Back to resultsEvaluation of Safety and Efficacy of Two Ticagrelor-based De-escalation Antiplatelet Strategies in Acute Coronary Syndrome (ELECTRA-SIRIO)
Primary Purpose
STEMI, NSTEMI, Unstable Angina
Status
Recruiting
Phase
Phase 3
Locations
Poland
Study Type
Interventional
Intervention
Ticagrelor 90mg
Ticagrelor 60mg
Aspirin
Sponsored by
About this trial
This is an interventional treatment trial for STEMI focused on measuring ticagrelor, aspirin, acute coronary syndrome
Eligibility Criteria
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:
- symptoms indicating myocardial ischaemia
- ST-segment changes on electrocardiography indicating myocardial ischaemia
- 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:
- ≥60 years of age;
- previous MI or coronary artery by-pass grafting;
- ≥50% stenosis in ≥2 coronary arteries;
- previous ischaemic stroke or transient ischaemic attack;
- ≥50% carotid stenosis or cerebral revascularisation;
- diabetes mellitus;
- peripheral artery disease;
- 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
Sites / Locations
- Antoni Jurasz University Hospital No. 1Recruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
Low-dose ticagrelor with aspirin (LDTA)
Low-dose ticagrelor with placebo (LDTP)
Standard-dose ticagrelor with aspirin (SDTA)
Arm Description
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.
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.
Patients with ACS in this arm will receive standard dual antiplatelet therapy including ticagrelor 2x90mg + aspirin 1x100mg during the whole 12 months after ACS.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
BARC type 3 or 5 bleeding
Composite of the first occurrence of type 3 or 5 bleeding according to the BARC criteria.
TIMI major or minor bleeding
Composite of the first occurrence of major or minor bleeding according to the TIMI criteria.
GUSTO moderate, severe, or life-threatening bleeding
Composite of the first occurrence of moderate, severe, or life-threatening bleeding according to the GUSTO criteria.
ISTH major bleeding
The first occurrence of major bleeding according to the ISTH criteria.
Death from any cause
Death from any cause.
Death from cardiovascular causes
Death from cardiovascular causes.
Myocardial infarction
Occurrence of myocardial infarction.
Ischemic stroke
Occurrence of ischemic stroke.
Definite or probable stent thrombosis
Occurrence of definite or probable stent thrombosis
Dyspnea
Occurrence of dyspnea
Full Information
NCT ID
NCT04718025
First Posted
January 17, 2021
Last Updated
April 20, 2023
Sponsor
Collegium Medicum w Bydgoszczy
Collaborators
Medical Research Agency, Poland
1. Study Identification
Unique Protocol Identification Number
NCT04718025
Brief Title
Evaluation of Safety and Efficacy of Two Ticagrelor-based De-escalation Antiplatelet Strategies in Acute Coronary Syndrome
Acronym
ELECTRA-SIRIO
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 7, 2022 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Collegium Medicum w Bydgoszczy
Collaborators
Medical Research Agency, Poland
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
STEMI, NSTEMI, Unstable Angina
Keywords
ticagrelor, aspirin, acute coronary syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
4500 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Low-dose ticagrelor with aspirin (LDTA)
Arm Type
Experimental
Arm Description
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.
Arm Title
Low-dose ticagrelor with placebo (LDTP)
Arm Type
Experimental
Arm Description
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.
Arm Title
Standard-dose ticagrelor with aspirin (SDTA)
Arm Type
Active Comparator
Arm Description
Patients with ACS in this arm will receive standard dual antiplatelet therapy including ticagrelor 2x90mg + aspirin 1x100mg during the whole 12 months after ACS.
Intervention Type
Drug
Intervention Name(s)
Ticagrelor 90mg
Other Intervention Name(s)
Brilique
Intervention Description
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
Intervention Name(s)
Ticagrelor 60mg
Other Intervention Name(s)
Brilique
Intervention Description
Starting from day 31, LDTA and LDTP patients will receive low-dose ticagrelor 2x60mg until 12 months post-ACS.
Intervention Type
Drug
Intervention Name(s)
Aspirin
Other Intervention Name(s)
acetylsalicylic acid
Intervention Description
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.
Primary Outcome Measure Information:
Title
BARC type 2, 3 or 5 bleeding
Description
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.
Time Frame
12 months after ACS
Title
Death from any cause, nonfatal MI or nonfatal stroke.
Description
The primary efficacy end point is the composite of death from any cause, first nonfatal MI, or first nonfatal stroke.
Time Frame
12 months after ACS
Secondary Outcome Measure Information:
Title
Death from any cause, nonfatal MI, nonfatal stroke, BARC type 2, 3, or 5 bleeding.
Description
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.
Time Frame
12 months after ACS
Title
BARC type 3 or 5 bleeding
Description
Composite of the first occurrence of type 3 or 5 bleeding according to the BARC criteria.
Time Frame
12 months after ACS
Title
TIMI major or minor bleeding
Description
Composite of the first occurrence of major or minor bleeding according to the TIMI criteria.
Time Frame
12 months after ACS
Title
GUSTO moderate, severe, or life-threatening bleeding
Description
Composite of the first occurrence of moderate, severe, or life-threatening bleeding according to the GUSTO criteria.
Time Frame
12 months after ACS
Title
ISTH major bleeding
Description
The first occurrence of major bleeding according to the ISTH criteria.
Time Frame
12 months after ACS
Title
Death from any cause
Description
Death from any cause.
Time Frame
12 months after ACS
Title
Death from cardiovascular causes
Description
Death from cardiovascular causes.
Time Frame
12 months after ACS
Title
Myocardial infarction
Description
Occurrence of myocardial infarction.
Time Frame
12 months after ACS
Title
Ischemic stroke
Description
Occurrence of ischemic stroke.
Time Frame
12 months after ACS
Title
Definite or probable stent thrombosis
Description
Occurrence of definite or probable stent thrombosis
Time Frame
12 months after ACS
Title
Dyspnea
Description
Occurrence of dyspnea
Time Frame
12 months after ACS
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
symptoms indicating myocardial ischaemia
ST-segment changes on electrocardiography indicating myocardial ischaemia
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:
≥60 years of age;
previous MI or coronary artery by-pass grafting;
≥50% stenosis in ≥2 coronary arteries;
previous ischaemic stroke or transient ischaemic attack;
≥50% carotid stenosis or cerebral revascularisation;
diabetes mellitus;
peripheral artery disease;
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Piotr Adamski, MD, PhD
Phone
+48 52 585 4023
Email
piotr.adamski@cm.umk.pl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacek Kubica, MD, PhD
Organizational Affiliation
Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Eliano Navarese, MD, PhD
Organizational Affiliation
Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
Official's Role
Principal Investigator
Facility Information:
Facility Name
Antoni Jurasz University Hospital No. 1
City
Bydgoszcz
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Piotr Adamski, MD, PhD
Phone
+48 585 4023
Email
piotr.adamski@cm.umk.pl
12. IPD Sharing Statement
Citations:
PubMed Identifier
34096012
Citation
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.
Results Reference
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Evaluation of Safety and Efficacy of Two Ticagrelor-based De-escalation Antiplatelet Strategies in Acute Coronary Syndrome
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