Efficacy and safety of early combined therapy with PCSK9 inhibitor and statin in acute ischemic stroke (CAPTAIN): protocol of a multicenter, prospective, open-label, randomized trial

Background Patients with acute ischemic stroke (AIS) attributable to symptomatic intracranial atherosclerotic disease (sICAD) remain at substantial risk of early neurological deterioration (END) despite standard medical treatment. Aim To determine whether early addition of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to statin therapy reduces END in patients with AIS attributable to sICAD within 48 hours of symptom onset. Design The study of Combined Therapy with PCSK9 Inhibitor and Statin in Acute Ischemic Stroke (CAPTAIN) is a multicenter, prospective, randomized, open-label, blinded-endpoint trial conducted in China, with a planned sample size of 416 patients. Eligible patients will be randomized in a 1:1 ratio to receive either early evolocumab plus standard-dose statin or standard-dose statin therapy. Outcomes The primary efficacy outcome is the occurrence of END within 3 days after randomization, defined as an increase in the National Institutes of Health Stroke Scale score of at least 2 points from baseline. Secondary efficacy outcomes include neurological improvement, changes in National Institutes of Health Stroke Scale (NIHSS) score, shift in the 90-day modified Rankin Scale score distribution, recurrent stroke, and changes in lipid parameters. The primary safety outcome is the incidence of moderate-to-severe systemic bleeding within 3 days after randomization, as defined by the GUSTO criteria. Conclusions This study is expected to provide evidence on the efficacy and safety of the early addition of a PCSK9 inhibitor to statin therapy in patients with AIS attributable to sICAD. Trial registration number NCT06696820