Pre-hospital treatment with zalunfiban (RUC-4) in patients with ST- Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: Rationale and design of the CELEBRATE trial.

BACKGROUND: Early and complete restoration of target vessel patency in ST-elevation myocardial infarction (STEMI) is associated with improved outcomes. Oral P2Y12 inhibitors have failed to demonstrate either improved patency or reduced mortality when administered in the pre-hospital setting. Thus, there is a need for antiplatelet agents that achieve prompt and potent platelet inhibition, and that restore patency in the pre-hospital setting. Zalunfiban, a novel subcutaneously administered glycoprotein IIb/IIIa inhibitor designed for pre-hospital administration, has shown to achieve rapid, high-grade platelet inhibition that exceeds that of P2Y12 inhibitors. Whether pre-hospital administration of zalunfiban can improve clinical outcome is unknown.

HYPOTHESIS: The present study is designed to assess the hypothesis that a single, pre-hospital injection of zalunfiban given in the ambulance, in addition to standard-of-care in patients with STEMI with intent to undergo primary percutaneous coronary intervention (PCI) will improve clinical outcome compared to standard-of-care with placebo.

STUDY DESIGN: The ongoing CELEBRATE trial (NCT04825743) is a phase III, randomized, double-blinded, placebo-controlled, international trial. Patients with STEMI intended to undergo primary PCI will receive treatment with a single subcutaneous injection containing either zalunfiban dose 1 (0.110 mg/kg), zalunfiban dose 2 (0.130 mg/kg) or placebo, and the study drug will be administered in the ambulance before transportation to the hospital. A target of 2499 patients will be randomly assigned to one of the treatment groups in a 1:1:1 ratio, i.e., to have approximately 833 evaluable patients per group. The primary efficacy outcome is a ranked 7-point scale on clinical outcomes. The primary safety outcome is severe or life-threatening bleeding according to the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) criteria.

SUMMARY: The CELEBRATE trial will assess whether a single pre-hospital subcutaneous injection of zalunfiban in addition to standard-of-care in patients with STEMI with intent to undergo primary PCI will result in improved clinical outcome.