Multicentric Study on Clopidogrel Resistance in DAPT for CAS (MULTI-RESCLOSA)

July 1, 2026 updated by: Daniela Mazzaccaro, IRCCS Policlinico S. Donato

MULTIcentric Study About RESistance to CLOpidogrel in Dual Antiplatelet Therapy for Carotid Stenting

Spontaneous prospective observational multicentre pharmacological study that aims to evaluate whether, from a statistical point of view, there is a significant difference between the use of Ticagrelor in "non-responders" patients to Clopidogrel undergoing carotid stenting and Clopidogrel in "responders" undergoing carotid stenting, in the onset of death and major adverse cardiovascular events (MACE) and bleeding events, 1 and 3 months after the procedure. Furthermore, the study aims to evaluate the possible preoperative clinical and pharmacological factors most associated with the phenomenon of resistance to Clopidogrel.

Inclusion criteria:

The data will be collected on adult patients (age> 18 years) who have given their consent to participate in the study, belonging to the U.O. of Vascular Surgery of the IRCCS Policlinico San Donato and the U.O. of Vascular Surgery of the participating centers and there subjected to the treatment of carotid stenosis by stenting technique.

Exclusion criteria:

Those patients who are minors, who have not given their consent to participate in the study, or who have carotid stenosis not susceptible to intervention by stenting will be excluded from the study. Pregnant or lactating women will also be excluded from the study (such as situations in which carotid stenting is contraindicated regardless of the execution of the study).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Patients' records will be reviewed for clinical data (age, sex, height and weight), the presence of cardiovascular risk factors (diabetes mellitus, hypertension, dyslipidemia, smoking habits, coronary artery disease, chronic obstructive pulmonary disease), features of the carotid plaque (type of plaque and degree of carotid stenosis, according to ECST measurement), and status of the contralateral carotid artery. The occurrence of preoperative neurologic symptoms within the previous 6 months will also be recorded, as evaluated by the neurologist.

Preoperative and postoperative drug intake will be investigated, with particular attention to statins, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, antiplatelet therapy and anticoagulant therapy.

Laboratory data such as serum creatinine, platelet counts, Red blood cell Distribution Width (RDW), Prothrombin Time (PT), International Normalized Ratio (INR), activated Partial Thromboplastin Time (aPTT) and ratio will be also assessed.

After operation, patients will be followed up three times in the first year (at 1 month, 6 months, and 12 months) and annually thereafter, using ultrasound. An angio-Computed Tomography scan will be required when complications were detected at ultrasound examination. During follow-up, data will be collected about the occurrence of death, stent thrombosis, cerebrovascular events, cardiac events, major haemorrhagic events.

Determination of the effectiveness of antiplatelet drugs The effectiveness of antiplatelet drugs will be evaluated through the impedance aggregometry test, conducted with the Multiplate® platelet function analysis V2.03.11 (Roche, Basel, Switzerland).

Multiplate® technology is based on the principle of electrical impedance aggregometry for the determination of platelet function on whole blood.

The instrument has five independent channels for parallel measurement and is connected to a computer equipped with specific software for the analysis and display of results in real time.

The blood and reagents are placed in a disposable cuvette containing two pairs of electrodes, representing two independent sensor units for a duplicate measurement. The platelets activated by the specific agonist adhere to the metal surface of the sensors, forming an insulating layer and increasing the electrical impedance between the electrodes. The change in impedance due to adhesion and platelet aggregation is represented as a function of time. The area included within the aggregation curve, used to measure aggregation, is expressed in arbitrary aggregation units (U). Since the change in impedance is measured simultaneously on two sensors, the results of each test are expressed as the average value of the two aggregation curves obtained.

Blood sampling to assess platelet aggregation was performed at the patient's hospitalization (in the event that he was already taking clopidogrel), or at least 6 hours after the start of antiplatelet therapy with clopidogrel.

The aggregometry test evaluates the efficacy of salicylates (ASPI-test, aggregation with the use of arachidonic acid: normal reference values 71-115 U) and the efficacy of drugs that act on the adenosine diphosphate (ADP) receptor such as thienopyridines. (ADP-test, ADP-triggered aggregation: normal reference values 57-113 U), compared to the positive control for platelet reactivity by the thrombin-receptor activating peptide (TRAP)-6 (TRAP-test: normal reference values 84-128 U).

In particular, 4 mL of either arterial or venous whole blood will be collected in a tube containing the specific anticoagulant hirudin. Three hundred µL of whole blood diluted with 300 µL of physiological solution will be placed in a disposable cuvette with the aid of an automatic pipette, and left to incubate at 37 ºC for 3 minutes. After incubation, a specific agonist will be added for the required exam. The platelet aggregation value will be measured over the next 6 minutes.

The effectiveness of clopidogrel is defined by the evidence of ADP-test which results to be under normal reference values, otherwise the patient is considered to be resistant to the effect of the drug.

Study Type

Observational

Enrollment (Estimated)

1140

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Milan
      • San Donato Milanese, Milan, Italy, 20097
        • Recruiting
        • IRCCS Policlinico San Donato
        • Sub-Investigator:
          • Giovanni Nano, MD
        • Contact:
        • Sub-Investigator:
          • Gianluca Faggioli, MD
        • Sub-Investigator:
          • Giovanni Pratesi, MD
        • Sub-Investigator:
          • Roberto Silingardi, MD
        • Sub-Investigator:
          • Michele Antonello, MD
        • Sub-Investigator:
          • Marco Ranucci, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients who undergo carotid stenting for a significant carotid stenosis and who are treated with dual antiplatelet therapy using ASA + clopidogrel

Description

Inclusion Criteria:

  • adult patients (age> 18 years)
  • patients who have given their consent to participate in the study, belonging to the U.O. of Vascular Surgery of the IRCCS Policlinico San Donato and the U.O. of Vascular Surgery of the participating centers and subjected to the treatment of carotid stenosis by stenting technique.

Exclusion Criteria:

  • underage patients
  • patients who have not given their consent to participate in the study,
  • patients who have carotid stenosis not susceptible to intervention by stenting
  • pregnant or lactating women (such as situations in which carotid stenting is contraindicated regardless of the execution of the study).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Clopidogrel
Patients who undergo carotid stenting and dual antiplatelet therapy with ASA + clopidogrel and whose aggregometry test shows correct response to the effect of clopidogrel
Drug: Clopidogrel
All patients will undergo carotid stenting and dual antiplatelet therapy with ASA + clopidogrel
Ticagrelor
Patients who undergo carotid stenting and dual antiplatelet therapy with ASA + clopidogrel and whose aggregometry test shows incorrect response to the effect of clopidogrel, therefore therapy is switched to ASA + ticagrelor
Drug: Ticagrelor
All patients will undergo carotid stenting and dual antiplatelet therapy with ASA + clopidogrel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Death
Time Frame: 1 month
Outpatient visit
1 month
Death
Time Frame: 3 months
Outpatient visit
3 months
MACE
Time Frame: 1 month
Major Adverse Cardiovascular Events, Outpatient visit
1 month
MACE
Time Frame: 3 months
Major Adverse Cardiovascular Events, Outpatient visit
3 months
Occurrence of major hemorrhagic events
Time Frame: 1 month
Outpatient visit
1 month
Occurrence of major hemorrhagic events
Time Frame: 3 months
Outpatient visit
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS Policlinico S. Donato

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 2, 2021

Primary Completion (Estimated)

September 30, 2030

Study Completion (Estimated)

December 31, 2030

Study Registration Dates

First Submitted

September 28, 2022

First Submitted That Met QC Criteria

September 30, 2022

First Posted (Actual)

October 4, 2022

Study Record Updates

Last Update Posted (Actual)

July 2, 2026

Last Update Submitted That Met QC Criteria

July 1, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MULTI-RESCLOSA v.1 16-2-21

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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