Pre-Hospital Pulse Glucocorticoid Therapy in Patients with ST-Segment Elevation Myocardial Infarction Transferred for Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (PULSE-MI)

Abstract

Abstract Background Inflammation in ST-segment elevation myocardial infarction (STEMI) is an important contributor to both acute myocardial ischemia and reperfusion injury after primary percutaneous coronary intervention (PCI). Methylprednisolone is a glucocorticoid with potent anti-inflammatory properties with an acute effect and is used as an effective and safe treatment of a wide range of acute diseases. The trial aims to investigate the cardioprotective effects of pulse-dose methylprednisolone administered in the pre-hospital setting in patients with STEMI transferred for primary PCI. Methods This trial is a randomized, blinded, placebo-controlled prospective clinical phase II trial. Inclusion will continue until 378 patients with STEMI have been evaluated for the primary endpoint. Patients will be randomized 1:1 to a bolus of 250 mg methylprednisolone intravenous or matching placebo over a period of 5 minutes in the pre-hospital setting. All patients with STEMI transferred for primary PCI at Rigshospitalet, Copenhagen University Hospital, Denmark will be screened for eligibility. The main eligibility criteria are age ≥ 18 years, acute onset of chest pain with < 12 hours duration, STEMI on electrocardiogram, no known allergy to glucocorticoids or no previous coronary artery bypass grafting, previous acute myocardial infarction in assumed culprit, or a history with previous maniac/psychotic episodes. Primary outcome is final infarct size measured by late gadolinium enhancement on cardiac magnetic resonance (CMR) three months after STEMI. Secondary outcomes compromise key CMR efficacy parameters, clinical endpoints at three months, the peak of cardiac biomarkers, and safety. Discussion We hypothesize that pulse-dose methylprednisolone administrated in the pre-hospital setting decreases inflammation, and thus reduces final infarct size in patients with STEMI treated with primary PCI. Trial registration EU-CT number: 2022-500762-10-00; Submitted May 5, 2022. ClinicalTrials.gov Identifier: NCT05462730; Submitted July 7, 2022, first posted July 18, 2022