Acute Coronary Syndrome
Conditions
Keywords
Acute Coronary Syndrome, Antithrombotic Therapy, Dual Antiplatelet Therapy with acetylsalicylic acid, Monotherapy without acetylsalicylic acid
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.
Interventions
DRUGAntiplatelet 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 until the end of the study, at Month 12.
Sponsors
Hospital Israelita Albert Einstein
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects must meet all the criteria below: 1. Age \>=18 years; 2. Acute coronary syndrome with last symptoms \< 24 hours before hospital 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 conservatively or with unsuccessful percutaneous intervention or coronary artery bypass graft; 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 stroke \< 30 days; 9. Presence of brain arteriovenous malformation; 10. Index event of non-atherothrombotic etiology (i.e., stent thrombosis, in-stent restenosis, 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 to 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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite endpoint of all-cause mortality, stroke, 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
| Measure | Time frame | Description |
|---|---|---|
| Stroke | 12 months | Stroke |
| Myocardial Infarction | 12 months | Myocardial Infarction |
| Stent thrombosis | 12 months | Stent thrombosis |
| All-cause death, cardiovascular death and non-cardiovascular death | 12 months | All-cause death, cardiovascular death and non-cardiovascular death |
| BARC 1-5 type bleeding | 12 months | BARC 1-5 type bleeding |
| Net adverse clinical events (occurrence of all-cause death, myocardial infarction, stroke, urgent target-vessel revascularization, BARC 2, 3 or 5 bleeding) | 12 months | Net adverse clinical events (occurrence of all-cause death, myocardial infarction, stroke, urgent target-vessel revascularization, BARC 2, 3 or 5 bleeding) |
| Cost-effectiveness ratio | 12 months | Cost-effectiveness ratio |
| Unscheduled invasive coronary treatment | 12 months | Unscheduled invasive coronary treatment |
| Sudden death | 30 days | Sudden death |
Countries
Brazil
Outcome results
None listed