PCSK9 inhibition in patients with acute stroke and symptomatic intracranial atherosclerosis: Protocol for a prospective, randomised, open-label, blinded end-point trial with vessel-wall MR imaging

Introduction Dual antiplatelet therapy and high-intensity statins are the mainstay treatment in patients with acute stage, symptomatic intracranial atherosclerotic stenosis (ICAS). Alirocumab is a monoclonal antibody that can inhibit proprotein convertase subtilisin-kexin type 9 and effectively lower low-density lipoprotein cholesterol levels with less side effects than statins. We hypothesise that alirocumab treatment in addition to statin therapy could stabilise intracranial plaque and reduce arterial stenosis. Methods and analysis In this prospective, randomised, open-label, blinded end-point study, we will use high-resolution vessel-wall MRI to evaluate the efficacy and safety of alirocumab in patients who had an acute ischaemic stroke from ICAS. We will recruit 66 patients who had an acute ischaemic stroke within 7 days of symptom onset, who had symptomatic intracranial artery stenosis (>30%) at the middle cerebral artery, basilar artery or intracranial internal carotid artery. Among them, 22 patients will be randomised to the intervention group to receive treatment with 75 mg alirocumab subcutaneously every 2 weeks for a total of 26 weeks, while those in the control group will not. All patients in both groups will receive antiplatelet agents and high-intensity statins, including 20 mg rosuvastatin or 40-80 mg atorvastatin or at the maximum tolerated dose. All of them will undergo MRI at recruitment and after 26 weeks. The primary outcomes are changes in intracranial atherosclerotic plaques in the MRI before and after 6 months treatment. This trial is being conducted at Chang Gung Memorial Hospital at Chiayi, Taiwan. Ethics and dissemination This trial has been approved by the Institutional Review Board of Chang Gung Memorial Hospital (approval no. 202 002 482A3). Written informed consent will be obtained from all research participants. Study results will be published as peer-reviewed articles. Trial registration number ClinicalTrials.gov, Identifier: NCT05001984; Pre-results.