Rationale, Design, and Clinical Characteristics of the Virginia Anakinra Response Trial 4 (VA-ART4): A Randomized, Placebo-Controlled, Double-Blinded, Two-Center Study

ABSTRACTIntroduction Systemic inflammation during ST-segment elevation myocardial infarction (STEMI), mediated by Interleukin-1 (IL-1), is associated with impaired systolic function and heart failure (HF). Despite advances in reperfusion and neurohormonal therapy, HF incidence post-STEMI remains high, suggesting HF can develop independent of systolic function. Pilot studies show that IL-1 blockade with anakinra suppresses inflammation and reduces HF incidence. Objective To evaluate the effects of IL-1 blockade with anakinra on cardiac reserve and fitness after reperfused STEMI. Methods The Virginia Anakinra Remodeling Trial-4 (VA-ART4; NCT05177822) is a phase II, two-center, double-blind, randomized trial of anakinra 100 mg daily or placebo for up to 14 days in 84 patients with STEMI. Patients with prior MI or HF with reduced ejection fraction, active infection, inflammatory disease, immunosuppression, malignancy, or inability to perform cardiopulmonary exercise testing were excluded. Primary endpoint: peak oxygen consumption (VO₂)(% predicted by Wasserman-Hansen) at 42±7 days. Secondary endpoints: cardiac reserve on stress echocardiography, infarct size and remodeling at cardiac magnetic resonance, quality of life, biomarkers, and HF-related outcomes over 12 months. Expected results IL-1 blockade with anakinra may preserve cardiac reserve and cardiorespiratory fitness after STEMI, and improve quality of life and HF outcomes, informing future phase III studies.