Combined Antioxidant Therapy for Acute Myocardial Infarction

Acute myocardial infarction (AMI) remains as a leading cause of morbidity and mortalityworldwide. In patients with ST‐segment elevation myocardial infarction (STEMI), earlyreperfusion with primary percutaneous coronary intervention (PCI) is the standardtreatment to limit myocardial injury. However, reperfusion induces additional damage,referred to as ischemia‐reperfusion injury (IRI), which has been estimated to account forup to 50% of final infarct size. Oxidative stress is a key mechanism in IRI andcontributes to lipid peroxidation, inflammation, and regulated cell death pathways. Priorpharmacologic approaches directed at single components of this process have shown limitedand inconsistent clinical benefit, supporting evaluation of multitarget strategies.This study is a phase II, randomized, double‐blind, placebo‐controlled, parallel‐groupsuperiority trial designed to evaluate the efficacy and safety of a combined antioxidanttherapy (CAT) in patients with acute STEMI undergoing primary PCI. CAT consists ofascorbate, N‐acetylcysteine, and deferoxamine. These agents were selected to targetcomplementary mechanisms relevant to IRI: reactive oxygen species scavenging, glutathionereplenishment, redox modulation and inflammatory response, and iron chelation withinhibition of iron‐dependent lipid peroxidation. The study will randomly assignparticipants in a 1:1 ratio to receive CAT or matching placebo in addition toguideline‐based STEMI treatment.The intervention will be initiated before reperfusion and maintained during primary PCIin order to ensure drug exposure during the early reperfusion phase. Both groups willreceive standard‐of‐care treatment for STEMI, including primary PCI andguideline‐directed medical therapy.The trial is designed as a signal‐seeking phase II study using infarct size as theprimary efficacy endpoint. Infarct size measured by cardiac magnetic resonance (CMR) is amechanistically relevant endpoint in cardioprotection trials and has establishedprognostic value. In this study, CMR will be performed during the index hospitalizationto quantify infarct size as a percentage of left ventricular mass. Additional imagingvariables, myocardial injury biomarkers, oxidative stress and inflammatory biomarkers,pharmacokinetic measurements, short‐term clinical outcomes, and safety data will becollected to support interpretation of the primary analysis. These assessments includeleft ventricular systolic function, hs‐cTnI, CK, CK‐MB, plasma concentrations of thestudy drugs, and 30‐day follow‐up for clinical events and adverse events.The planned sample size is 46 participants. The study is powered to detect a largebetween‐group difference in infarct size, consistent with its exploratory phase IIdesign. Accordingly, the trial is intended to determine whether CAT demonstrates asufficiently large efficacy signal, together with an acceptable safety profile, tosupport further evaluation in a larger trial.Safety monitoring will include systematic collection of adverse events and seriousadverse events during hospitalization and through day 30. Events will be recorded usingMedical Dictionary for Regulatory Activities (MedDRA) terminology.This trial will provide phase II data on the efficacy, safety, pharmacokinetics, andmechanistic effects of a multitarget antioxidant strategy administered during primary PCIin patients with STEMI.