Clinical trial NCT04360720: Percutaneous Coronary Intervention Followed by Antiplatelet Monotherapy in the Setting of Acute Coronary Syndromes
Official title: PercutaNEOus Coronary Intervention Followed by Monotherapy INstead of Dual Antiplatelet Therapy in the SETting of Acute Coronary Syndromes: The NEO-MINDSET Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Acute Coronary Syndrome
Keywords: Acute Coronary Syndrome
Antithrombotic Therapy
Dual Antiplatelet Therapy with acetylsalicylic acid
Monotherapy without acetylsalicylic acid
Lead sponsor: Hospital Israelita Albert Einstein
Sponsor class: OTHER
First posted: 2020-04-24
Enrollment: 3400
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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Composite endpoint of all-cause mortality, cerebrovascular accident, myocardial infarction or urgent target vessel revascularization.
timeFrame: 12 months
measure: Bleeding Academic Research Consortium (BARC) type-2, -3 or -5 bleeding event
timeFrame: 12 months
Secondary outcomes:
measure: Total of deaths, and cardiac and non-cardiac deaths
timeFrame: 12 months
measure: Sudden death
timeFrame: 30 days
measure: Cerebrovascular accident
timeFrame: 12 months
measure: Myocardial Infarction
timeFrame: 12 months
measure: Stent thrombosis
timeFrame: 12 months
measure: Non-scheduled invasive coronary treatment
timeFrame: 12 months
measure: BARC 1-5 type bleeding
timeFrame: 12 months
measure: Composite net adverse event (occurrence of co-primary efficacy endpoint or co-primary safety endpoint)
timeFrame: 12 months
measure: Cost-effectiveness ratio
timeFrame: 12 months
Other outcomes:
Locations:
city: Rio Branco
country: Brazil
facility: Acurácia Serviços Médicos
state: Acre
city: Salvador
country: Brazil
facility: Hospital Ana Nery
state: BA
city: Fortaleza
country: Brazil
facility: Hospital de Messejana Dr. Carlos Alberto Studart Gomes
state: CE
city: Brasília
country: Brazil
facility: Hospital de Base de Brasília
state: DF
city: Brasília
country: Brazil
facility: Instituto Aramari APO
state: DF
city: Linhares
country: Brazil
facility: Instituto Cardiovascular de Linhares
state: ES
city: Vila Velha
country: Brazil
facility: Hospital Evangélico de Vila Velha
state: ES
city: Vitória
country: Brazil
facility: Hospital Santa Casa de Misericórdia de Vitória
state: ES
city: Goiânia
country: Brazil
facility: Universidade Federal de Goiás
state: GO
city: Campo Grande
country: Brazil
facility: CASSEMS
state: Mato Grosso Do Sul
city: Belo Horizonte
country: Brazil
facility: Hospital Felício Rocho
state: MG
city: Belo Horizonte
country: Brazil
facility: Hospital Madre Teresa
state: MG
city: Belo Horizonte
country: Brazil
facility: Hospital Universitário Ciências Médicas de Belo Horizonte
state: MG
city: Poços De Caldas
country: Brazil
facility: Hospital Santa Lucia
state: MG
city: Uberaba
country: Brazil
facility: Hospital de Clínicas da Universidade Federal do Triângulo Mineiro
state: MG
city: Belo Horizonte
country: Brazil
facility: Instituto Orizonti
state: Minas Gerais
city: Juiz De Fora
country: Brazil
facility: Eurolatino
state: Minas Gerais
city: Passos
country: Brazil
facility: Santa Casa da Misericórdia de Passos
state: Minas Gerais
city: Campo Grande
country: Brazil
facility: Hospital Universitário Maria Aparecida Pedrossian
state: MS
city: Curitiba
country: Brazil
facility: Pontifícia Universidade Católica do Paraná
state: Paraná
city: Recife
country: Brazil
facility: Instituto de Medicina Integral Professor Fernando Figueira - IMIP
state: Pernambuco
city: Recife
country: Brazil
facility: Hospital Real Português
state: PE
city: Natal
country: Brazil
facility: Instituto Atena de Pesquisa
state: Rio Grande Do Norte
city: Rio De Janeiro
country: Brazil
facility: Hospital São Lucas
state: RJ
city: Rio De Janeiro
country: Brazil
facility: HUPE - Hospital Universitário Pedro Ernesto
state: RJ
city: Rio De Janeiro
country: Brazil
facility: Instituto Nacional de Cardiologia - INC
state: RJ
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
state: RS
city: Porto Alegre
country: Brazil
facility: Hospital São Lucas da PUCRS
state: RS
city: Porto Alegre
country: Brazil
facility: Instituto de Cardiologia do RS - Fundação Universitária de Cardiologi
state: RS
city: Florianópolis
country: Brazil
facility: Hospital Baia Sul
state: SC
city: Florianópolis
country: Brazil
facility: Hospital Instituto de Cardiologia de SC
state: SC
city: Aracaju
country: Brazil
facility: Centro de Pesquisa Clínica do Coração
state: SE
city: Bragança Paulista
country: Brazil
facility: Hospital Universitário São Francisco na Providência de Deus
state: SP
city: Campinas
country: Brazil
facility: Instituição, Hospital e Maternidade Celso Pierro
state: SP
city: Marilia
country: Brazil
facility: Irmandade da Santa Casa de Misericórdia de Marilia
state: SP
city: Santos
country: Brazil
facility: Santa Casa da Misericórdia de Santos
state: SP
city: São Paulo
country: Brazil
facility: Hospital 9 de Julho
state: SP
city: São Paulo
country: Brazil
facility: Hospital Dante Pazzanese
state: SP
city: São Paulo
country: Brazil
facility: Instituto de Assistência Médica ao Servidor Público Estadual
state: SP
city: São Paulo
country: Brazil
facility: Instituto do Coração - InCor
state: SP
city: São Paulo
country: Brazil
facility: Real e Benemérita Associação Portuguesa de Beneficência
state: SP
city: São Paulo
country: Brazil
facility: Santa Casa de São Paulo
state: SP
city: Botucatu
country: Brazil
facility: UPECLIN
state: São Paulo
city: Campinas
country: Brazil
facility: Instituto De Pesquisa Clinica de Campinas
state: São Paulo
city: Presidente Prudente
country: Brazil
facility: Hospital Regional de Presidente Prudente
state: São Paulo
city: São José Do Rio Preto
country: Brazil
facility: Hospital de Base
state: São Paulo
city: Rio De Janeiro
country: Brazil
facility: Instituto Estadual de Cardiologia Aloysio de Castro
city: São Paulo
country: Brazil
facility: Hospital Israelita Albert Einstein
city: São Paulo
country: Brazil
facility: Hospital São Paulo - Unifesp
Study officials:
affiliation: Hospital Israelita Albert Einstein
name: Pedro A Lemos, MD
role: PRINCIPAL_INVESTIGATOR
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