Zalunfiban at First Medical Contact for STEMI — CELEBRATE Trial
Zalunfiban at First Medical Contact for STEMI — CELEBRATE Trial
Source: NEJM Evidence, Nov 10 2025
Keynotes:
1- Background
• Zalunfiban (RUC-4) is a new subcutaneous GPIIb/IIIa inhibitor designed for rapid platelet blockade at first medical contact (FMC) in ST-elevation myocardial infarction (STEMI).
• Aim: To determine if early parenteral platelet inhibition improves infarct-artery patency and short-term outcomes without excess bleeding.
2-Study Design
• Phase 3, international, randomized, double-blind, placebo-controlled trial.
• 2,467 STEMI patients enrolled across 8 countries (2021 – 2025).
• Randomized 1:1:1 to:
• Zalunfiban 0.11 mg/kg (n = 853)
• Zalunfiban 0.13 mg/kg (n = 818)
• Placebo (n = 796)
• Drug administered at FMC — home, ambulance, or ED.
• Most patients also received aspirin + heparin ± ticagrelor.
• Primary efficacy endpoint: 30-day hierarchical composite (death, stroke, recurrent MI, stent thrombosis, HF, large MI, or no event).
• Primary safety endpoint: Severe/life-threatening bleeding (GUSTO criteria).
3- Main Results
• Efficacy:
• Adjusted OR = 0.79 (95 % CI) vs placebo → significant clinical benefit. OR (Odds Ratio – a statistical measure indicating the strength of association between a risk factor and an outcome; values >1 suggest higher odds(higher probability)and <1 suggest lower odds).
• “No event” rate: 13.3 % vs 9.8 %, absolute risk reduction 3.5 %; ≈ 29 patients needed to treat.
• Faster TIMI flow
• Lower stent-thrombosis (0.2 % vs 1.0 %) and fewer large MIs or new-onset HF.
• Safety:
• Severe/life-threatening bleeding: 1.2 % vs 0.8 % (p = 0.40) → no significant difference(p < 0.001 – indicates a highly statistically significant result, meaning the finding is very unlikely due to chance — less than 0.1% probability, while a result with p > 0.05 is generally considered not statistically significant)
• Mild–moderate bleeding: 6.4 % vs 2.5 % (p < 0.001).
• Thrombocytopenia (<150k/μL): 8.1 % vs 6.3 %, mostly grade 1.
• Intracranial hemorrhage: 0.4 % vs 0.6 %.
4- Interpretation
• A single subcutaneous dose at FMC improved early infarct-artery patency and 30-day composite outcomes, without higher major-bleeding risk.
• Represents a potential paradigm shift: converting GPIIb/IIIa infusion into a field-ready injection usable before PCI.
• Mild bleeding increase warrants monitoring.
5- Expert Commentary
•. Arnoud van ’t Hof – Maastricht University (Netherlands) et al.: “These data highlight the efficacy and safety of early subcutaneous platelet inhibition as an adjunct to reperfusion therapy in STEMI.”
• Editorial (d’Entremont & Jolly): CELEBRATE “revives upstream GPIIb/IIIa therapy” by offering an easy-to-use, rapidly reversible option; further outcome trials are needed before changing guidelines.
6- Clinical Implications
• Upstream parenteral platelet inhibition may enhance pre-PCI reperfusion beyond oral P2Y₁₂ agents.
• Current guidelines (AHA 2025 / ESC 2023) still recommend early oral DAPT; zalunfiban is investigational pending larger mortality-focused trials.
