Prasugrel Or Ticagrelor De-escalation in NSTE-ACS (PROTEUS)

Prasugrel Or Ticagrelor De-escalation in Non-ST-elevation Acute Coronary Syndrome

The PROTEUS study is a randomized, cross-over, open-label, pharmacodynamic trial designed to compare the antiplatelet effect of reduced maintenance doses of prasugrel and ticagrelor in stable patients who recently had non-ST-elevation acute coronary syndrome (non-ST-elevation myocardial infarction or unstable angina).

Study Overview

• Status: Not yet recruiting
• Conditions: Unstable Angina; Non ST Segment Elevation Acute Coronary Syndrome; Non-ST-Segment Elevation Myocardial Infarction (NSTEMI)
• Intervention / Treatment: Drug: De-escalation to ticagrelor 60 mg at day 30; Drug: Switch to prasugrel 5 mg at day 45; Drug: De-escalation to prasugrel 5 mg at day 30; Drug: Switch to ticagrelor 60 mg at day 45

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Piotr Adamski, MD, PhD; Phone Number: +48 52 585 40 23; Email: piotr.adamski@cm.umk.pl

Study Locations

• Poland
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-094
      • Department of Cardiology, Dr. A. Jurasz University Hospital, Collegium Medicum, Nicolaus Copernicus University
      • Contact: Piotr Adamski, MD, PhD; Phone Number: +48525854023; Email: piotr.adamski@cm.umk.pl

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

Description

Inclusion Criteria:

• provision of informed consent prior to any study specific procedures
• diagnosis of non-ST-segment elevation acute coronary syndrome (non-ST-segment elevation myocardial treatment or unstable angina)
• male or non-pregnant female, aged 18-75 years old

Exclusion Criteria:

• known hypersensitivity to ticagrelor or prasugrel
• presence of contraindications for ticagrelor or prasugrel
• current treatment with oral anticoagulant or chronic therapy with low-molecular-weight heparin
• 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
• 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?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Initial ticagrelor; All patients will receive standard 180 mg loading dose of ticagrelor, followed by a standard maintenance dose of 90 mg bid for 30 days, after which de-escalation to 60 mg bid will take place and this dosing will be maintained for 15 days. At day 45 all patients will be loaded with standard 60 mg dose of prasugrel followed by reduced maintenance dose of 5 mg qd for 15 days. At day 60 all patients will be switched back to guideline recommended antiplatelet therapy.	Drug: De-escalation to ticagrelor 60 mg at day 30; Change of P2Y12 receptor antagonist regimen to ticagrelor 60 mg bid at day 30.; Drug: Switch to prasugrel 5 mg at day 45; Switch to prasugrel 5 mg qd at day 45.
Experimental: Initial prasugrel; All patients will receive standard 60 mg loading dose of prasugrel, followed by a standard maintenance dose 10 mg qd for 30 days, after which de-escalation to 5 mg qd will take place and this dosing will be maintained for 15 days. At day 45 patients will be loaded with standard 180 mg dose of ticagrelor followed by reduced maintenance dose of 60 mg bid for 15 days. At day 60 all patients will be switched back to guideline recommended antiplatelet therapy.	Drug: De-escalation to prasugrel 5 mg at day 30; Change of P2Y12 receptor antagonist regimen to prasugrel 5 mg qd at day 30.; Drug: Switch to ticagrelor 60 mg at day 45; Switch to ticagrelor 60 mg bid at day 45.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet Reactivity Assessed with Multiple Electrode Aggregometry	Platelet Reactivity Assessed with Multiple Electrode Aggregometry will be evaluated after 15 days of using reduced maintenance dose of prasugrel or ticagrelor.	day 15 of using reduced maintenance dose of prasugrel or ticagrelor

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet Reactivity Assessed with the VerifyNow assay	Platelet Reactivity Assessed with the VerifyNow assay will be evaluated after 15 days of using reduced maintenance dose of prasugrel or ticagrelor.	day 15 of using reduced maintenance dose of prasugrel or ticagrelor
High Platelet Reactivity according to Multiple Electrode Aggregometry	Percentage of Patients With High Platelet Reactivity according to Multiple Electrode Aggregometry after 15 days of using reduced maintenance dose of prasugrel or ticagrelor.	day 15 of using reduced maintenance dose of prasugrel or ticagrelor
High Platelet Reactivity according to the VerifyNow assay	Percentage of Patients With High Platelet Reactivity according to the VerifyNow assay after 15 days of using reduced maintenance dose of prasugrel or ticagrelor.	day 15 of using reduced maintenance dose of prasugrel or ticagrelor

Collaborators and Investigators

• Sponsor: Collegium Medicum w Bydgoszczy
• Investigators: Principal Investigator: Piotr Adamski, MD, PhD, CM UMK

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2023
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: March 9, 2023
• First Submitted That Met QC Criteria: March 9, 2023
• First Posted (Actual): March 22, 2023

Study Record Updates

• Last Update Posted (Actual): March 22, 2023
• Last Update Submitted That Met QC Criteria: March 9, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: acute coronary syndrome; prasugrel; ticagrelor; de-escalation
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Disease; Chest Pain; Angina Pectoris; Myocardial Infarction; Infarction; Syndrome; Acute Coronary Syndrome; Angina, Unstable; 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: 2023/01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No