Evaluation of Safety and Efficacy of Two Ticagrelor-based De-escalation Antiplatelet Strategies in Acute Coronary Syndrome

NCT ID: NCT04718025

Last Updated: 2023-04-21

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 4500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-07
• Study Completion Date: 2024-06-30

Brief Summary

The ELECTRA-SIRIO 2 study is a randomized, multicenter, double-blind, investigator-initiated clinical trial aimed to evaluate safety and efficacy of two ticagrelor-based de-escalation antiplatelet strategies in patients with acute coronary syndrome (ACS). During the hospitalization due to ACS, participants will be randomized in a 1:1:1 ratio into one of three arms: low-dose ticagrelor with aspirin (LDTA), low-dose ticagrelor with placebo (LDTP), and standard-dose ticagrelor with aspirin (SDTA), the latter being the control arm. Up to day 30, all enrolled patients will receive standard-dose ticagrelor (2x90mg) + aspirin (1x100mg). Starting from day 31 LDTA and LDTP patients will receive low-dose ticagrelor (2x60mg) + aspirin (1x100mg), SDTA - continuation of previous treatment. Starting from day 91 LDTP patients will receive low-dose ticagrelor (2x60mg) + placebo, SDTA and LDTA - continuation of previous treatment. The aim of the study is to evaluate the influence of ticagrelor maintenance dose reduction from 2x90mg to 2x60mg with or without continuation of aspirin versus dual antiplatelet therapy with standard dose ticagrelor in reducing clinically relevant bleeding and maintaining anti-ischemic efficacy in ACS patients.

Conditions

STEMI; NSTEMI; Unstable Angina

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Low-dose ticagrelor with aspirin (LDTA)

Patients with ACS in this arm will be subject to reduction of ticagrelor maintenance dose from 2x90mg to 2x60mg after the first month post-ACS, and will receive the following antiplatelet therapy:

1. ticagrelor 2x90mg + aspirin 1x100mg during the first 30 days after ACS;

2. ticagrelor 2x60mg + aspirin 1x100mg starting from day 31 until 12 months after ACS.

Group Type: EXPERIMENTAL

Ticagrelor 60mg

Intervention Type: DRUG

Starting from day 31, LDTA and LDTP patients will receive low-dose ticagrelor 2x60mg until 12 months post-ACS.

Aspirin

Intervention Type: DRUG

Up to day 90 after ACS, all enrolled patients will receive aspirin 1x100mg as a part of dual antiplatelet therapy. Starting from day 91, LDTP patients will discontinue aspirin and proceed with low-dose ticagrelor monotherapy until 12 months post-ACS, while patients in LDTA and SDTA will continue aspirin 1x100 mg until 12 months post-ACS.

Low-dose ticagrelor with placebo (LDTP)

Patients with ACS in this arm will be subject to reduction of ticagrelor maintenance dose from 2x90mg to 2x60mg after the first month post-ACS, followed by discontinuation of aspirin after 3 months post-ACS, and will receive the following antiplatelet therapy:

1. ticagrelor 2x90mg + aspirin 1x100mg during the first 30 days after ACS;

2. ticagrelor 2x60mg + aspirin 1x100mg starting from day 31 until day 90 after ACS;

3. ticagrelor 2x60mg + placebo starting from day 91 until 12 months after ACS.

Group Type: EXPERIMENTAL

Ticagrelor 60mg

Intervention Type: DRUG

Starting from day 31, LDTA and LDTP patients will receive low-dose ticagrelor 2x60mg until 12 months post-ACS.

Standard-dose ticagrelor with aspirin (SDTA)

Patients with ACS in this arm will receive standard dual antiplatelet therapy including ticagrelor 2x90mg + aspirin 1x100mg during the whole 12 months after ACS.

Group Type: ACTIVE_COMPARATOR

Ticagrelor 90mg

Intervention Type: DRUG

Up to day 30 after ACS, all enrolled patients will receive standard-dose ticagrelor 2x90mg as a part of dual antiplatelet therapy. Participants in SDTA arm will continue treatment with ticagrelor 2x90mg until 12 months post-ACS, while patients in LDTA and LDTP will be switched to low-dose ticagrelor 2x60 mg starting on day 31.

Aspirin

Intervention Type: DRUG

Up to day 90 after ACS, all enrolled patients will receive aspirin 1x100mg as a part of dual antiplatelet therapy. Starting from day 91, LDTP patients will discontinue aspirin and proceed with low-dose ticagrelor monotherapy until 12 months post-ACS, while patients in LDTA and SDTA will continue aspirin 1x100 mg until 12 months post-ACS.

Interventions

Ticagrelor 90mg

Up to day 30 after ACS, all enrolled patients will receive standard-dose ticagrelor 2x90mg as a part of dual antiplatelet therapy. Participants in SDTA arm will continue treatment with ticagrelor 2x90mg until 12 months post-ACS, while patients in LDTA and LDTP will be switched to low-dose ticagrelor 2x60 mg starting on day 31.

Intervention Type: DRUG

Ticagrelor 60mg

Starting from day 31, LDTA and LDTP patients will receive low-dose ticagrelor 2x60mg until 12 months post-ACS.

Intervention Type: DRUG

Aspirin

Up to day 90 after ACS, all enrolled patients will receive aspirin 1x100mg as a part of dual antiplatelet therapy. Starting from day 91, LDTP patients will discontinue aspirin and proceed with low-dose ticagrelor monotherapy until 12 months post-ACS, while patients in LDTA and SDTA will continue aspirin 1x100 mg until 12 months post-ACS.

Intervention Type: DRUG

Other Intervention Names

Brilique; Brilique; acetylsalicylic acid

Eligibility Criteria

Inclusion Criteria

• diagnosis of STEMI or NSTEMI or unstable angina
• for patients with NSTEMI or unstable angina, at least two of the following three criteria will have to be met:

1. symptoms indicating myocardial ischaemia

2. ST-segment changes on electrocardiography indicating myocardial ischaemia

3. detection of a rise and/or fall of cardiac troponin values with at least one value above the 99th percentile upper reference limit in addition to at least one of the following:

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1. ≥60 years of age;

2. previous MI or coronary artery by-pass grafting;

3. ≥50% stenosis in ≥2 coronary arteries;

4. previous ischaemic stroke or transient ischaemic attack;

5. ≥50% carotid stenosis or cerebral revascularisation;

6. diabetes mellitus;

7. peripheral artery disease;

8. chronic kidney disease with glomerular filtration rate <60 mL/min.

Exclusion Criteria

• contraindications to ticagrelor or/and aspirin
• indications for oral anticoagulation therapy
• second or third grade atrio-ventricular block
• previous stent thrombosis on treatment with ticagrelor
• end stage kidney disease with glomerular filtration rate <15 mL/min or on haemodialysis
• administration of prasugrel during the index event
• pregnancy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical Research Agency, Poland

OTHER_GOV

Sponsor Role: collaborator

Collegium Medicum w Bydgoszczy

OTHER

Sponsor Role: lead

Responsible Party

Jacek Kubica

Prof. dr hab.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jacek Kubica, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland

Eliano Navarese, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland

Locations

Antoni Jurasz University Hospital No. 1

Bydgoszcz, , Poland

Site Status: RECRUITING

Countries

Poland

Central Contacts

Piotr Adamski, MD, PhD

Role: CONTACT

piotr.adamski@cm.umk.pl

+48 52 585 4023

Facility Contacts

Piotr Adamski, MD, PhD

Role: primary

piotr.adamski@cm.umk.pl

+48 585 4023

References

Kubica J, Adamski P, Niezgoda P, Kubica A, Podhajski P, Baranska M, Uminska JM, Pietrzykowski L, Ostrowska M, Siller-Matula JM, Badariene J, Bartus S, Budaj A, Dobrzycki S, Fidor L, Gasior M, Gessek J, Gierlotka M, Gil R, Goracy J, Grzelakowski P, Hajdukiewicz T, Jaguszewski M, Janion M, Kasprzak J, Kern A, Klecha A, Kleinrok A, Kochman W, Krakowiak B, Legutko J, Lesiak M, Nosal M, Piotrowski G, Przybylski A, Roleder T, Skonieczny G, Sobieszek G, Tycinska A, Wojciechowski D, Wojakowski W, Wojcik J, Zielinska M, Zurakowski A, Specchia G, Gorog DA, Navarese EP. A new approach to ticagrelor-based de-escalation of antiplatelet therapy after acute coronary syndrome. A rationale for a randomized, double-blind, placebo-controlled, investigator-initiated, multicenter clinical study. Cardiol J. 2021;28(4):607-614. doi: 10.5603/CJ.a2021.0056. Epub 2021 Jun 7.

Reference Type: DERIVED

PMID: 34096012 (View on PubMed)

Other Identifiers

2019/ABM/01/00009

Identifier Type: -

Identifier Source: org_study_id