CRETA (Clopidogrel Responsiveness in Essential ThrombocithemiA) (CRETA)

Evaluation of Response to Clopidogrel in Patients With Essential Thrombocythemia

Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm associated with increased platelet production and activation, leading to a high risk of thrombotic complications. Low-dose aspirin is the standard antiplatelet therapy for thrombosis prevention; however, the accelerated platelet turnover characteristic of ET results in rapid recovery of platelet function, making once-daily aspirin insufficient in many patients. Consequently, twice-daily low-dose aspirin is currently recommended to achieve adequate and sustained platelet inhibition.

For patients intolerant to aspirin, clopidogrel 75 mg/day is the approved alternative. Clopidogrel irreversibly inhibits the platelet P2Y12 receptor, but its pharmacodynamic effect is highly variable because it is a prodrug requiring metabolic activation. Studies in non-ET populations have shown that higher clopidogrel doses (150 mg/day) provide stronger and more consistent platelet inhibition without significantly increasing bleeding risk.

Evidence on clopidogrel use in ET is limited, but available data suggest that standard-dose therapy may result in inadequate platelet inhibition, potentially reducing antithrombotic efficacy. Platelet function testing can identify patients with high residual platelet reactivity ("poor responders"), who may benefit from dose escalation. Therefore, in ET patients requiring clopidogrel therapy, assessment of platelet responsiveness may help optimize treatment, ensuring adequate platelet inhibition and potentially improving protection against thrombotic events.

Study Overview

• Status: Not yet recruiting
• Conditions: Essential Thrombocythemia
• Intervention / Treatment: Diagnostic test: VerifyNow P2Y12 assay

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Elena Rossi; Phone Number: +39 0630154206; Email: elena.rossi@policlinicogemelli.it

Study Locations

• Italy
  • Pescara, Italy, 65124
    • Azienda USL di Pescara - Ospedale Santo Spirito
    • Contact: Paola Ranalli; Email: paola.ranalli@asl.pe.it
    • Principal Investigator: Paola Ranalli
  • Torino, Italy, 10126
    • AOU Citta della Salute e della Scienza di Torino
    • Principal Investigator: Eloise Beggiato
    • Contact: Eloise Beggiato; Email: ebeggiato@cittadellasalute.to.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Consecutive Patients with ET, with an approved indication for clopidogrel therapy (i.e., aspirin intolerance) and a documented good or poor response to the standard 75 mg od dose of clopidogrel at maintenance, as assessed by the standard VN-P2Y12 poinr of care, platelet function test.

At least 50 patients will be enrolled, based on the current records of the participating Centers.

Description

Inclusion Criteria:

1. Male or female subjects age ≥ 18 years;
2. Confirmed diagnosis of ET according to the 2022 WHO classification criteria30;
3. Patients treated with clopidogrel 75 mg od as antithrombotic prophylaxis since at least 3 weeks, as per the indication of the referring hematologist;
4. Ability to understand the nature of the study and voluntarily provide written informed consent patients whose responsiveness to the standard clopidogrel regimen was determined, based on clinical practice, using the VN-P2Y12 method.

Exclusion Criteria:

1. Platelet count >1,000,000/μL on three separate determinations within the 2 months prior to enrollment;
2. Need for anticoagulant therapy;
3. Concomitant use of other antiplatelet agents;
4. Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) (i.e > 3 days per week);
5. Chronic corticosteroid therapy exceeding a daily dose equivalent to prednisone 5 mg

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pharmacodynamic effectiveness of different clopidogrel dosing	To assess the pharmacodynamic effectiveness of an optimised clopidogrel dosing (75 mg bid) in ET patients with documented poor responsiveness to 75 mg od.	15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of patients ET treated with standard-dose clopidogrel	To estimate the proportion of patients ET treated with standard-dose clopidogrel (75 mg once daily) who exhibit poor pharmacodynamic response to clopidogrel across	15 days
consistency over time of pharmacodynamic response	To assess the consistency over time of pharmacodynamic response in patients who are documented as good responders to clopidogrel 75 mg once daily with validated platelet function assays.	15 days

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Elena Rossi, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2026
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: June 9, 2026
• First Submitted That Met QC Criteria: June 9, 2026
• First Posted (Actual): June 12, 2026

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders; Bone Marrow Diseases; Hemorrhagic Disorders; Blood Platelet Disorders; Myeloproliferative Disorders; Hemic and Lymphatic Diseases; Thrombocytosis; Thrombocythemia, Essential
• Other Study ID Numbers: 27515

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No