Percutaneous Coronary Intervention Followed by Antiplatelet Monotherapy in the Setting of Acute Coronary Syndromes

Phase 3

Active, not recruiting

• Conditions: Acute Coronary Syndrome
• Interventions: Drug: Antiplatelet Monotherapy

• Registration Number: NCT04360720
• Lead Sponsor: Hospital Israelita Albert Einstein

Brief Summary

Phase-3, randomized, multicenter, parallel-group study with blind evaluation of endpoints and intention-to-treat analysis.

The general purpose of the study is evaluate the non-inferiority hypothesis for ischemic events and the superiority hypothesis for bleeding events resulting from platelet P2Y12 receptor inhibitors given as monotherapy in comparison with conventional dual antiplatelet therapy in acute coronary syndrome patients treated with percutaneous coronary intervention in the context of the Unified Health System in Brazil.

Detailed Description

Based on current scientific evidence, acute coronary syndrome subjects should be treated with dual antiplatelet therapy, which consists of the association of acetylsalicylic acid with an oral antagonist of platelet P2Y12 receptor. Clinical trials have shown that dual antiplatelet therapy reduces ischemic events, despite of increasing the risk of bleeding complications. Because dual antiplatelet therapy has a positive net effect, such an approach is currently recommended by international guidelines and recognized as the therapy of choice for acute coronary syndrome subjects. It is known that the acetylsalicylic acid dose is directly proportional to the bleeding risk. However, so far, all new antiplatelet drugs have been tested and used in association with acetylsalicylic acid for a varying period of time. This study is carried out in such context and intends to evaluate the clinical performance of new inhibitors of platelet P2Y12 receptor given solely, as monotherapy, to acute coronary syndrome patients, to test the hypothesis that an antithrombotic monotherapy with such agents (i.e., acetylsalicylic acid withdrawal) sustains efficacy by preventing ischemic complications while reducing the bleeding potential of this drug dosage regimens. It is a Phase-3, randomized, multicenter, parallel-group study with blind evaluation of endpoints and intention-to-treat analysis. Subjects with acute coronary syndrome treated with a successful percutaneous coronary intervention will be enrolled. The general purpose of the study is to test the non-inferiority hypothesis for ischemic events and the superiority hypothesis for bleeding events resulting from platelet P2Y12 receptor inhibitors given as monotherapy in comparison with conventional dual antiplatelet therapy in the context of the Unified Health System in Brazil.

Study Timeline

• Study First Submitted: 2020-04-22
• Study First Submitted QC: 2020-04-23
• Study First Posted: 2020-04-24
• Study Start: 2020-10-15
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-04
• Last Update Posted: 2025-04-08
• Primary Completion: 2025-05-30
• Study Completion: 2025-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 3400

Inclusion Criteria

Subjects must meet all the criteria below:

1. Age >=18 years;
2. Clinical presentation compatible with acute coronary syndrome with onset < 24 hours before admission;
3. Successful percutaneous coronary intervention(s) of all target lesions (culprit and non-culprit) with new-generation drug-eluting stents;
4. Length of stay in hospital at randomization < 96 hours;
5. Subjects will be informed about the nature of the study and must agree to comply and give an informed consent in writing using a form approved in advance by the local Ethics Committee.

Exclusion Criteria

Subjects meeting any of the following criteria will be excluded:

1. Acute coronary syndrome on index admission treated in a conservative way or by unsuccessful percutaneous intervention or surgically;
2. Presence of residual lesions which are likely to require future treatment in the next 12 months;
3. Fibrinolytic therapy < 24 hour before randomization;
4. Need of oral anticoagulation with warfarin or new anticoagulants;
5. Chronic bleeding diathesis;
6. Active or recent major bleeding (in-hospital);
7. Prior intracranial hemorrhage;
8. Ischemic cerebrovascular accident < 30 days;
9. Presence of brain arteriovenous malformation;
10. Index event of non-atherothrombotic etiology (i.e., stent thrombosis, coronary embolism, spontaneous coronary artery dissection, myocardial ischemia due to supply/demand imbalance);
11. Potential or scheduled cardiac or non-cardiac surgery in the next 12 months;
12. Platelet count < 100,000 cells/mm3 or > 700,000 cells/mm3;
13. Total white blood count < 3,000 cells/mm3;
14. Suspected or documented active liver disease (including laboratory evidence of hepatitis B or C);
15. Receiver of heart transplant;
16. Known allergies or intolerance of acetylsalicylic acid, clopidogrel, ticlopidine, ticagrelor, prasugrel, heparin or antiproliferative agents from the limus-family of drugs;
17. Subject with life expectation lower than 1 year;
18. Any significant medical condition that, in the investigator's opinion, could interfere with the ideal participation of the subject in the study;
19. Participation in other study in the past 12 months, unless a direct benefit to the subject can be expected.
20. Impossibility of being treated with dual antiplatelet therapy for 12 months, based on investigator judgement.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Antiplatelet Monotherapy	Antiplatelet Monotherapy	All subjects randomized to the Monotherapy Group will have acetylsalicylic acid discontinued immediately after randomization. Subjects randomized to the Monotherapy Group will be treated with ticagrelor or prasugrel alone for 12 months. Ticagrelor alone (90 mg twice daily) Or Prasugrel alone (10 mg once daily)

Primary Outcome Measures

Name	Time	Method
Bleeding Academic Research Consortium (BARC) type-2, -3 or -5 bleeding event	12 months	Co-Primary Safety Endpoint (superiority hypothesis)
Composite endpoint of all-cause mortality, cerebrovascular accident, myocardial infarction or urgent target vessel revascularization.	12 months	Co-Primary Efficacy Endpoint (non-inferiority hypothesis)

Secondary Outcome Measures

Name	Time	Method
Sudden death	30 days	Sudden death
Myocardial Infarction	12 months	Myocardial Infarction
Total of deaths, and cardiac and non-cardiac deaths	12 months	Total of deaths, and cardiac and non-cardiac deaths
Non-scheduled invasive coronary treatment	12 months	Non-scheduled invasive coronary treatment
BARC 1-5 type bleeding	12 months	BARC 1-5 type bleeding
Stent thrombosis	12 months	Stent thrombosis
Composite net adverse event (occurrence of co-primary efficacy endpoint or co-primary safety endpoint)	12 months	Composite net adverse event (occurrence of co-primary efficacy endpoint or co-primary safety endpoint)
Cost-effectiveness ratio	12 months	Cost-effectiveness ratio
Cerebrovascular accident	12 months	Cerebrovascular accident

Trial Locations

Locations (49)

Hospital de Clínicas de Porto Alegre; 🇧🇷 Porto Alegre, RS, Brazil

Acurácia Serviços Médicos; 🇧🇷 Rio Branco, Acre, Brazil

Hospital Ana Nery; 🇧🇷 Salvador, BA, Brazil

Hospital de Messejana Dr. Carlos Alberto Studart Gomes; 🇧🇷 Fortaleza, CE, Brazil

Hospital de Base de Brasília; 🇧🇷 Brasília, DF, Brazil

Instituto Aramari APO; 🇧🇷 Brasília, DF, Brazil

Instituto Cardiovascular de Linhares; 🇧🇷 Linhares, ES, Brazil

Hospital Evangélico de Vila Velha; 🇧🇷 Vila Velha, ES, Brazil

Hospital Santa Casa de Misericórdia de Vitória; 🇧🇷 Vitória, ES, Brazil

Universidade Federal de Goiás; 🇧🇷 Goiânia, GO, Brazil

CASSEMS; 🇧🇷 Campo Grande, Mato Grosso Do Sul, Brazil

Hospital Felício Rocho; 🇧🇷 Belo Horizonte, MG, Brazil

Instituto Nacional de Cardiologia - INC; 🇧🇷 Rio De Janeiro, RJ, Brazil

Hospital Madre Teresa; 🇧🇷 Belo Horizonte, MG, Brazil

Hospital Universitário Ciências Médicas de Belo Horizonte; 🇧🇷 Belo Horizonte, MG, Brazil

Hospital Santa Lucia; 🇧🇷 Poços De Caldas, MG, Brazil

Hospital de Clínicas da Universidade Federal do Triângulo Mineiro; 🇧🇷 Uberaba, MG, Brazil

Instituto Orizonti; 🇧🇷 Belo Horizonte, Minas Gerais, Brazil

Eurolatino; 🇧🇷 Juiz De Fora, Minas Gerais, Brazil

Santa Casa da Misericórdia de Passos; 🇧🇷 Passos, Minas Gerais, Brazil

Hospital Universitário Maria Aparecida Pedrossian; 🇧🇷 Campo Grande, MS, Brazil

Pontifícia Universidade Católica do Paraná; 🇧🇷 Curitiba, Paraná, Brazil

Instituto de Medicina Integral Professor Fernando Figueira - IMIP; 🇧🇷 Recife, Pernambuco, Brazil

Hospital Real Português; 🇧🇷 Recife, PE, Brazil

Instituto Atena de Pesquisa; 🇧🇷 Natal, Rio Grande Do Norte, Brazil

Hospital São Lucas; 🇧🇷 Rio De Janeiro, RJ, Brazil

HUPE - Hospital Universitário Pedro Ernesto; 🇧🇷 Rio De Janeiro, RJ, Brazil

Hospital São Lucas da PUCRS; 🇧🇷 Porto Alegre, RS, Brazil

Instituto de Cardiologia do RS - Fundação Universitária de Cardiologi; 🇧🇷 Porto Alegre, RS, Brazil

Hospital Baia Sul; 🇧🇷 Florianópolis, SC, Brazil

Hospital Instituto de Cardiologia de SC; 🇧🇷 Florianópolis, SC, Brazil

Centro de Pesquisa Clínica do Coração; 🇧🇷 Aracaju, SE, Brazil

Hospital Universitário São Francisco na Providência de Deus; 🇧🇷 Bragança Paulista, SP, Brazil

Irmandade da Santa Casa de Misericórdia de Marilia; 🇧🇷 Marilia, SP, Brazil

Instituição, Hospital e Maternidade Celso Pierro; 🇧🇷 Campinas, SP, Brazil

Santa Casa da Misericórdia de Santos; 🇧🇷 Santos, SP, Brazil

Hospital Dante Pazzanese; 🇧🇷 São Paulo, SP, Brazil

Instituto de Assistência Médica ao Servidor Público Estadual; 🇧🇷 São Paulo, SP, Brazil

UPECLIN; 🇧🇷 Botucatu, São Paulo, Brazil

Hospital 9 de Julho; 🇧🇷 São Paulo, SP, Brazil

Instituto do Coração - InCor; 🇧🇷 São Paulo, SP, Brazil

Real e Benemérita Associação Portuguesa de Beneficência; 🇧🇷 São Paulo, SP, Brazil

Santa Casa de São Paulo; 🇧🇷 São Paulo, SP, Brazil

Instituto De Pesquisa Clinica de Campinas; 🇧🇷 Campinas, São Paulo, Brazil

Hospital Regional de Presidente Prudente; 🇧🇷 Presidente Prudente, São Paulo, Brazil

Hospital de Base; 🇧🇷 São José Do Rio Preto, São Paulo, Brazil

Instituto Estadual de Cardiologia Aloysio de Castro; 🇧🇷 Rio De Janeiro, Brazil

Hospital Israelita Albert Einstein; 🇧🇷 São Paulo, Brazil

Hospital São Paulo - Unifesp; 🇧🇷 São Paulo, Brazil