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

Phase 3

Recruiting

• Conditions: NSTEMI; Unstable Angina; STEMI
• Interventions: Drug: Ticagrelor 90mg; Drug: Ticagrelor 60mg; Drug: Aspirin

• Registration Number: NCT04718025
• Lead Sponsor: Collegium Medicum w Bydgoszczy

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-01-17
• Study First Submitted QC: 2021-01-17
• Study First Posted: 2021-01-22
• Study Start: 2022-02-07
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-20
• Last Update Posted: 2023-04-21
• Primary Completion: 2024-06-30
• Study Completion: 2024-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 4500

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:
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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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard-dose ticagrelor with aspirin (SDTA)	Ticagrelor 90mg	Patients with ACS in this arm will receive standard dual antiplatelet therapy including ticagrelor 2x90mg + aspirin 1x100mg during the whole 12 months after ACS.
Low-dose ticagrelor with aspirin (LDTA)	Ticagrelor 60mg	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.
Low-dose ticagrelor with placebo (LDTP)	Ticagrelor 60mg	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.
Low-dose ticagrelor with aspirin (LDTA)	Aspirin	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.
Standard-dose ticagrelor with aspirin (SDTA)	Aspirin	Patients with ACS in this arm will receive standard dual antiplatelet therapy including ticagrelor 2x90mg + aspirin 1x100mg during the whole 12 months after ACS.

Primary Outcome Measures

Name	Time	Method
BARC type 2, 3 or 5 bleeding	12 months after ACS	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.
Death from any cause, nonfatal MI or nonfatal stroke.	12 months after ACS	The primary efficacy end point is the composite of death from any cause, first nonfatal MI, or first nonfatal stroke.

Secondary Outcome Measures

Name	Time	Method
Definite or probable stent thrombosis	12 months after ACS	Occurrence of definite or probable stent thrombosis
ISTH major bleeding	12 months after ACS	The first occurrence of major bleeding according to the ISTH criteria.
Death from any cause	12 months after ACS	Death from any cause.
Death from cardiovascular causes	12 months after ACS	Death from cardiovascular causes.
Myocardial infarction	12 months after ACS	Occurrence of myocardial infarction.
Ischemic stroke	12 months after ACS	Occurrence of ischemic stroke.
Death from any cause, nonfatal MI, nonfatal stroke, BARC type 2, 3, or 5 bleeding.	12 months after ACS	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.
BARC type 3 or 5 bleeding	12 months after ACS	Composite of the first occurrence of type 3 or 5 bleeding according to the BARC criteria.
TIMI major or minor bleeding	12 months after ACS	Composite of the first occurrence of major or minor bleeding according to the TIMI criteria.
GUSTO moderate, severe, or life-threatening bleeding	12 months after ACS	Composite of the first occurrence of moderate, severe, or life-threatening bleeding according to the GUSTO criteria.
Dyspnea	12 months after ACS	Occurrence of dyspnea

Trial Locations

Locations (1)

Antoni Jurasz University Hospital No. 1; 🇵🇱 Bydgoszcz, Poland