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

Unstable Angina Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04718025
• Other study ID #: 2019/ABM/01/00009
• Status: Recruiting
• Phase: Phase 3
• Start date: February 7, 2022
• Est. completion date: June 30, 2024

Study information

• Verified date: April 2023
• Source: Collegium Medicum w Bydgoszczy
• Contact: Piotr Adamski, MD, PhD
• Phone: +48 52 585 4023
• Email: piotr.adamski[@]cm.umk.pl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 4500
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Angina, Unstable
• NSTEMI
• STEMI
• Unstable Angina

Intervention

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.
• Ticagrelor 60mg
Starting from day 31, LDTA and LDTP patients will receive low-dose ticagrelor 2x60mg until 12 months post-ACS.
• 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.

Locations

Country	Name	City	State
Poland	Antoni Jurasz University Hospital No. 1	Bydgoszcz

Sponsors (2)

Lead Sponsor	Collaborator
Collegium Medicum w Bydgoszczy	Medical Research Agency, Poland

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	TIMI major or minor bleeding	Composite of the first occurrence of major or minor bleeding according to the TIMI criteria.	12 months after ACS
Secondary	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
Secondary	ISTH major bleeding	The first occurrence of major bleeding according to the ISTH criteria.	12 months after ACS
Secondary	Death from any cause	Death from any cause.	12 months after ACS
Secondary	Death from cardiovascular causes	Death from cardiovascular causes.	12 months after ACS
Secondary	Myocardial infarction	Occurrence of myocardial infarction.	12 months after ACS
Secondary	Ischemic stroke	Occurrence of ischemic stroke.	12 months after ACS
Secondary	Definite or probable stent thrombosis	Occurrence of definite or probable stent thrombosis	12 months after ACS
Secondary	Dyspnea	Occurrence of dyspnea	12 months after ACS