Transition From Ticagrelor to Clopidogrel Following Acute Coronary Syndrome: To Bolus or Not?

Study Overview
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Brief Summary
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After a heart attack patients are routinely started on drugs to inhibit platelets. Ticagrelor is a powerful anti-platelet drug with clinical benefits. However it must be discontinued in some, because of increased risk of bleeding or intolerance. These patients need to be transitioned to another agent, such as Clopidogrel. At present, there is no clinical consensus on the optimal strategy for this switch. Some clinicians elect to give a bolus dose of clopidogrel with 600mg, while others start directly with a 75mg daily dose, with no evidence regarding the benefits or potential complications associated with each strategy. The present proposal will evaluate the pharmacodynamics of 2 strategies with specialized platelet function testing. We hypothesize that a bolus dose of clopidogrel during the switch will confer better ischemic protection without increasing bleeding risk for patients undergoing a switch in therapy.

Detailed Description
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The overall objective is to evaluate the need for a clopidogrel bolus dose among patients being switched from a regimen of ticagrelor to clopidogrel. In a randomized pharmacodynamics study of 48 patients, we will conduct serial measurements of platelet function/inhibition using the Accumetrics Verifynow assay (platelet inhibition will be expressed as P2Y12 reaction unit [PRU]). Platelet inhibition will be assessed at specific time points over the first 72 hours following the change in medications, which will enable us to determine whether patients in the 2 different strategies may be at increased ischemic or bleeding risks. We hypothesize that a bolus dose of clopidogrel during the switch will confer better ischemic protection without increasing bleeding risk for patients undergoing a switch in therapy. SPECIFIC AIMS: Primary Aim: To determine with platelet function testing the pharmacodynamics effects of a 600mg bolus dose of clopidogrel compared with no bolusing among patients being switched from ticagrelor to clopidogrel. To determine if patients receiving a clopidogrel bolus have improvement in ischemic protection relative to patients without a bolus dose. To determine if patients receiving a clopidogrel bolus may be exposed to increase bleeding risk relative to those without a bolus dose.

Official Title
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Transition From Ticagrelor to Clopidogrel Following Acute Coronary Syndrome: To Bolus or Not? The CAPITAL OPTI-CROSS Study.

Conditions
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Acute Coronary Syndrome

Intervention / Treatment
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* Drug: Clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age > 18, admission for acute coronary syndrome, on dual anti-platelet therapy (including ticagrelor) Being transitioned to clopidogrel by their treating physician provided informed consent Exclusion Criteria: Bleeding/intolerance to clopidogrel Thrombocytopenia (platelet count < 100, 000 per uL) Hematocrit <30% or >52% treatment with glycoprotein IIb/IIIa inhibitor, 24 hours prior to randomization

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bolus<br>Patients randomized to this arm will receive a 600mg bolus dose of clopidogrel at the time of switching from ticagrelor to clopidogrel, followed by 75mg daily. | Drug: Clopidogrel<br>* Patients on ticagrelor following an acute coronary syndrome, being transitioned to clopidogrel will be randomized to either a one time 600mg bolous dose of clopidogrel followed by 75mg daily or just starting at 75mg daily without a bolous dose.<br>* Other names: Plavix;|
| Experimental: no bolus<br>Individuals randomized to this arm will receive 75mg of clopidogrel at the time of the transition followed by a daily dose of 75mg orally. | Drug: Clopidogrel<br>* Patients on ticagrelor following an acute coronary syndrome, being transitioned to clopidogrel will be randomized to either a one time 600mg bolous dose of clopidogrel followed by 75mg daily or just starting at 75mg daily without a bolous dose.<br>* Other names: Plavix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet inhibition as assessed by P2Y12 reaction Unit (PRU) after transition from Ticagrelor to Clopidogrel. | Post randomization, blood samples at scheduled time points will be collected. Samples would enable measurement of platelet inhibition using the VerifyNow P2Y12 assay. Blood samples will be collected at baseline (prior to clopidogrel dose), 12, 24, 48, 54, 60 and 72 hours post initiation of therapy. The primary endpoint is the difference in platelet inhibition between our 2 different groups (bolus vs no bolus), as measured by P2Y12 reaction unit (PRU) using the VerifyNow assay. The PRUs have now been widely used and accepted as a measure of platelet function in the research setting. PRU will be collected at the above mentioned time points. The primary outcome will be platelet function expressed as PRUs as a continuous variable over the 72 hour time period and compared between the 2 groups. | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference in platelet inhibition (as expresses as PRU) between the two groups at specified time points. | In the secondary outcome mean platelet inhibition as measured by PRU will be compared at each specified time point between the the 2 groups. | 72 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ticagrelor, Acute coronary syndrome, Coronary artery disease, Antiplatelet therapy, Clopidogrel