Clinical trial NCT02054663: Transition From Ticagrelor to Clopidogrel Following Acute Coronary Syndrome: To Bolus or Not?
Official title: Transition From Ticagrelor to Clopidogrel Following Acute Coronary Syndrome: To Bolus or Not? The CAPITAL OPTI-CROSS Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Coronary Syndrome
Keywords: Acute coronary syndrome
Coronary artery disease
Antiplatelet therapy
Ticagrelor
Clopidogrel
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
First posted: 2014-02-04
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Platelet inhibition as assessed by P2Y12 reaction Unit (PRU) after transition from Ticagrelor to Clopidogrel.
timeFrame: 72 hours
Secondary outcomes:
measure: The difference in platelet inhibition (as expresses as PRU) between the two groups at specified time points.
timeFrame: 72 hours
Other outcomes:
measure: Differences in clinical outcomes between the 2 groups within 30 days post transition.
timeFrame: 30 days post transition
Locations:
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
Study officials:
affiliation: Ottawa Heart Institute Research Corporation
name: Derek So, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.