PROTEUS: Prasugrel Or Ticagrelor De-escalation in NSTE-ACS

Sponsor

Collegium Medicum w Bydgoszczy (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05779059

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.4

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Non ST Segment Elevation Acute Coronary Syndrome Non-ST-Segment Elevation Myocardial Infarction (NSTEMI) Unstable Angina	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	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Apr 1, 2023

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Cardiology, Dr. A. Jurasz University Hospital, Collegium Medicum, Nicolaus Copernicus University	Bydgoszcz	Kujawsko-pomorskie	Poland	85-094