Comparison of Low-Dose, Standard-Dose Ticagrelor and Clopidogrel for Inhibition of Platelet Reactivity in Patients With Acute Coronary Syndromes (OPTIMA)

Comparison of Low-Dose, Standard-Dose Ticagrelor and Clopidogrel for Inhibition of Platelet Reactivity in Patients With Acute Coronary Syndromes; Pharmacodynamics and Pharmacokinetics Study

The purpose of this study is to compare Low-Dose, Standard-Dose Ticagrelor and Clopidogrel for Inhibition of Platelet Reactivity in Patients with Acute Coronary Syndromes

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Drug: clopidogrel; Drug: ticagrelor

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Songpa-gu
    • Seoul, Songpa-gu, Korea, Republic of, 138-736
      • Asan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ST elevation or non ST elevation acute coronary syndrome patients of chest pain within 24 hours

Exclusion Criteria:

• Known hypersensitivity to clopidogrel and ticagrelor and aspirin
• Treatment with anticoagulants
• Exposure to a thrombolytic agent within 24 hours prior to randomization
• Use of glycoprotein IIb - IIIa inhibitors at randomization
• History of major hemorrhage (intracranial, gastrointestinal, etc.)
• clotting disorder and/or bleeding disorder
• Any history of Severe renal or hepatic dysfunction
• Hematologic disorder including a Hemoglobin less than 10 g/L or a platelet count less than 80,000 cells/mm3
• Cardiac shock, severe left ventricular dysfunction LVEF less than 30%
• Sick sinus syndrome or second degree of av block without permanent pacemaker
• No concurrent cytochrome p450 3a inhibitors and enhancers within 2 weeks
• Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg,drug and alcohol abuse, mental illness) or that could prevent, limit, or confound the protocol-specified assessments.
• Life expectancy of less than 6 months
• Pregnancy or lactating
• Participation in any drug study in the previous 3 months
• Inability to follow the protocol and comply with follow-up requirements or any other reason that the investigator feels would place the patient at increased risk

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low dose ticagrelor; 60mg bid	Drug: ticagrelor
Active Comparator: standard dose ticagrelor; 90mg bid	Drug: ticagrelor
Active Comparator: standard dose clopidogrel; 75mg qd	Drug: clopidogrel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
P2Y12 reaction units(PRU)	P2Y12 Reaction Units (PRU) measured by VerifyNow P2Y12 assay	8 hours and 30days after first randomized dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage inhibition of platelet aggregation		0, 0.5, 1, 2, 4, 8,24 hours and 30 days after first randomized study treatment
Aggregation units(AU), Area Under the Curve(AUC)	by Multiplate analyzer	0, 0.5, 1, 2, 4, 8,24 hours and 30 days after first randomized study treatment
Percentage of low-responsive patients	Low-responsive patients is defined as PRU ≥ 235 from VerifyNow P2Y12 and/or percentage of platelet inhibition <15%	0, 0.5, 1, 2, 4, 8,24 hours and 30 days after first randomized study treatment
Description of the pharmacokinetic (PK) profile for Ticagrelor and its metabolite AR-C124910XX	in terms of maximum concentration (Cmax),time to maximum concentration (tmax) and area under the concentration curve from time zero to infinity (AUC), t1/2, CL/F	0, 0.5, 1, 2, 4, 8, 10,24 hours after first randomized study treatment
MACE(Major adverse cardiac event)	Death, Myocardial Infarction, stent thrombosis, stroke,	30 days after first randomized study treatment
Adverse event	including bleeding by TIMI/PLATO criteria, dyspnea, bradycardia, syncope,	30 days after first randomized study treatment
Drug tolerance	Drug tolerance is evaluated as adverse event following discontinuation of drug administration	30 days after first randomized study treatment

Collaborators and Investigators

• Sponsor: Seung-Jung Park
• Collaborators: Roche Pharma AG; AstraZeneca; KBM pharm

Publications and helpful links

General Publications

• Park DW, Lee PH, Jang S, Lim HS, Kang DY, Lee CH, Ahn JM, Yun SC, Park SW, Park SJ. Effect of Low-Dose Versus Standard-Dose Ticagrelor and Clopidogrel on Platelet Inhibition in Acute Coronary Syndromes. J Am Coll Cardiol. 2018 Apr 10;71(14):1594-1595. doi: 10.1016/j.jacc.2018.02.010. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2015
• Primary Completion (Actual): February 14, 2017
• Study Completion (Actual): March 10, 2017

Study Registration Dates

• First Submitted: December 15, 2014
• First Submitted That Met QC Criteria: December 17, 2014
• First Posted (Estimate): December 18, 2014

Study Record Updates

• Last Update Posted (Actual): June 16, 2017
• Last Update Submitted That Met QC Criteria: June 15, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Pharmacokinetics; ticagrelor; clopidogrel; Pharmacodynamics; Inhibition of Platelet Reactivity
• 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; Ticagrelor; Clopidogrel
• Other Study ID Numbers: AMCCV2014-07