Prasugrel Or Ticagrelor De-escalation in NSTE-ACS

Phase 3

Not yet recruiting

• Conditions: Unstable Angina; Non ST Segment Elevation Acute Coronary Syndrome; Non-ST-Segment Elevation Myocardial Infarction (NSTEMI)
• Interventions: Drug: De-escalation to ticagrelor 60 mg at day 30; Drug: De-escalation to prasugrel 5 mg at day 30; Drug: Switch to ticagrelor 60 mg at day 45; Drug: Switch to prasugrel 5 mg at day 45

• Registration Number: NCT05779059
• Lead Sponsor: Collegium Medicum w Bydgoszczy

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Status Verified: 2023-03
• Study First Submitted: 2023-03-09
• Study First Submitted QC: 2023-03-09
• Last Update Submitted: 2023-03-09
• Study First Posted: 2023-03-22
• Last Update Posted: 2023-03-22
• Study Start: 2023-04-01
• Primary Completion: 2024-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 50

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Initial ticagrelor	De-escalation to ticagrelor 60 mg at day 30	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.
Initial prasugrel	Switch to ticagrelor 60 mg at day 45	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.
Initial ticagrelor	Switch to prasugrel 5 mg at day 45	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.
Initial prasugrel	De-escalation to prasugrel 5 mg at day 30	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Department of Cardiology, Dr. A. Jurasz University Hospital, Collegium Medicum, Nicolaus Copernicus University; 🇵🇱 Bydgoszcz, Kujawsko-pomorskie, Poland