ABSTRACT NUMBER: ESOC2026A2388 CEREBRAL BIOAVAILABILITY, SAFETY AND FEASIBILITY OF INTRAVENOUS LACTATE ADMINISTRATION AFTER ACUTE ISCHEMIC STROKE: RESULTS FROM THE RANDOMIZED CONTROLLED PHASE IIA “LACAVC” TRIAL

Abstract Background and aims Lactate is an alternative energy substrate with neuroprotective effects in experimental acute ischemic stroke (AIS). We aimed to assess feasibility and safety of intravenous lactate administered after endovascular treatment (EVT) for AIS, and assess whether exogenous lactate reaches healthy and ischemic brain tissue in humans. Methods In this randomized, double-blind, placebo-controlled phase IIa trial (LacAVC-NCT04858139), adults with AIS with proximal anterior-circulation large-vessel occlusion undergoing EVT (+/-IVT), were randomized 1:1 to receive intravenous sodium lactate (300 mmol/L over 20 minutes) or placebo after recanalization. MRI including proton magnetic resonance spectroscopy (MRS) was performed at baseline, immediately after infusion, and at 24 hours. Primary outcome was cerebral bioavailability of exogenous lactate, assessed by changes in the lactate-to-creatine (Lac/Cr) ratio between baseline and post-infusion MRI within ischemic core, hypoperfused tissue, and contralateral brain. Results Eleven patients received IV sodium lactate and 10 placebo. Median age was 73 years, 52% were female, median baseline NIHSS was 12, 57% received IVT, and median onset-to-groin and EVT-to-infusion times were 303 and 32 minutes, respectively. No infusion-related complications occurred. Ten serious adverse events were reported in 9 patients (6 with lactate, 4 with placebo), none related to the investigational product. Lactate infusion significantly increased the Lac/Cr ratio in healthy brain tissue (P < 0.001) but not the ischemic core or penumbra. Conclusions This first-in-human phase IIa trial shows that intravenous lactate after reperfusion in AIS is feasible, appears safe, and reaches the human brain, providing biological proof-of-concept and support larger trials evaluating lactate-based neuroprotection. Conflict of interest All authors: Nothing to disclose. Figure 1 - belongs to Results