NEOMINDSET: PercutaNEOus Coronary Intervention Followed by Monotherapy INstead of Dual Antiplatelet Therapy in the SETting of Acute Coronary Syndromes: The NEO-MINDSET Trial

Sponsor

Hospital Israelita Albert Einstein (Other)

Overall Status

Recruiting

CT.gov ID

NCT04360720

Collaborator

(none)

3,400

Enrollment

Locations

Arms

39.5

Anticipated Duration (Months)

69.4

Patients Per Site

1.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Coronary Syndrome	Drug: Antiplatelet Monotherapy	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

3400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

PercutaNEOus Coronary Intervention Followed by Monotherapy INstead of Dual Antiplatelet Therapy in the SETting of Acute Coronary Syndromes: The NEO-MINDSET Trial A Drug Reduction Study for Patients With Acute Coronary Syndrome in the Unified Health System in Brazil

Actual Study Start Date :

Oct 15, 2020

Anticipated Primary Completion Date :

Jan 30, 2024

Anticipated Study Completion Date :

Jan 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Dual Antiplatelet Therapy Subjects randomized to Dual Antiplatelet Therapy Control Group will be treated with a regimen of acetylsalicylic acid combined with ticagrelor or prasugrel for 12 months. Acetylsalicylic acid (100 mg/day) + ticagrelor (90 mg twice daily) Or Acetylsalicylic acid (100 mg/day) + prasugrel (10 mg once daily)
Experimental: Antiplatelet Monotherapy All subjects randomized to Monotherapy Group will have acetylsalicylic acid discontinued immediately after randomization. Subjects randomized to 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)	Drug: Antiplatelet Monotherapy All subjects randomized to Monotherapy Group will have acetylsalicylic acid discontinued immediately after randomization. Subjects randomized to Monotherapy Group will be treated with ticagrelor or prasugrel alone until the end of the study, at Month 12.

Arm

Intervention/Treatment

No Intervention: Dual Antiplatelet Therapy

Subjects randomized to Dual Antiplatelet Therapy Control Group will be treated with a regimen of acetylsalicylic acid combined with ticagrelor or prasugrel for 12 months. Acetylsalicylic acid (100 mg/day) + ticagrelor (90 mg twice daily) Or Acetylsalicylic acid (100 mg/day) + prasugrel (10 mg once daily)

Experimental: Antiplatelet Monotherapy

All subjects randomized to Monotherapy Group will have acetylsalicylic acid discontinued immediately after randomization. Subjects randomized to 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)

Drug: Antiplatelet Monotherapy

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Total of deaths, and cardiac and non-cardiac deaths [12 months]
Total of deaths, and cardiac and non-cardiac deaths
Sudden death [30 days]
Sudden death
Cerebrovascular accident [12 months]
Cerebrovascular accident
Myocardial Infarction [12 months]
Myocardial Infarction
Stent thrombosis [12 months]
Stent thrombosis
Non-scheduled invasive coronary treatment [12 months]
Non-scheduled invasive coronary treatment
BARC 1-5 type bleeding [12 months]
BARC 1-5 type bleeding
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects must meet all the criteria below:

Age >=18 years;
Clinical presentation compatible with acute coronary syndrome with onset < 24 hours before admission;
Successful percutaneous coronary intervention(s) of all target lesions (culprit and non-culprit) with new-generation drug-eluting stents;
Length of stay in hospital at randomization < 96 hours;
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:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Acurácia Serviços Médicos	Rio Branco	Acre	Brazil
2	Hospital Ana Nery	Salvador	BA	Brazil
3	Hospital de Messejana Dr. Carlos Alberto Studart Gomes	Fortaleza	CE	Brazil
4	Hospital de Base de Brasília	Brasília	DF	Brazil
5	Instituto Aramari APO	Brasília	DF	Brazil
6	Instituto Cardiovascular de Linhares	Linhares	ES	Brazil
7	Hospital Evangélico de Vila Velha	Vila Velha	ES	Brazil
8	Hospital Santa Casa de Misericórdia de Vitória	Vitória	ES	Brazil
9	Universidade Federal de Goiás	Goiânia	GO	Brazil
10	CASSEMS	Campo Grande	Mato Grosso Do Sul	Brazil
11	Hospital Felício Rocho	Belo Horizonte	MG	Brazil
12	Hospital Madre Teresa	Belo Horizonte	MG	Brazil
13	Hospital Universitário Ciências Médicas de Belo Horizonte	Belo Horizonte	MG	Brazil
14	Hospital Santa Lucia	Poços De Caldas	MG	Brazil
15	Hospital de Clínicas da Universidade Federal do Triângulo Mineiro	Uberaba	MG	Brazil
16	Instituto Orizonti	Belo Horizonte	Minas Gerais	Brazil
17	Eurolatino	Juiz De Fora	Minas Gerais	Brazil
18	Santa Casa da Misericórdia de Passos	Passos	Minas Gerais	Brazil
19	Hospital Universitário Maria Aparecida Pedrossian	Campo Grande	MS	Brazil
20	Pontifícia Universidade Católica do Paraná	Curitiba	Paraná	Brazil
21	Instituto de Medicina Integral Professor Fernando Figueira - IMIP	Recife	Pernambuco	Brazil
22	Hospital Real Português	Recife	PE	Brazil
23	Instituto Atena de Pesquisa	Natal	Rio Grande Do Norte	Brazil
24	Hospital São Lucas	Rio De Janeiro	RJ	Brazil
25	HUPE - Hospital Universitário Pedro Ernesto	Rio De Janeiro	RJ	Brazil
26	Instituto Nacional de Cardiologia - INC	Rio De Janeiro	RJ	Brazil
27	Hospital de Clínicas de Porto Alegre	Porto Alegre	RS	Brazil
28	Hospital São Lucas da PUCRS	Porto Alegre	RS	Brazil
29	Instituto de Cardiologia do RS - Fundação Universitária de Cardiologi	Porto Alegre	RS	Brazil
30	Hospital Baia Sul	Florianópolis	SC	Brazil
31	Hospital Instituto de Cardiologia de SC	Florianópolis	SC	Brazil
32	Centro de Pesquisa Clínica do Coração	Aracaju	SE	Brazil
33	Hospital Universitário São Francisco na Providência de Deus	Bragança Paulista	SP	Brazil
34	Instituição, Hospital e Maternidade Celso Pierro	Campinas	SP	Brazil
35	Irmandade da Santa Casa de Misericórdia de Marilia	Marilia	SP	Brazil
36	Santa Casa da Misericórdia de Santos	Santos	SP	Brazil
37	Hospital 9 de Julho	São Paulo	SP	Brazil
38	Hospital Dante Pazzanese	São Paulo	SP	Brazil
39	Instituto de Assistência Médica ao Servidor Público Estadual	São Paulo	SP	Brazil
40	Instituto do Coração - InCor	São Paulo	SP	Brazil
41	Real e Benemérita Associação Portuguesa de Beneficência	São Paulo	SP	Brazil
42	Santa Casa de São Paulo	São Paulo	SP	Brazil
43	UPECLIN	Botucatu	São Paulo	Brazil
44	Instituto De Pesquisa Clinica de Campinas	Campinas	São Paulo	Brazil
45	Hospital Regional de Presidente Prudente	Presidente Prudente	São Paulo	Brazil
46	Hospital de Base	São José Do Rio Preto	São Paulo	Brazil
47	Instituto Estadual de Cardiologia Aloysio de Castro	Rio De Janeiro		Brazil
48	Hospital Israelita Albert Einstein	São Paulo		Brazil	05652- 900
49	Hospital São Paulo - Unifesp	São Paulo		Brazil