Aspirin Impact on Platelet Reactivity in Acute Coronary Syndrome Patients on Novel P2Y12 Inhibitors Therapy

Phase 4

Completed

• Conditions: Acute Coronary Syndrome; Platelet Function and Reactivity Tests; Novel P2Y12 Inhibitors
• Interventions: Drug: Aspirin

• Registration Number: NCT02049762
• Lead Sponsor: Sheba Medical Center

Brief Summary

Thus far, no study has evaluated the impact on aspirin in addition to the newer and more potent P2Y12 inhibitors, among ACS patients and current guidelines recommend dual anti-platelet therapy consisting of aspirin and a novel P2Y12 inhibitor in this population.

Objective The investigators goal is to examine the effect of aspirin in addition to new anti-platelet agent (ticagrelor\\prasugrel) on platelet reactivity in comparison with placebo, among ACS patients treated percutaneously.

Design The proposed study is a randomized-controlled, double blind trial, conducted among ACS patients treated percutaneously. Eligible patients will recruited during hospitalization due to ACS after percutaneous coronary intervention (PCI), and randomization by envelopes on 1:1 basis will take place a month after the index event, at a follow-up visit at the cardiac clinic.

Platelet function and Endothelial function tests will be taken a month after the index event, and at a 2 weeks periods following aspirin/placebo therapy, cross-over and return to open-label aspirin.

End-points platelet function tests will be compared between aspirin and placebo therapy and before and after the cross-over.

Detailed Description

Introduction:

Current knowledge and data support the use of dual anti-platelets for patients after acute coronary syndrome (ACS). Novel P2Y12 inhibitors have shown their superiority on clopidogrel in regarding morbidity and mortality, but at the cost of higher bleeding rates - even in lower doses of aspirin there is increase risk for gastrointestinal (GI) bleeding. In a geographical analysis of the PLATO trial it has been shown difference at outcome. When higher dose of aspirin were used, the superiority of ticagrelor was reduced.

The use of platelet reactivity tests have been proved and acknowledged in their usefulness for gauging bleeding and ischemic risks. Few studies have shown that clopidogral is inhibiting not only the ADP activity, but also the arachidonic acid (AA) pathway that is considered aspirin specific pathway. Examining the effect of potent P2Y12 inhibitors in healthy volunteers have shown increased inhibition of the AA pathway. Not only that the adding of aspirin, have shown little effect on inhibition of AA pathway.

It has been demonstrated that vascular endothelial function is inversely correlated to platelet reactivity in both individuals without established cardiovascular disease (controls) and acute myocardial infarction patients.

Objective Our goal is to examine the effect (platelet function test and endothelial function) of aspirin while added to novel P2Y12 inhibitors treated ACS patients.

Design The proposed study is a randomized-controlled, double blind trial, conducted among ACS patients treated percutaneously. Eligible patients will recruited during hospitalization due to ACS after percutaneous coronary intervention (PCI), and randomization by envelopes on 1:1 basis will take place a month after the index event, at a follow-up visit at the cardiac clinic.

Platelet function and Endothelial function tests will be taken a month after the index event, and at a 2 weeks periods following aspirin/placebo therapy, cross-over and return to open-label aspirin.

Study end-points The primary end-point is platelet function tests in response to AA. Secondary end-points will include endothelial function and platelet reactivity according to the platelet activity and VerifyNow test in response to ADP and platelet activation Clinical outcomes including all-cause and cardiac mortality and hospitalizations, recurrent ischemia and stent thrombosis, and bleeding events along with blood transfusions, will be recorded as safety end-points.

Study Timeline

• Study First Submitted: 2014-01-28
• Study First Submitted QC: 2014-01-29
• Study First Posted: 2014-01-30
• Study Start: 2015-06
• Primary Completion: 2017-01
• Study Completion: 2017-01
• Status Verified: 2018-02
• Last Update Submitted: 2018-02-19
• Last Update Posted: 2018-02-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

• Age>18 years
• ACS defined according to the 3rd universal definition of MI
• PCI therapy

Exclusion Criteria

• Indication for anticoagulant therapy
• ACS on new P2Y12 inhibitors treatment
• Contraindication to P2Y12 therapy
• Renal failure defined as creatinine ≥1.5 mg/dL
• Non-compliance
• Life-threatening extra-cardiac disease or malignancy with a life expectancy below 1 year
• Inability to sign an informed consent
• Participation in another trial during the previous 6 months

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
P2Y12 inhibitors and placebo	Aspirin	ACS patients on novel P2Y12 inhibitors and placebo
P2Y12 inhibitors and aspirin	Aspirin	ACS patients on novel P2Y12 inhibitors and aspirin

Primary Outcome Measures

Name	Time	Method
Platelet reactivity	one month	platelet reactivity in response to arachidonic acid

Secondary Outcome Measures

Name	Time	Method
platelet reactivity	one month	platelet reactivity in response to ADP

Trial Locations

Locations (1)

Sheba Medical Center; 🇮🇱 Tel-Hashomer, Israel