.
- Background: PubMed 26730297Spiliopoulos S, Pastromas G. Current status of high on-treatment platelet reactivity in patients with coronary or peripheral arterial disease: Mechanisms, evaluation and clinical implications. World J Cardiol. 2015 Dec 26;7(12):912-21. doi: 10.4330/wjc.v7.i12.912.
- Individual participant dataSharing planned: Undecided. to be available on request for now
Related trials for Peripheral Artery Disease
Active, not recruiting
SUCCESS (SelUtion, Safety, effiCaCy, hEalth economicS and promS) PTA Study
Peripheral Artery Disease
RecruitingPhase 3
Reducing Adverse Vascular Outcomes With Factor XI Inhibition in Adult Participants With Peripheral Artery Disease
Peripheral Artery Disease (PAD)
Recruiting
The THOR IDE Study
Peripheral Artery Disease, Peripheral Artery Stenosis
Not yet recruiting
Daily Stretching to Improve Walking in Older Patients With Peripheral Artery Disease: The STRETCH PAD Study
Peripheral Artery Disease (PAD), Intermittent Claudication
Recruiting
WIN Ratio Analysis to Determine a Strategy of Non- Invasive SUpport for Respiratory Failure in the EmeRgency Department
Acute Hypoxic Respiratory Failure, Acute Respiratory Distress Syndrome (ARDS)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Petar Zlatanovic, MD principal investigator
Clinical Center of Serbia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Peripheral Artery Disease and Critical Limb Ischemia, run by Clinical Centre of Serbia at 1 site in Serbia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Serbia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Petar Zlatanovic, MD (+381644961020, petar91goldy@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major Adverse Limb Event (MALE) (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04165629, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2020.