Role of Innate and Adaptive Immunity After Acute Myocardial Infarction BATTLE-AMI Study (B And T Types of Lymphocytes Evaluation in Acute Myocardial Infarction)
Trial Snapshot
- Phase
- Phase 4
- Sponsor
- Enrollment
- 300
- Locations
- 1
- Primary Endpoint
- Comparison of the left ventricular function (MRI) between the four combined treatments, after STEMI
Study Overview
Brief Summary
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.
Detailed 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 85 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Stable patients with ST elevation myocardial infarction (STEMI) treated with thrombolytics in the first 6h or the initial of symptoms of MI.
Exclusion Criteria
- •Contraindication or known intolerance to the study drug protocol
- •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.
Arms & Interventions
rosuvastatin plus clopidogrel
rosuvastatin 40 mg and clopidogrel 75 mg
Intervention: Rosuvastatin plus ticagrelor (Drug)
rosuvastatin plus clopidogrel
rosuvastatin 40 mg and clopidogrel 75 mg
Intervention: Simvastatin plus clopidogrel (Drug)
rosuvastatin plus clopidogrel
rosuvastatin 40 mg and clopidogrel 75 mg
Intervention: Simvastatin plus ticagrelor (Drug)
Rosuvastatin plus ticagrelor
Rosuvastatin 40 mg plus ticagrelor 90 mg bid
Intervention: Rosuvastatin plus clopidogrel (Drug)
Rosuvastatin plus ticagrelor
Rosuvastatin 40 mg plus ticagrelor 90 mg bid
Intervention: Simvastatin plus clopidogrel (Drug)
Rosuvastatin plus ticagrelor
Rosuvastatin 40 mg plus ticagrelor 90 mg bid
Intervention: Simvastatin plus ticagrelor (Drug)
simvastatin plus clopidogrel
Simvastatin 40 mg plus clopidogrel 75 mg
Intervention: Rosuvastatin plus clopidogrel (Drug)
simvastatin plus clopidogrel
Simvastatin 40 mg plus clopidogrel 75 mg
Intervention: Rosuvastatin plus ticagrelor (Drug)
simvastatin plus clopidogrel
Simvastatin 40 mg plus clopidogrel 75 mg
Intervention: Simvastatin plus ticagrelor (Drug)
Simvastatin plus ticagrelor
Simvastatin 40 mg plus ticagrelor 90 mg bid
Intervention: Rosuvastatin plus clopidogrel (Drug)
Simvastatin plus ticagrelor
Simvastatin 40 mg plus ticagrelor 90 mg bid
Intervention: Rosuvastatin plus ticagrelor (Drug)
Simvastatin plus ticagrelor
Simvastatin 40 mg plus ticagrelor 90 mg bid
Intervention: Simvastatin plus clopidogrel (Drug)
Outcomes
Primary Outcomes
Comparison of the left ventricular function (MRI) between the four combined treatments, after STEMI
Time Frame: 1-mo
The effects of treatments on the left ventricular function will be measured by MRI
Secondary Outcomes
- To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with infarcted mass area after STEMI(6-mo)
- To compare the effects of the four combined therapies on the infarcted mass area after STEMI(6-mo)
- To compare the effects of the four combined therapies on the left ventricular function after STEMI(6-mo)
- To compare the effects of the four combined therapies on the percentage of subjects with left ventricular ejection fraction < 40% after STEMI(6-mo)
- To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with left ventricular ejection fraction <40% after STEMI(6-mo)
- To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with left ventricular ejection fraction after STEMI(6-mo)
Investigators
Francisco Antonio Helfenstein Fonseca
Affiliate Professor of Medicine
Federal University of São Paulo