Ignite Creation Date:
2026-03-26 @ 3:18 PM
Ignite Modification Date:
2026-03-30 @ 4:36 AM
Study NCT ID:
NCT07466251
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-03-12
First Post:
2026-03-07
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
PCSK9 Inhibitor for Intracranial Atherosclerosis Related Acute Ischemic Stroke
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D058226', 'term': 'Plaque, Atherosclerotic'}, {'id': 'D002537', 'term': 'Intracranial Arteriosclerosis'}], 'ancestors': [{'id': 'D020763', 'term': 'Pathological Conditions, Anatomical'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D020765', 'term': 'Intracranial Arterial Diseases'}, {'id': 'D002561', 'term': 'Cerebrovascular Disorders'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D001161', 'term': 'Arteriosclerosis'}, {'id': 'D001157', 'term': 'Arterial Occlusive Diseases'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D059039', 'term': 'Standard of Care'}], 'ancestors': [{'id': 'D019984', 'term': 'Quality Indicators, Health Care'}, {'id': 'D011787', 'term': 'Quality of Health Care'}, {'id': 'D006298', 'term': 'Health Services Administration'}, {'id': 'D017530', 'term': 'Health Care Quality, Access, and Evaluation'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR'], 'maskingDescription': 'Subjects, clinical investigators, outcome assessors, imaging evaluators, laboratory technicians, data management personnel, and statistical analysts remained blinded to treatment allocation throughout the entire study.'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 1212}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-09-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-03', 'completionDateStruct': {'date': '2029-12-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-03-11', 'studyFirstSubmitDate': '2026-03-07', 'studyFirstSubmitQcDate': '2026-03-11', 'lastUpdatePostDateStruct': {'date': '2026-03-12', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-03-12', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-12-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'NIHSS at 24 hours, 7 days, and discharge', 'timeFrame': 'At 24 hours, 7 days, and at discharge', 'description': 'Assessment using the National Institutes of Health Stroke Scale'}, {'measure': 'Cerebral infarction volume or perfusion status at 7 days post-enrollment or at discharge', 'timeFrame': 'At 7 days post-enrollment or upon discharge', 'description': 'Evaluate using CT/CTP or MRI/PWI'}, {'measure': 'Inflammation levels at 7 days post-group assignment or at discharge', 'timeFrame': 'At 7 days post-enrollment or upon discharge', 'description': 'Evaluated through markers such as interleukin IL-6 and high-sensitivity C-reactive protein'}, {'measure': 'The proportion of subjects with moderate to severe symptomatic intracranial hemorrhage(sICH)', 'timeFrame': 'From randomization to Day 90 of enrollment', 'description': 'The diagnosis of symptomatic intracranial hemorrhage will be assessed based on the modified Heidelberg hemorrhage classification criteria, requiring simultaneous fulfillment of the following conditions:\n\n1. Imaging confirmation of any of the following types of intracranial hemorrhage: parenchymal hemorrhage type 1, parenchymal hemorrhage type 2, distant intracranial hemorrhage, subarachnoid hemorrhage, intraventricular hemorrhage, or subdural hemorrhage;\n2. An increase in total NIHSS score of ≥4 points compared to baseline NIHSS or any previously recorded NIHSS score;\n3. Symptom deterioration cannot be explained by causes other than the intracranial hemorrhage itself.'}, {'measure': 'Adverse events', 'timeFrame': 'From randomization to Day 90 of enrollment', 'description': 'An Adverse Event (AE) is any untoward medical occurrence in clinical trial subject administered a pharmaceutical product and which does not necessarily have a causal relationship with the treatment.'}, {'measure': 'Serious Adverse Events', 'timeFrame': 'From randomization to Day 90 of enrollment', 'description': 'A Serious Adverse Event (SAE) is any untoward medical occurrence that, at any dose: (1) results in death; (2) is life-threatening; (3) requires inpatient hospitalization or prolongation of existing hospitalization; (4)results in persistent or significant disability/incapacity; (5) is a congenital anomaly/birth defect; (6) is otherwise considered medically significant by the investigator.'}], 'primaryOutcomes': [{'measure': '90-day modified Rankin Scale (mRS) score of 0-2', 'timeFrame': 'Day 90 of patient enrollment', 'description': 'Scoring using the modified Rankin Scale (mRS)'}], 'secondaryOutcomes': [{'measure': '90-day modified Rankin Scale (mRS) score of 0-1', 'timeFrame': 'Day 90 of patient enrollment', 'description': 'Scoring using the modified Rankin Scale (mRS)'}, {'measure': 'Distribution of modified Rankin Scale (mRS) scores at 90 days', 'timeFrame': 'Day 90 of patient enrollment', 'description': 'Scoring using the modified Rankin Scale (mRS)'}, {'measure': 'Time from randomization to the first-ever stroke', 'timeFrame': 'From randomization to Day 90 of enrollment', 'description': "Stroke is a general term for acute cerebrovascular diseases, referring to brain tissue damage or death caused by rupture or blockage of intracranial blood vessels due to various causes. It can be classified into two major categories: hemorrhagic and ischemic, as determined by the project's Clinical Events Committee."}, {'measure': 'Time from randomization to the first-ever ischemic stroke', 'timeFrame': 'From randomization to Day 90 of enrollment', 'description': 'Ischemic Stroke: Defined as an acute cerebral infarction with clinical signs or imaging evidence of a new acute focal neurological injury persisting for more than 24 hours, excluding other non-ischemic causes.'}, {'measure': 'Time from randomization to the occurrence of major adverse cardiovascular events', 'timeFrame': 'From randomization to Day 90 of enrollment', 'description': 'Composite major adverse cardiovascular endpoints includes ischemic stroke, myocardial infarction, and cardiovascular mortality as a cluster'}, {'measure': 'Barthel Index (BI) Score', 'timeFrame': 'On Day 90 and at 1 year after enrollment', 'description': 'Scoring using the Barthel Index (BI) for activities of daily living'}, {'measure': 'European Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) Score', 'timeFrame': 'On Day 90 and at 1 year after enrollment', 'description': 'Scoring using the European Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L)'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Intracranial Atherosclerosis', 'intracranial artery stenosis', 'atherosclerotic plaque', 'PCSK9 inhibitor', 'Recaticimab'], 'conditions': ['Acute Ischemic Stroke AIS', 'Intracranial Atherosclerosis ICAS', 'Atherosclerotic Plaque']}, 'referencesModule': {'references': [{'pmid': '38648030', 'type': 'RESULT', 'citation': 'Zhao W, Li S, Li C, Wu C, Wang J, Xing L, Wan Y, Qin J, Xu Y, Wang R, Wen C, Wang A, Liu L, Wang J, Song H, Feng W, Ma Q, Ji X; TREND Investigators. Effects of Tirofiban on Neurological Deterioration in Patients With Acute Ischemic Stroke: A Randomized Clinical Trial. JAMA Neurol. 2024 Jun 1;81(6):594-602. doi: 10.1001/jamaneurol.2024.0868.'}, {'pmid': '40616232', 'type': 'RESULT', 'citation': 'Tao C, Liu T, Cui T, Liu J, Li Z, Ren Y, Zhao X, Xie F, Li J, Wang H, Huang L, Li J, Wen J, Zeng J, Zhu J, Li Z, Li D, Hu X, Huang B, Wang J, Zhang C, Ye B, Hou Y, Gan Y, Sun H, Guan F, Shao Y, Liu Z, Ou Z, Fan S, Wang Y, Zhai H, Ni C, Wang H, Zhang C, Zhao Y, Wang G, Zhu Y, Li R, Sun J, Hu H, Cui J, Wang L, Zhang C, Song J, Jing X, Wang A, Wang J, Xu P, Qureshi AI, Nguyen TN, Nogueira RG, Saver JL, Hu W; ASSET-IT Investigators. Early Tirofiban Infusion after Intravenous Thrombolysis for Stroke. N Engl J Med. 2025 Sep 25;393(12):1191-1201. doi: 10.1056/NEJMoa2503678. Epub 2025 Jul 4.'}, {'pmid': '41500725', 'type': 'RESULT', 'citation': 'Wang C, Gu H, Huo X, Yuan B, Li S, Xu J, Jiang Y, Jing J, Yao X, Li Z, Long F, Ma Z, Zhuang X, Xu L, Jin Y, Huang W, Zhang Y, Wen J, Wang A, Pan Y, Ye W, Yu W, Cheng A, Wang M, Dong Q, Xu A, Wang N, Yang Y, Meng X, Liu L, Zhao X, Li H, Miao Z, Li Z, Wang Y; TASTE-2 investigators. Edaravone dexborneol versus placebo on functional outcomes in patients with acute ischaemic stroke undergoing endovascular thrombectomy (TASTE-2): randomised controlled trial. BMJ. 2026 Jan 7;392:e086850. doi: 10.1136/bmj-2025-086850.'}, {'type': 'RESULT', 'citation': 'Investigators WCftP, investigators P. Intra-Arterial Alteplase After Successful Endovascular Reperfusion in Acute Stroke: The PEARL Randomized Clinical Trial. JAMA. 2025;334(19):1728-1739. doi:10.1001/jama.2025.16876'}, {'pmid': '38817546', 'type': 'RESULT', 'citation': 'Kim J, Hong U, Yoon CW, Bae JW, Rha JH, Park HK. PCSK9 inhibitor in acute ischemic stroke patient receiving mechanical thrombectomy: early outcomes and safety. Front Neurol. 2024 May 16;15:1375609. doi: 10.3389/fneur.2024.1375609. eCollection 2024.'}, {'pmid': '32561535', 'type': 'RESULT', 'citation': 'Liu L, Chen W, Zhou H, Duan W, Li S, Huo X, Xu W, Huang L, Zheng H, Liu J, Liu H, Wei Y, Xu J, Wang Y; Chinese Stroke Association Stroke Council Guideline Writing Committee. Chinese Stroke Association guidelines for clinical management of cerebrovascular disorders: executive summary and 2019 update of clinical management of ischaemic cerebrovascular diseases. Stroke Vasc Neurol. 2020 Jun;5(2):159-176. doi: 10.1136/svn-2020-000378. Epub 2020 Jun 18.'}, {'pmid': '41582814', 'type': 'RESULT', 'citation': 'Prabhakaran S, Gonzalez NR, Zachrison KS, Adeoye O, Alexandrov AW, Ansari SA, Chapman S, Czap AL, Dumitrascu OM, Ishida K, Jadhav AP, Johnson B, Johnston KC, Khatri P, Kimberly WT, Lee VH, Leslie-Mazwi TM, Mac Grory B, Madsen TE, Menon B, Mistry EA, Park S, Parker S, Perez de la Ossa N, Reeves M, Saiz T, Scott PA, Schwartzberg D, Sheth SA, Sporns PB, Times S, Tjoumakaris S, Wolfe SQ, Yaghi S; Peer Review Committee. 2026 Guideline for the Early Management of Patients With Acute Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2026 Jan 26. doi: 10.1161/STR.0000000000000513. Online ahead of print.'}, {'pmid': '39505412', 'type': 'RESULT', 'citation': 'Sun Y, Lv Q, Guo Y, Wang Z, Huang R, Gao X, Han Y, Yao Z, Zheng M, Luo S, Li Y, Gu X, Zhang Y, Wang J, Hong L, Ma X, Su G, Sheng J, Lai C, Shen A, Wang M, Zhang W, Wu S, Zheng Z, Li J, Zhong T, Wang Y, He L, Du X, Ma CS. Recaticimab as Add-On Therapy to Statins for Nonfamilial Hypercholesterolemia: The Randomized, Phase 3 REMAIN-2 Trial. J Am Coll Cardiol. 2024 Nov 12;84(20):2037-2047. doi: 10.1016/j.jacc.2024.09.012.'}, {'pmid': '39387764', 'type': 'RESULT', 'citation': 'Xu M, Wang Z, Zhang Y, Liu Y, Huang R, Han X, Yao Z, Sun J, Tian F, Hu X, Ma L, Lai C, Zhang X, Sheng J, Han Q, Jin C, Luo L, Zhao R, Li L, Xu B, Yin D, Luo S, Ge X, Liu Z, Yang P, Huang Z, Li T, Feng W, Wu Y, Ling Z, Ma L, Lv C, Deng C, Wei W, Wang Y, Yan L, Ge J; REMAIN-1 Investigators. Recaticimab Monotherapy for Nonfamilial Hypercholesterolemia and Mixed Hyperlipemia: The Phase 3 REMAIN-1 Randomized Trial. J Am Coll Cardiol. 2024 Nov 12;84(20):2026-2036. doi: 10.1016/j.jacc.2024.07.035. Epub 2024 Oct 9.'}, {'pmid': '41107765', 'type': 'RESULT', 'citation': 'Liu J, Li Y, Tian W, Cao H, Li X, Cheng L, Ji X, Liu J. Effects of PCSK9 inhibitor evolocumab on preventing early neurological deterioration in acute ischemic stroke patients with or without large artery atherosclerosis: a subgroup analysis of a randomized trial. BMC Neurol. 2025 Oct 17;25(1):431. doi: 10.1186/s12883-025-04434-8.'}, {'pmid': '38212060', 'type': 'RESULT', 'citation': 'Wu L, Zhang B, Li C, Zhuang Z, Liu K, Chen H, Zhu S, Zhu J, Dai Z, Huang H, Jiang Y. PCSK9 inhibitors reduced early recurrent stroke in patients with symptomatic intracranial atherosclerotic stenosis. J Neurol Neurosurg Psychiatry. 2024 May 14;95(6):529-535. doi: 10.1136/jnnp-2023-332392.'}, {'pmid': '39755915', 'type': 'RESULT', 'citation': 'Tian W, Cao H, Li X, Gong X, Yu X, Li D, Xie J, Bai Y, Zhang D, Li X, Xu P, Liu J, Zhang B, Ji X, Dong H. Adjunctive PCSK9 Inhibitor Evolocumab in the Prevention of Early Neurological Deterioration in Non-cardiogenic Acute Ischemic Stroke: A Multicenter, Prospective, Randomized, Open-Label, Clinical Trial. CNS Drugs. 2025 Feb;39(2):197-208. doi: 10.1007/s40263-024-01145-5. Epub 2025 Jan 5.'}, {'pmid': '39818872', 'type': 'RESULT', 'citation': 'Zeng W, Zhou F, Zhao H, Wang Y, Chen J, Lu J, Zheng D, Kuang J, Yuan D, Zhou J, Shi C, Zhao X, Leng X, Yan B, Tan Z. Evaluation of Intensive Statins and Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors on Intracranial Artery Plaque Stability: A Prospective Single-Arm Study. J Am Heart Assoc. 2025 Jan 21;14(2):e035651. doi: 10.1161/JAHA.124.035651. Epub 2025 Jan 17.'}, {'pmid': '40820974', 'type': 'RESULT', 'citation': 'Hu X, Liu Y, Yuan W, Zhang Z, Li S, Cheng A, Yu Q, Guo H, Zou Y, Li M, Liu C, Xu Y, Xu W. Evolocumab Added to Statin Is Associated With Intracranial Atherosclerotic Plaque Regression Compared With Statin Alone. J Am Heart Assoc. 2025 Aug 19;14(16):e041251. doi: 10.1161/JAHA.124.041251. Epub 2025 Aug 18.'}, {'pmid': '31707788', 'type': 'RESULT', 'citation': 'Jukema JW, Zijlstra LE, Bhatt DL, Bittner VA, Diaz R, Drexel H, Goodman SG, Kim YU, Pordy R, Reiner Z, Roe MT, Tse HF, Montenegro Valdovinos PC, White HD, Zeiher AM, Szarek M, Schwartz GG, Steg PG; ODYSSEY OUTCOMES Investigators. Effect of Alirocumab on Stroke in ODYSSEY OUTCOMES. Circulation. 2019 Dec 17;140(25):2054-2062. doi: 10.1161/CIRCULATIONAHA.119.043826. Epub 2019 Nov 11.'}, {'pmid': '28304224', 'type': 'RESULT', 'citation': 'Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Wasserman SM, Sever PS, Pedersen TR; FOURIER Steering Committee and Investigators. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017 May 4;376(18):1713-1722. doi: 10.1056/NEJMoa1615664. Epub 2017 Mar 17.'}, {'pmid': '30066942', 'type': 'RESULT', 'citation': 'Wang L, Wang Z, Shi J, Jiang Q, Wang H, Li X, Hao D. Inhibition of proprotein convertase subtilisin/kexin type 9 attenuates neuronal apoptosis following focal cerebral ischemia via apolipoprotein E receptor 2 downregulation in hyperlipidemic mice. Int J Mol Med. 2018 Oct;42(4):2098-2106. doi: 10.3892/ijmm.2018.3797. Epub 2018 Jul 31.'}, {'pmid': '38048667', 'type': 'RESULT', 'citation': 'Zheng Y, Zhu T, Li G, Xu L, Zhang Y. PCSK9 inhibitor protects against ischemic cerebral injury by attenuating inflammation via the GPNMB/CD44 pathway. Int Immunopharmacol. 2024 Jan 5;126:111195. doi: 10.1016/j.intimp.2023.111195. Epub 2023 Dec 4.'}, {'pmid': '39548030', 'type': 'RESULT', 'citation': 'Luo Y, Yuan L, Liu Z, Dong W, Huang L, Liao A, Xie Y, Liu R, Lan W, Cai Y, Zhu W. Inhibition of PCSK9 Protects against Cerebral Ischemia-Reperfusion Injury via Attenuating Microcirculatory Dysfunction. Neurochem Res. 2024 Nov 16;50(1):10. doi: 10.1007/s11064-024-04272-z.'}, {'pmid': '35048716', 'type': 'RESULT', 'citation': 'Punch E, Klein J, Diaba-Nuhoho P, Morawietz H, Garelnabi M. Effects of PCSK9 Targeting: Alleviating Oxidation, Inflammation, and Atherosclerosis. J Am Heart Assoc. 2022 Feb;11(3):e023328. doi: 10.1161/JAHA.121.023328. Epub 2022 Jan 20.'}, {'pmid': '35143758', 'type': 'RESULT', 'citation': 'Gutierrez J, Turan TN, Hoh BL, Chimowitz MI. Intracranial atherosclerotic stenosis: risk factors, diagnosis, and treatment. Lancet Neurol. 2022 Apr;21(4):355-368. doi: 10.1016/S1474-4422(21)00376-8. Epub 2022 Feb 7.'}, {'pmid': '32817184', 'type': 'RESULT', 'citation': 'Park TH, Lee JK, Park MS, Park SS, Hong KS, Ryu WS, Kim DE, Park MS, Choi KH, Kim JT, Kang J, Kim BJ, Han MK, Lee J, Cha JK, Kim DH, Kim JG, Lee SJ, Cho YJ, Kwon JH, Shin DI, Yeo MJ, Sohn SI, Hong JH, Lee JS, Choi JC, Kim WJ, Lee BC, Yu KH, Oh MS, Park JM, Kang K, Lee KB, Lee J, Gorelick PB, Bae HJ. Neurologic deterioration in patients with acute ischemic stroke or transient ischemic attack. Neurology. 2020 Oct 20;95(16):e2178-e2191. doi: 10.1212/WNL.0000000000010603. Epub 2020 Aug 14.'}, {'pmid': '41389830', 'type': 'RESULT', 'citation': 'Glavan M, Liu J, Sampaio Silva G, Nguyen TN, Zhou J, Sestan N, Kimberly WT, Sheth KN. Endovascular thrombectomy for acute stroke: evolving eligibility criteria and adjunct therapies. Lancet Neurol. 2026 Jan;25(1):61-76. doi: 10.1016/S1474-4422(25)00356-4.'}, {'type': 'RESULT', 'citation': '《中国卒中中心报告》编写组. 《中国卒中中心报告 2020》概要.中国脑血管病杂志. 2021;18(11):737-743.'}]}, 'descriptionModule': {'briefSummary': 'This study is a prospective, multicenter, double-blind, randomized, placebo-controlled clinical trial designed to evaluate whether early administration of PCSK9 inhibitors can effectively improve functional outcomes at 90 days in patients with ischemic stroke (AIS) associated with intracranial atherosclerotic stenosis (ICAS), primarily assessed using the modified Rankin Scale at 90 days.', 'detailedDescription': 'Acute ischemic stroke (AIS) remains one of the leading causes of death and disability worldwide. Although intravenous thrombolysis and endovascular therapies have significantly improved reperfusion success rates, three critical challenges persist in clinical practice that determine prognosis: First, only a limited proportion of patients can actually receive reperfusion therapy within the therapeutic time window; Second, even with successful reperfusion, secondary injuries such as microcirculatory perfusion failure, inflammatory cascades, and thrombus reformation may still occur. Third, acute phase fluctuations, particularly early neurological deterioration and the risk of early recurrence, remain prominent, directly limiting improvements in functional outcomes. 3 Intracranial atherosclerotic stenosis (ICAS) accounts for up to 50% of ischemic stroke etiologies in China. Its pathological chain-"plaque instability-thrombosis-microcirculatory impairment"-permeates both the acute and subacute phases, closely correlating with early recurrence and poor outcomes.Proprotein convertase subtilisin/kexin type 9 (PCSK9) classically promotes the degradation of low-density lipoprotein cholesterol (LDL-C) receptors and elevates LDL-C levels, thereby driving atherosclerosis progression. More importantly, growing basic and translational research suggests that PCSK9 may not only function as a "lipid metabolism protein" but also participate in processes such as endothelial activation, inflammatory cascades, platelet reactivity, and microcirculatory dysfunction. This positions it as a potential hub connecting the "plaque-thrombus-inflammation" axis. Consequently, PCSK9 inhibitors may offer additional neurovascular protective benefits beyond lipid-lowering effects during the acute phase of acute ischemic stroke (AIS).Existing basic and clinical evidence suggests that PCSK9 inhibitors may exert a combined intervention effect on key pathological processes driving atherosclerosis during the acute phase of AIS through a dual mechanism involving both lipid-dependent and non-lipid-dependent pathways. Mechanistic studies reveal that PCSK9 inhibition simultaneously modulates inflammatory responses, endothelial activation, dysfunction, and thrombogenic tendencies. In ischemia-reperfusion models, it demonstrates neuroprotective signaling by mitigating brain injury and improving neurological function. Clinically, large randomized trials confirm its ability to rapidly enhance lipid-lowering effects beyond statins and reduce ischemic stroke risk. Further translational evidence in cerebrovascular disease indicates that in symptomatic ICAS populations, PCSK9 inhibitor plus statin-enhanced lipid-lowering therapy reduces plaque burden, alleviates stenosis, and increases plaque stability. In the acute phase of AIS, early addition of PCSK9 inhibitors correlates with reduced neurological deterioration within 7 days, decreased recurrence risk within 30 days, and improved functional outcomes at 90 days. Collectively, this evidence chain spanning mechanisms to clinical practice provides clear scientific rationale and clinical necessity for adding PCSK9 inhibitors to the treatment of ICAS-associated AIS.This study is a nationwide, prospective, multicenter, double-blind, randomized, placebo-controlled clinical trial. It will enroll 1,212 patients meeting inclusion and exclusion criteria. Patients will be randomly assigned to two groups using a randomized allocation method: (1) Experimental group: 450 mg of Recaticimab for Injection (3 vials) administered as a single subcutaneous injection. (2) Control group: Placebo of Recaticimab for Injection 450 mg (3 vials) administered as a single subcutaneous injection. Each group will include 606 patients. Both groups will receive standard guideline-recommended treatment in addition to the study drug. Long-term efficacy was assessed through patient visits and evaluations at 0 hours, 24 hours (±2 or ±12 hours), 7 days (±2 days) or at discharge, 90 days (±7 days), and 1 year.Primary outcome measures included: Analysis based on the intention-to-treat principle using an ANCOVA model for all randomized patients with baseline HRMRI and a modified Rankin Scale (mRS) score of 0-2 at 90 days. Secondary outcome measures included: (1) mRS score of 0-1 at 90 days (indicating good patient function); (2) Distribution of 90-day mRS scores; (3) Any stroke (including ischemic and hemorrhagic) within 90 days; (4) Ischemic stroke within 90 days; (5) Composite vascular events (including stroke, myocardial infarction, and vascular death) within 90 days; (6) 90-day European Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) score; (7) 90-day Barthel Index (BI) score.Details are provided in the "Outcome Measures" section.The sample size is calculated based on the primary outcome and a total of 1212 participants are anticipated. An independent Data Safety Monitoring Board will oversee the overall conduct of the trial.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '30 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age \\>=30 and \\<=80;2.Acute ischemic stroke within 72 hours of onset (as determined by CT/MRI in conjunction with neurological deficit symptoms)\n* Acute ischemic stroke within 72 hours of onset (diagnosed by CT/MRI in conjunction with neurological deficit symptoms)\n* NIHSS score of 4-25 at admission\n* Imaging studies (CTA/DSA/MRA) support intracranial atherosclerosis as the cause of stroke, meeting one of the following criteria: i. The culprit vessel exhibits intracranial atherosclerotic stenosis (ICAS) with a narrowing degree of 50-99%; ii. The culprit vessel exhibits intracranial atherosclerotic occlusion (ICAS-LVO), with successful recanalization achieved via mechanical thrombectomy (immediate expanded thrombolysis in cerebral infarction \\[eTICI\\] grade 2b50-3)\n* Informed consent signed\n\nExclusion Criteria:\n\n* Non-atherosclerotic intracranial arterial stenosis (such as arterial dissection, Moyamoya disease, systemic vasculitis, etc.)\n* Any identifiable source of cardiogenic embolism (such as atrial fibrillation, mechanical valves, left ventricular thrombus, patent foramen ovale, etc.)\n* Imaging findings and clinical presentation suggest that the primary pathophysiology of this event is more consistent with cerebral small vessel disease (e.g., perforator artery occlusion/lacunar infarction)\n* Pre-existing disability prior to this ischemic event (modified Rankin Scale ≥ 2 points)\n* CT or MRI findings suggest extensive cerebral infarction (e.g., ASPECTS score \\< 6 or infarct volume ≥ 70 ml)\n* Has undergone or is scheduled to undergo a vascular stent implantation procedure within the next three months\n* Any intracranial hemorrhage occurring within 3 months prior to enrollment;\n* Intracranial tumors, cerebral aneurysms, or arteriovenous malformations that are assessed as having indications for interventional treatment\n* Severe active bleeding tendency or coagulation disorder\n* Severe dysfunction of vital organs such as the heart, liver, and kidneys\n* Received PCSK9 monoclonal antibody inhibitor therapy within 1 month prior to enrollment or PCSK9 siRNA inhibitor therapy within 6 months prior to enrollment\n* A clear contraindication to statins or a history of intolerance to them\n* Pregnancy, breastfeeding, or planning pregnancy;14.Currently participating in another study'}, 'identificationModule': {'nctId': 'NCT07466251', 'acronym': 'PISTIAS-3', 'briefTitle': 'PCSK9 Inhibitor for Intracranial Atherosclerosis Related Acute Ischemic Stroke', 'organization': {'class': 'OTHER', 'fullName': 'Peking Union Medical College Hospital'}, 'officialTitle': 'PCSK9 Inhibitor for Intracranial Atherosclerosis Related Acute Ischemic Stroke (PISTIAS-3): a Randomized, Double-blind, Placebo-controlled Trial', 'orgStudyIdInfo': {'id': '1-24PJ2600'}, 'secondaryIdInfos': [{'id': '2024ZD0521605', 'type': 'OTHER_GRANT', 'domain': 'the Noncommunicable Chronic Diseases-National Science and Technology Major Project'}, {'id': '82025013', 'type': 'OTHER_GRANT', 'domain': 'the National Science Fund for Distinguished Young Scholars'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Recaticimab plus standard therapy group', 'description': 'Recaticimab in combination with standard therapy', 'interventionNames': ['Drug: Rucacuzumab plus standard therapy']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Recaticimab plus placebo in combination with standard therapy grop', 'description': 'Recaticimab plus placebo in combination with standard therapy', 'interventionNames': ['Drug: Recaticimab plus placebo in combination with standard therapy']}], 'interventions': [{'name': 'Rucacuzumab plus standard therapy', 'type': 'DRUG', 'description': 'Recaticimab (450 mg single dose, subcutaneous injection) combined with standard therapy recommended by the AHA/ASA Guidelines for Early Management of Acute Ischemic Stroke 2026 and the Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke 2023.', 'armGroupLabels': ['Recaticimab plus standard therapy group']}, {'name': 'Recaticimab plus placebo in combination with standard therapy', 'type': 'DRUG', 'description': 'The placebo and investigational ricaximab were identical in appearance, packaging, labeling, administration method, and dosing frequency, managed through a unified production and coding system. Standard treatment followed the recommendations outlined in the "AHA/ASA Guidelines for the Early Management of Acute Ischemic Stroke 2026" and the "Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2023."', 'armGroupLabels': ['Recaticimab plus placebo in combination with standard therapy grop']}]}, 'contactsLocationsModule': {'locations': [{'zip': '100853', 'city': 'Beijing', 'state': 'Beijing Municipality', 'country': 'China', 'contacts': [{'name': 'Shiwen Wu, MD', 'role': 'CONTACT', 'email': 'wu_shiwen@outlook.com', 'phone': '86+13910238117'}, {'name': 'Shiwen Wu, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Chinese PLA General Hospital', 'geoPoint': {'lat': 39.9075, 'lon': 116.39723}}, {'city': 'Meizhou', 'state': 'Guangdong', 'country': 'China', 'facility': 'The Third Affiliated Hospital of Sun Yat-sen University, Yuedong Hospital', 'geoPoint': {'lat': 24.28859, 'lon': 116.11768}}, {'city': 'Cangzhou', 'state': 'Hebei', 'country': 'China', 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'country': 'China', 'facility': 'Chongqing General Hospital', 'geoPoint': {'lat': 29.56026, 'lon': 106.55771}}, {'city': 'Shanghai', 'country': 'China', 'facility': 'Huashan Hospital, Fudan University', 'geoPoint': {'lat': 31.22222, 'lon': 121.45806}}], 'centralContacts': [{'name': 'Weihai Xu, MD', 'role': 'CONTACT', 'email': 'xuwh@pumch.cn', 'phone': '86+13938912070'}, {'name': 'Yiyang Liu, PhD', 'role': 'CONTACT', 'email': 'liuyydoct@163.com', 'phone': '86+13938912070'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Peking Union Medical College Hospital', 'class': 'OTHER'}, 'collaborators': [{'name': 'Chinese PLA General Hospital', 'class': 'OTHER'}, {'name': 'Hebei General Hospital', 'class': 'OTHER'}, {'name': 'Taihe Hospital', 'class': 'OTHER'}, {'name': "Weifang People's Hospital", 'class': 'OTHER'}, {'name': 'Nanjing First Hospital, Nanjing Medical University', 'class': 'OTHER'}, {'name': 'Baotou Central 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