Daily Variability of Platelet Aggregation in Patients With Myocardial Infarction Treated With Prasugrel and Ticagrelor (DRAGON)

Comparison of Circadian Variability of Platelet Inhibition in Patients With Myocardial Infarction Treated With Prasugrel and Ticagrelor

The aim of this study is to compare circadian variability of antiplatelet effect of prasugrel and ticagrelor maintenance doses during the initial days after acute myocardial infarction.

Study Overview

• Status: Completed
• Conditions: Acute Myocardial Infarction
• Intervention / Treatment: Drug: Prasugrel; Drug: Ticagrelor

Detailed Description

Prasugrel and ticagrelor are two oral P2Y12 receptor antagonists recommended as a part of dual antiplatelet therapy with aspirin in patients with acute myocardial infarction. Both drugs exert comparable antiplatelet effect following a loading dose. However, pharmacodynamic differences exist between these P2Y12 receptor inhibitors. Prasugrel is a prodrug that requires hepatic activation and permanently binds to platelet P2Y12 receptors, whereas ticagrelor is an active drug and blocks P2Y12 receptors reversibly. Another important difference is that prasugrel maintenance dose is administered once daily, while ticagrelor requires next dosage every 12 hours. These fundamental distinctions may affect the degree of platelet inhibition on maintenance doses during the first days after acute myocardial infarction.

• Study Type: Observational
• Enrollment (Actual): 73

Contacts and Locations

Study Locations

• Poland
  • Dolnośląskie
    • Wrocław, Dolnośląskie, Poland, 50-556
      • Department of Cardiology, Wrocław Medical University
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-094
      • Department of Cardiology, Dr. A. Jurasz University Hospital, Collegium Medicum, Nicolaus Copernicus University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with acute myocardial infarction treated invasively.

Description

Inclusion Criteria:

• provision of informed consent prior to any study specific procedures
• diagnosis of acute ST-segment elevation myocardial infarction or acute non-ST-segment elevation myocardial infarction
• male or non-pregnant female, aged 18-75 years old
• provision of informed consent for angiography and percutaneous coronary intervention

Exclusion Criteria:

• treatment with ticlopidine, clopidogrel, prasugrel or ticagrelor within 14 days before the study enrollment
• hypersensitivity to ticagrelor or prasugrel
• contraindications for ticagrelor or prasugrel
• current treatment with oral anticoagulant or chronic therapy with low-molecular-weight heparin
• active bleeding
• history of ischemic stroke or transient ischemic attack
• history of intracranial hemorrhage
• recent gastrointestinal bleeding (within 30 days)
• history of moderate or severe hepatic impairment
• history of major surgery or severe trauma (within 3 months)
• patient required dialysis
• manifest infection or inflammatory state
• concomitant therapy with strong CYP3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir) or strong CYP3A inducers (rifampicin, phenytoin, carbamazepine, dexamethasone, phenobarbital) within 14 days and during study treatment
• body weight below 60 kg

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Prasugrel; Patients with myocardial infarction will receive prasugrel as a part of dual antiplatelet therapy with aspirin.	Drug: Prasugrel; Patients with myocardial infarction will receive a 60 mg prasugrel loading dose, followed by a maintenance dose of 10 mg once daily; Other Names: Efient
Ticagrelor; Patients with myocardial infarction will receive ticagrelor as a part of dual antiplatelet therapy with aspirin.	Drug: Ticagrelor; Patients with myocardial infarction will receive a 180 mg ticagrelor loading dose, followed by a maintenance dose of 90 mg twice daily; Other Names: Brilique

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Circadian variability of platelet inhibition assessed with VASP	Platelet inhibition evaluated with VASP assay at 8:00, 12:00, 16:00 and 20:00	Day 4 after acute myocardial infarction
Circadian variability of platelet inhibition assessed with Multiplate	Platelet inhibition evaluated with Multiplate at 8:00, 12:00, 16:00 and 20:00	Day 4 after acute myocardial infarction

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
High platelet reactivity at 8:00 assessed with VASP	Number of patients with high platelet reactivity evaluated with VASP assay at 8:00	Day 4 after acute myocardial infarction
High platelet reactivity at 12:00 assessed with VASP	Number of patients with high platelet reactivity evaluated with VASP assay at 12:00	Day 4 after acute myocardial infarction
High platelet reactivity 16:00 assessed with VASP	Number of patients with high platelet reactivity evaluated with VASP assay at 16:00	Day 4 after acute myocardial infarction
High platelet reactivity 20:00 assessed with VASP	Number of patients with high platelet reactivity evaluated with VASP assay at 20:00	Day 4 after acute myocardial infarction
High platelet reactivity 08:00 assessed with Multiplate	Number of patients with high platelet reactivity evaluated with Multiplate at 08:00	Day 4 after acute myocardial infarction
High platelet reactivity 12:00 assessed with Multiplate	Number of patients with high platelet reactivity evaluated with Multiplate at 12:00	Day 4 after acute myocardial infarction
High platelet reactivity 16:00 assessed with Multiplate	Number of patients with high platelet reactivity evaluated with Multiplate at 16:00	Day 4 after acute myocardial infarction
High platelet reactivity 20:00 assessed with Multiplate	Number of patients with high platelet reactivity evaluated with Multiplate at 20:00	Day 4 after acute myocardial infarction

Collaborators and Investigators

• Sponsor: Collegium Medicum w Bydgoszczy
• Investigators: Principal Investigator: Jacek Kubica, Prof., Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2018
• Primary Completion (Actual): February 28, 2019
• Study Completion (Actual): February 28, 2019

Study Registration Dates

• First Submitted: February 27, 2018
• First Submitted That Met QC Criteria: February 27, 2018
• First Posted (Actual): March 6, 2018

Study Record Updates

• Last Update Posted (Actual): February 26, 2020
• Last Update Submitted That Met QC Criteria: February 23, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: STEMI; prasugrel; ticagrelor; platelet reactivity; NSTEMI; VASP
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; 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; Prasugrel Hydrochloride
• Other Study ID Numbers: CMUMK202I

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No