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

Acute Coronary Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02054663
• Other study ID #: 20130605-01H
• Status: Completed
• Phase: Phase 4
• First received: January 27, 2014
• Last updated: March 28, 2015
• Start date: December 2013
• Est. completion date: February 2015

Study information

• Verified date: March 2015
• Source: Ottawa Heart Institute Research Corporation
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Syndrome

Intervention

Drug:
• Clopidogrel
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.

Locations

Country	Name	City	State
Canada	University of Ottawa Heart Institute	Ottawa	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Ottawa Heart Institute Research Corporation

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Differences in clinical outcomes between the 2 groups within 30 days post transition.	Other secondary clinical endpoints include the following.; TIMI major bleed; TIMI minor bleed; Myocardial Infarction; Stroke; Stent thrombosis; Death; patients will be contacted on day 30 via telephone and asked about any bleeding complications, need for transfusions, recurrent chest pains, hospitalizations or treatment as acute coronary syndrome (including repeat angiography). New onset neurological symptoms in keeping acute cerebral accidents or hospitalization for a cerebral accident.	30 days post transition	Yes
Primary	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	Yes
Secondary	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	Yes