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

University of Ottawa Heart Institute

Status and phase: Completed; Phase 4

Conditions: Acute Coronary Syndrome

Treatments: Drug: Clopidogrel

Study type: Interventional

Funder types: Other

Identifiers

NCT02054663

20130605-01H

Details and patient eligibility

About

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.

Full description

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:

1. 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.
2. To determine if patients receiving a clopidogrel bolus have improvement in ischemic protection relative to patients without a bolus dose.
3. To determine if patients receiving a clopidogrel bolus may be exposed to increase bleeding risk relative to those without a bolus dose.

Enrollment: 60 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Bolus

Experimental group

Description:

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.

Treatment:

Drug: Clopidogrel

no bolus

Experimental group

Description:

Individuals randomized to this arm will receive 75mg of clopidogrel at the time of the transition followed by a daily dose of 75mg orally.

Treatment:

Drug: Clopidogrel