Role of Immune Responses After Acute Myocardial Infarction (BATTLE-AMI)

Federal University of São Paulo

Status and phase: Unknown; Phase 4

Conditions: Myocardial Fibrosis

Treatments: Drug: Rosuvastatin plus ticagrelor; Drug: Rosuvastatin plus clopidogrel; Drug: Simvastatin plus ticagrelor; Drug: Simvastatin plus clopidogrel

Study type: Interventional

Funder types: Other

Identifiers

NCT02428374

FAPESP (Other Identifier)

EPM/UNIFESP

Details and patient eligibility

About

The fascinating role of lymphocyte subtypes in the development of coronary artery disease may be a new strategic target for understanding and therapy of acute myocardial infarction. The determinants of cell viability are unknown, postulating that they arise from factors not only related to microcirculation or energy expenditure, but also to inflammatory and immune responses. Furthermore, the intense mobilization of progenitor cells secondary to myocardial infarction triggers large lymphocyte proliferation that colonizes plaques in development, contributing to recurrent ischemic outcomes. This project aims to evaluate the immune and metabolic mechanisms involved in the recovery of the ischemic myocardium and coronary disease progression.

Full description

Specifically, the investigators will study the innate and adaptive immunity, with emphasis on lymphocytes subtypes involved in the early and late surrogate outcomes of patients with acute myocardial infarction, their characterization (B1, B2 and T lymphocytes) in cell culture and by flow-cytometry, and immune responses (IgM and IgG for oxLDL and specific epitopes of apoB). In addition, the project will evaluate new biomarkers identified by studies of metabolomics, as well as the corresponding signaling pathways. Therapeutic pharmacological strategies and changes on intestinal microbiota will be evaluated since the acute phase of myocardial infarction up to 6 months.

In the study, the investigators will compared four arms of combined therapy: clopidogrel with rosuvastatin; or clopidogrel with simvastatin; or ticagrelor with rosuvastatin; or ticagrelor with simvastatin. The investigator's hypothesis is that the improvement of microcirculation with rosuvastatin and ticagrelor (synergic pleiotropic effects) may decrease the infarcted mass area, resulting in better left ventricular ejection fraction when compared to the other combined therapies.

The monitoring and genotype of microbiota will be examined together the metabolomics and cardiac MRIs obtained at the acute phase of MI and after 1-mo and 6-mo FU.

Enrollment: 300 estimated patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Stable patients with ST elevation myocardial infarction (STEMI) treated with thrombolytics in the first 6h or the initial of symptoms of MI.

Exclusion criteria

1. Contraindication or known intolerance to the study drug protocol
2. Those with comorbidities such as neoplasm, renal insufficiency (stage 4 or higher)

Patients should be randomized in the first 24 hours of AMI and treated by one of the four combined therapies at least 2h prior to coronary angiogram followed by percutaneous intervention when necessary.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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300 participants in 4 patient groups

rosuvastatin plus clopidogrel

Active Comparator group

Description:

rosuvastatin 40 mg and clopidogrel 75 mg

Treatment:

Drug: Simvastatin plus ticagrelor

Drug: Simvastatin plus clopidogrel

Drug: Rosuvastatin plus ticagrelor

Rosuvastatin plus ticagrelor

Active Comparator group

Description:

Rosuvastatin 40 mg plus ticagrelor 90 mg bid

Treatment:

Drug: Simvastatin plus ticagrelor

Drug: Simvastatin plus clopidogrel

Drug: Rosuvastatin plus clopidogrel

simvastatin plus clopidogrel

Active Comparator group

Description:

Simvastatin 40 mg plus clopidogrel 75 mg

Treatment:

Drug: Simvastatin plus ticagrelor

Drug: Rosuvastatin plus clopidogrel

Drug: Rosuvastatin plus ticagrelor

Simvastatin plus ticagrelor

Active Comparator group

Description:

Simvastatin 40 mg plus ticagrelor 90 mg bid

Treatment:

Drug: Simvastatin plus clopidogrel

Drug: Rosuvastatin plus clopidogrel

Drug: Rosuvastatin plus ticagrelor