Albumin for patients with acute large vessel occlusive stroke undergoing endovascular therapy-2 (ARISE-2): protocol for a randomised controlled trial

Abstract Background Endovascular therapy is the standard of care for eligible patients with acute ischemic stroke due to LVO. However, nearly half of patients remain functionally dependent even after successful reperfusion. Albumin is a biologically plausible adjunctive cerebroprotective therapy and has shown neuroprotective effects in preclinical studies, but the clinical benefit of albumin combined with EVT remains uncertain. Study design Albumin for patients with acute large vessel occlusive stroke undergoing endovascular therapy-2 (ARISE-2) is an investigator-initiated, prospective, multicenter, randomised, open-label, controlled trial with blinded endpoint assessment (PROBE design). Eligible participants will be randomly assigned in a 1:1 ratio to receive either EVT plus intravenous 25% albumin at 0.5 g/kg (maximum dose, 37.5 g) initiated within 60 min after randomisation and then repeated once daily on days 2–4, or EVT alone. The initial target sample size is 1192 participants (596 per group). A prespecified adaptive sample size re-estimation will be performed after approximately 50% of participants have completed the 90-day follow-up, allowing the total sample size to be increased, but not reduced, to a maximum of 1788 participants. This trial aims to evaluate the efficacy and safety of albumin administered in combination with EVT in patients with acute ischemic stroke caused by anterior circulation LVO. Study endpoints The primary outcome is a favourable functional outcome at 90 days, defined as a mRS score of 0–2, or return to the premorbid mRS for participants with a prestroke mRS score of 3–4. Summary The ARISE-2 trial is designed to evaluate the efficacy and safety of moderate-dose albumin combined with EVT in participants with acute ischemic stroke caused by anterior circulation LVO. The trial will provide evidence on whether albumin can improve functional outcomes as an adjunctive cerebroprotective strategy in patients undergoing reperfusion therapy. Trial registration ClinicalTrials.gov: NCT07263308.