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

Evaluation of Safety and Efficacy of Two Ticagrelor-based De-escalation Antiplatelet Strategies in Acute Coronary Syndrome: the Randomized, Multicenter, Double-blind ELECTRA RCT Study

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.

Study Overview

• Status: Recruiting
• Conditions: Unstable Angina; STEMI; NSTEMI
• Intervention / Treatment: Drug: Ticagrelor 60mg; Drug: Aspirin; Drug: Ticagrelor 90mg

• Study Type: Interventional
• Enrollment (Anticipated): 4500
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Piotr Adamski, MD, PhD; Phone Number: +48 52 585 4023; Email: piotr.adamski@cm.umk.pl

Study Locations

• Poland
  • Bydgoszcz, Poland
    • Recruiting
    • Antoni Jurasz University Hospital No. 1
    • Contact: Piotr Adamski, MD, PhD; Phone Number: +48 585 4023; Email: piotr.adamski@cm.umk.pl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• diagnosis of STEMI or NSTEMI or unstable angina
• for patients with STEMI, the following three inclusion criteria will have to be met: 1) new ST-elevation at the J-point in two contiguous leads with the cut-point ≥1 mm in all leads other than leads V2-V3, where the following cut-points apply: ≥2mm in men ≥40 years; ≥2.5 mm in men <40 years, or ≥1.5 mm in women regardless of age; or a new left bundle-branch block 2) the intention to perform primary PCI 3) detection of a rise and/or fall of cardiac troponin values with at least one value above the 99th percentile upper reference limit

• 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:
  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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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: ticagrelor 2x90mg + aspirin 1x100mg during the first 30 days after ACS;; ticagrelor 2x60mg + aspirin 1x100mg starting from day 31 until 12 months after ACS.	Drug: Ticagrelor 60mg; Starting from day 31, LDTA and LDTP patients will receive low-dose ticagrelor 2x60mg until 12 months post-ACS.; Other Names: Brilique; 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.; Other Names: acetylsalicylic acid
Experimental: 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: ticagrelor 2x90mg + aspirin 1x100mg during the first 30 days after ACS;; ticagrelor 2x60mg + aspirin 1x100mg starting from day 31 until day 90 after ACS;; ticagrelor 2x60mg + placebo starting from day 91 until 12 months after ACS.	Drug: Ticagrelor 60mg; Starting from day 31, LDTA and LDTP patients will receive low-dose ticagrelor 2x60mg until 12 months post-ACS.; Other Names: Brilique
Active Comparator: 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.	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.; Other Names: acetylsalicylic acid; Drug: 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.; Other Names: Brilique

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BARC type 2, 3 or 5 bleeding	The primary safety composite end point of this study is the first occurrence of type 2, 3 or 5 bleeding according to the BARC criteria, occurring during the first 12 months after ACS.	12 months after ACS
Death from any cause, nonfatal MI or nonfatal stroke.	The primary efficacy end point is the composite of death from any cause, first nonfatal MI, or first nonfatal stroke.	12 months after ACS

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death from any cause, nonfatal MI, nonfatal stroke, BARC type 2, 3, or 5 bleeding.	The key secondary endpoint, net clinical effect, was defined as composite of death from any cause, nonfatal MI, or nonfatal stroke, and the first occurrence of BARC type 2, 3, or 5 bleeding.	12 months after ACS
BARC type 3 or 5 bleeding	Composite of the first occurrence of type 3 or 5 bleeding according to the BARC criteria.	12 months after ACS
TIMI major or minor bleeding	Composite of the first occurrence of major or minor bleeding according to the TIMI criteria.	12 months after ACS
GUSTO moderate, severe, or life-threatening bleeding	Composite of the first occurrence of moderate, severe, or life-threatening bleeding according to the GUSTO criteria.	12 months after ACS
ISTH major bleeding	The first occurrence of major bleeding according to the ISTH criteria.	12 months after ACS
Death from any cause	Death from any cause.	12 months after ACS
Death from cardiovascular causes	Death from cardiovascular causes.	12 months after ACS
Myocardial infarction	Occurrence of myocardial infarction.	12 months after ACS
Ischemic stroke	Occurrence of ischemic stroke.	12 months after ACS
Definite or probable stent thrombosis	Occurrence of definite or probable stent thrombosis	12 months after ACS
Dyspnea	Occurrence of dyspnea	12 months after ACS

Collaborators and Investigators

• Sponsor: Collegium Medicum w Bydgoszczy
• Collaborators: Medical Research Agency, Poland
• Investigators: Principal Investigator: Jacek Kubica, MD, PhD, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland; Principal Investigator: Eliano Navarese, Md, PhD, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2022
• Primary Completion (Anticipated): June 30, 2024
• Study Completion (Anticipated): June 30, 2024

Study Registration Dates

• First Submitted: January 17, 2021
• First Submitted That Met QC Criteria: January 17, 2021
• First Posted (Actual): January 22, 2021

Study Record Updates

• Last Update Posted (Actual): April 21, 2023
• Last Update Submitted That Met QC Criteria: April 20, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: acute coronary syndrome; ticagrelor; aspirin
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Angina Pectoris; Acute Coronary Syndrome; Angina, Unstable; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Ticagrelor
• Other Study ID Numbers: 2019/ABM/01/00009

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