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
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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
WHAT IS ALREADY KNOWN ON THIS TOPIC
Patients with acute ischemic stroke (AIS) attributable to symptomatic intracranial atherosclerotic disease (sICAD) remain at high risk of early neurological deterioration (END) despite standard medical treatment. Previous studies suggested that PCSK9 inhibitors, when added to statin therapy, could rapidly lower LDL-C levels and might reduce END in patients with AIS, but randomized evidence in AIS attributable to sICAD remains limited.
WHAT THIS STUDY ADDS
The CAPTAIN trial evaluates the efficacy and safety of the early addition of a PCSK9 inhibitor to statin therapy in patients with AIS attributable to sICAD. This protocol describes the rationale, design, outcomes, and statistical analysis plan of the trial.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
CAPTAIN is expected to provide randomized evidence on whether the early addition of a PCSK9 inhibitor to statin therapy reduces END in patients with AIS attributable to sICAD. The findings may inform future research and acute phase lipid-lowering strategies for this high-risk stroke population.
