Clinical trial NCT04718025: Evaluation of Safety and Efficacy of Two Ticagrelor-based De-escalation Antiplatelet Strategies in Acute Coronary Syndrome
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
Overall status: UNKNOWN
Phase: PHASE3
Conditions: STEMI
NSTEMI
Unstable Angina
Keywords: ticagrelor
aspirin
acute coronary syndrome
Lead sponsor: Collegium Medicum w Bydgoszczy
Sponsor class: OTHER
Collaborators: name: Medical Research Agency, Poland
First posted: 2021-01-22
Enrollment: 4500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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:

  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

Primary outcomes:
measure: BARC type 2, 3 or 5 bleeding
timeFrame: 12 months after ACS
measure: Death from any cause, nonfatal MI or nonfatal stroke.
timeFrame: 12 months after ACS
Secondary outcomes:
measure: Death from any cause, nonfatal MI, nonfatal stroke, BARC type 2, 3, or 5 bleeding.
timeFrame: 12 months after ACS
measure: BARC type 3 or 5 bleeding
timeFrame: 12 months after ACS
measure: TIMI major or minor bleeding
timeFrame: 12 months after ACS
measure: GUSTO moderate, severe, or life-threatening bleeding
timeFrame: 12 months after ACS
measure: ISTH major bleeding
timeFrame: 12 months after ACS
measure: Death from any cause
timeFrame: 12 months after ACS
measure: Death from cardiovascular causes
timeFrame: 12 months after ACS
measure: Myocardial infarction
timeFrame: 12 months after ACS
measure: Ischemic stroke
timeFrame: 12 months after ACS
measure: Definite or probable stent thrombosis
timeFrame: 12 months after ACS
measure: Dyspnea
timeFrame: 12 months after ACS
Other outcomes:
Locations:
city: Bydgoszcz
country: Poland
facility: Antoni Jurasz University Hospital No. 1
Study officials:
affiliation: Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
name: Jacek Kubica, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
name: Eliano Navarese, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.