Clinical trial NCT01642238: Antithrombotic Effects of Ticagrelor Versus Clopidogrel
Official title: Randomized, Crossover Study of the Antithrombotic Effects of Ticagrelor Plus Aspirin Versus Clopidogrel Plus Aspirin When Administered With Bivalirudin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Coronary Syndrome
Keywords: Antiplatelet
ticagrelor
clopidogrel
bivalirudin
thrombosis
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2012-07-17
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether treatment with ticagrelor (plus aspirin and bivalirudin) is more effective than treatment with clopidogrel (plus aspirin and bivalirudin).

Detailed description: The HORIZONS-AMI Trial compared the effectiveness of heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) versus bivalirudin in acute myocardial infarction (AMI) patients undergoing stent deployment 1. Overall the data showed benefits associated with the bivalirudin treatment with lower rates of all-cause mortality, cardiac mortality, re-infarction and non-CABG related major bleeding; However, the data seems to indicate a non-significant increase in acute stent thrombosis in the bivalirudin group. This observation seems to suggest the potential benefits of adding an antiplatelet agent to bivalirudin. A study by Dangas G et al found that in the HORIZONS-AMI patients, the group receiving 600 mg loading-dose of clopidogrel had significantly lower 30-day unadjusted rates of mortality, reinfarction and stent thrombosis than the 300 mg loading-dose group, without increase in bleeding rate. Furthermore, even though the benefits of bivalirudin were independent of the clopidogrel loading dose; the 600mg LD was associated with more benefits with both anticoagulation regimens. Similar observations have been reported in the ARMYDA-6 MI study.

It is our hypothesis that using ticagrelor instead of clopidogrel, given its more potent and faster activity, would have greater antithrombotic activity and therefore may reduce the rate of acute stent thrombosis when administered in combination with bivalirudin + ASA in AMI patients. To investigate this hypothesis, we will compare the antithrombotic effects of ticagrelor with clopidogrel, when administered in combination with ASA and bivalirudin, in healthy human volunteers using a cross-over study design. The antithrombotic activity will be assessed pre-treatment and 2-hours and 24-hours post treatment, using methodologies including Badimon Perfusion chamber, VerifyNow P2Y12 assay, platelet aggregation with Multiplate Analyzer and Thromboelastography.

Eligibility criteria: Inclusion Criteria:

* Male or female volunteers between 18 and 65 years old.
* Body mass index (BMI) 18 - 30 kg/m2 inclusive.
* Healthy as assessed by a detailed medical history and physical examination.
* Laboratory est results within the normal range.
* Ability to provide signed informed consent.

Exclusion Criteria:

* History of clinically relevant disease, bleeding, acute infectious disease or signs of acute illness.
* Allergy or hypersensitivity to aspirin or thienopyridines, or atopy diagnosed by a physician.
* Use of medication within one month prior to study drug administration.
* History of drug abuse or alcohol consumption \>20 g/day.
* Inability to abstain from intensive muscular effort or sport competition.
* Loss of \>400 mL blood or blood donation within 3 months.
* Positive serology for hepatitis B (HBs Ag) or hepatitis C.
* Conditions associated with hemorrhagic risk.
* Positive pregnancy test.

Primary outcomes:
measure: Platelet-thrombus Formation in an ex Vivo Model of Thrombosis
timeFrame: Pre-treatment baseline and 1 hour
measure: Platelet-thrombus Formation in an ex Vivo Model of Thrombosis
timeFrame: Pre-treatment baseline and 24 hrs post treatment
Secondary outcomes:
measure: Platelet Reactivity
timeFrame: Pre-treatment baseline
measure: Platelet Reactivity
timeFrame: 1 hr post-treatment
measure: Platelet Reactivity
timeFrame: 24-hours post-treatment
measure: Blood Thrombogenicity
timeFrame: Pre-treatment baseline
measure: Blood Thrombogenicity
timeFrame: 1 hr post-treatment
measure: Blood Thrombogenicity
timeFrame: 24-hours post-treatment
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Juan J Badimon, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zafar MU, Vorchheimer DA, Tewar MP, Giannarelli C, Crippa M, Sartori S, Rodriguez D, Baber U, Mehran R, Badimon JJ. Ticagrelor reduces thrombus formation more than clopidogrel, even when co-administered with bivalirudin. Thromb Haemost. 2014 Nov;112(5):1069-70. doi: 10.1160/TH14-03-0269. Epub 2014 Aug 7. No abstract available.