Impact of human serum albumin in acute large-core ischemic stroke: an exploratory randomized controlled trial

Background Anterior-circulation large-vessel occlusion with a large ischemic core remains associated with substantial disability despite successful endovascular therapy (EVT). Human serum albumin (HSA) has shown neuroprotective effects in preclinical models, but its clinical benefit after successful reperfusion is uncertain. Methods We conducted a single-center, prospective, open-label, endpoint-blinded exploratory randomized controlled trial in 60 adults with anterior-circulation large-core acute ischemic stroke due to large-vessel occlusion. Participants were randomized 1:1 before EVT. After angiographic confirmation of successful reperfusion (eTICI 2b-3), the albumin group received 100 mL of 20% HSA intravenously and the control group received 100 mL of normal saline with matched timing. The primary outcome was 90-day functional independence (modified Rankin Scale score 0–2). Net water uptake (NWU) was an exploratory imaging biomarker; symptomatic intracranial hemorrhage (sICH) and 90-day mortality were safety outcomes. Results All 60 randomized participants achieved successful reperfusion, received the allocated intervention, and were included in the intention-to-treat analysis. In the albumin and control groups, respectively, 21/30 (70.0%) and 20/30 (66.7%) participants were male; mean ± SD age was 68.0 ± 9.3 and 66.3 ± 10.7 years, admission National Institutes of Health Stroke Scale (NIHSS) score was 16.3 ± 4.8 and 16.4 ± 7.1, and admission Alberta Stroke Program Early CT Score (ASPECTS) on noncontrast CT (NCCT) was 5.0 ± 1.5 and 4.9 ± 1.3. Functional independence occurred in 11/30 participants (36.7%) in each group (risk ratio, 1.00 [95% CI, 0.51–1.94]; risk difference, 0.0 percentage points [95% CI, −24.4 to 24.4]; odds ratio, 1.00 [95% CI, 0.35–2.86]; Fisher exact p = 1.000). The NWU treatment-by-time interaction was not statistically significant (Wald chi-square = 3.40, 2 df; p = 0.182). sICH occurred in 2/30 participants (6.7%) in each group, and 90-day mortality occurred in 2/30 (6.7%) versus 4/30 (13.3%). Conclusion In this small exploratory randomized trial, immediate post-reperfusion 20% HSA did not demonstrate a statistically significant improvement in 90-day functional independence or NWU. Wide confidence intervals do not exclude clinically meaningful benefit or harm; larger adequately powered multicenter trials are needed. Clinical trial registration https://clinicaltrials.gov/study/NCT06629116 ; Unique Identifier: NCT06629116.