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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Acute Coronary Syndrome

Intervention / Treatment
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* Drug: Antiplatelet Monotherapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Dual Antiplatelet Therapy<br>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<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Coronary Syndrome, Antithrombotic Therapy, Dual Antiplatelet Therapy with acetylsalicylic acid, Monotherapy without acetylsalicylic acid