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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Drug: Clopidogrel

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4W7
      • University of Ottawa Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bolus; 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; 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.; Other Names: Plavix
Experimental: no bolus; 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; 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.; Other Names: Plavix

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Ottawa Heart Institute Research Corporation

Publications and helpful links

General Publications

• Pourdjabbar A, Hibbert B, Chong AY, Le May MR, Labinaz M, Simard T, Ramirez FD, Lugomirski P, Maze R, Froeschl M, Glover C, Dick A, Marquis JF, Bernick J, Wells G, So DY; CAPITAL Investigators. A randomised study for optimising crossover from ticagrelor to clopidogrel in patients with acute coronary syndrome. The CAPITAL OPTI-CROSS Study. Thromb Haemost. 2017 Jan 26;117(2):303-310. doi: 10.1160/TH16-04-0340. Epub 2016 Oct 20.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: January 27, 2014
• First Submitted That Met QC Criteria: January 31, 2014
• First Posted (Estimate): February 4, 2014

Study Record Updates

• Last Update Posted (Estimate): March 31, 2015
• Last Update Submitted That Met QC Criteria: March 28, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Ticagrelor; Coronary artery disease; Acute coronary syndrome; Clopidogrel; Antiplatelet therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Syndrome; Acute Coronary Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel
• Other Study ID Numbers: 20130605-01H