Efficacy and Safety of Early Combined Therapy With PCSK9 Inhibitors and Statins in Acute Ischemic Stroke

NCT06696820 | Recruiting Phase 2 DMC

• 1 other identifier: 1100939
• Study Type: interventional
• Target: 429
• Locations: 1 country
• Sites: 2

Brief Summary

This study is an investigator-initiated, multicenter, prospective, open-label, endpoint-blinded, randomized controlled trial (PROBE design) that includes patients with moderate or severe symptomatic intracranial large vessel atherosclerotic stenosis (sICAS) who present with acute ischemic stroke within 48 hours of symptom onset. Patients will be centrally randomized in a 1:1 ratio into two groups: Experimental Group: A single subcutaneous injection of 420 mg evolocumab upon admission, combined with standard doses of atorvastatin 20 mg or rosuvastatin 10 mg, along with other standard guideline-based medical treatments. Control Group: Standard doses of atorvastatin 20 mg or rosuvastatin 10 mg, with the remainder of treatment based on current guidelines. The primary objective of the study is to evaluate whether early combination therapy with a PCSK9 inhibitor and statins within 48 hours of symptom onset can reduce the incidence of early neurological deterioration in patients with symptomatic intracranial atherosclerotic stenosis (sICAS). The secondary objectives include comparing the effects of early PCSK9 inhibitor and statin combination therapy versus statin monotherapy on the 90-day neurological outcomes of AIS patients, improving early neurological recovery, and reducing the recurrence rate of stroke at 30 and 90 days. The safety objective is to assess whether the combination of early PCSK9 inhibitors and statins, compared to statin monotherapy, increases the incidence of moderate-to-severe systemic bleeding within 3 days post-randomization (based on the GUSTO scale), any type of intracranial hemorrhage (according to the ECASS III criteria), and all-cause mortality within 90 days.

Conditions

Acute Ischemic Stroke

Keywords

Acute Ischemic Stroke; PCSK9 inhibitor

Outcome Measures

Primary Outcomes (2)

• Proportion of early neurological deterioration

  The proportion of patients with an increase of ≥2 points in the NIHSS score from baseline within 3 days post-randomization

  Within 3 days of randomization

• The proportion of moderate-to-severe systemic bleeding within 3 days post-randomization (according to the GUSTO criteria)

  Within 3 days of randomization

Secondary Outcomes (16)

• The proportion of patients with an increase of ≥4 points in the NIHSS score from baseline within 3 days post-randomization

  Within 3 days of randomization

• Proportion of early neurological improvement

  Within 3 days of randomization

• The change in NIHSS score from baseline to 1 day post-randomization.

  One day after randomization

• The change in NIHSS score from baseline to 3 day post-randomization.

  3 day after randomization

• The change in NIHSS score from baseline to 7 day post-randomization.

  7 days after randomization

Study Arms (2)

PCSK9 inhibitors combined with atorvastatin/rosuvastatin

EXPERIMENTAL

Drug: PCSK9 inhibitors combined with atorvastatin/rosuvastatin

Atorvastatin/rosuvastatin

SHAM COMPARATOR

Drug: Atorvastatin/Rosuvastatin

Interventions

Atorvastatin/Rosuvastatin DRUG

Conventional Atorvastatin 20 mg / Rosuvastatin 10 mg

Atorvastatin/rosuvastatin

PCSK9 inhibitors combined with atorvastatin/rosuvastatin DRUG

A single subcutaneous injection of 420 mg Evolocumab upon admission, along with a standard dose of 20 mg Atorvastatin or 10 mg Rosuvastatin

PCSK9 inhibitors combined with atorvastatin/rosuvastatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Acute ischemic stroke diagnosed by CT or MRI of the head.
• Symptom onset to randomization within 48 hours, including wake-up strokes or strokes without a witnessed onset. The time of symptom onset is defined as the "last known normal time."
• NIHSS score ≤ 20.
• mRS score of 0-1 prior to the current stroke.
• Moderate or severe intracranial stenosis or occlusion (≥50%) confirmed by CTA, MRA, or DSA, involving the responsible intracranial arteries: intradural internal carotid artery, M1-2 segments of the middle cerebral artery, A1 segment of the anterior cerebral artery, V4 segment of the vertebral artery, basilar artery, or P1 segment of the posterior cerebral artery.
• The participant or legal representative has signed the informed consent form.

You may not qualify if:

• Cardiogenic embolism (e.g., atrial fibrillation, cardiac valvular disease, etc.).
• Symptomatic intracranial stenosis or occlusion due to arteritis, arterial dissection, moyamoya disease, or other similar conditions.
• Patients who have received intravenous thrombolysis or mechanical thrombectomy.
• Use of PCSK9 inhibitors within the 1 month prior to the onset of the stroke.
• Allergy to statins or PCSK9 inhibitors.
• Active liver disease, including unexplained persistent elevations of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST).
• Known severe renal impairment (creatinine clearance \<30 mL/min).
• Myopathy.
• Concurrent use of cyclosporine.
• Known pregnancy or breastfeeding, or a positive pregnancy test prior to randomization.
• Life expectancy \<3 months (e.g., due to severe cardiopulmonary disease, renal failure, malignancy, or other terminal conditions).
• Participation in other interventional clinical trials that may impact outcome assessments.
• Any other condition that, in the investigator's judgment, makes the patient unsuitable for participation or poses significant risks to the patient.

Sponsors & Collaborators

• Xiang Luo: lead
• Yichang Central People's Hospital: collaborator
• The Fifth Hospital of Wuhan: collaborator
• Wuhan Third Hospital: collaborator
• Shanghai Zhongshan Hospital: collaborator
• Renmin Hospital of Wuhan University: collaborator
• Taihe Hospital: collaborator
• Tianyou Hospital Affiliated to Wuhan University of Science and Technology: collaborator
• Hubei Shiyan People's Hospital: collaborator
• Zigong Fourth People's Hospital: collaborator
• Wuhan No.1 Hospital: collaborator
• Hanyang Hospital, Wuhan University of Science and Technology: collaborator
• Changjiang Shipping General Hospital: collaborator
• Wuhan NO. 4 hospital: collaborator
• Affiliated Renhe Hospital of China Three Gorges University, China: collaborator
• Wuhan Central Hospital: collaborator
• Nanyang Central Hospital of Henan Province: collaborator
• Yichang Yiling Hospital: collaborator
• Mianyang Central Hospital: collaborator
• Xihua People's Hospital: collaborator
• Neijiang No.2 People's Hospital: collaborator
• The Central Hospital of Huanggang: collaborator
• The Tirst People's Hospital of Mianyang: collaborator
• People's Hospital of Dangyang: collaborator
• Chengdu Jingdongfang Hospital: collaborator
• Wuhan Hankou Hospital: collaborator
• Zhongxiang Traditional Chinese Medicine (TCM) Hospital: collaborator
• Sichuan Science City Hospital: collaborator
• The People's Hospital of Huangpi: collaborator
• Ba Zhong Shi Zhong Yi Yi Yuan: collaborator
• Beichuan Qiang Autonomous County People's Hospital: collaborator
• The First People's Hospital of Mianyang: collaborator
• The Third People's Hospital of Hubei Province: collaborator
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: collaborator
• Santai People's Hospital: collaborator
• The General Hospital of Central Theater Command: collaborator
• Minda Hospital of Hubei Minzu University: collaborator

Study Sites (2)

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430030, China

RECRUITING

Tongji Hospital,Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430030, China

NOT YET RECRUITING

Related Publications (1)

• 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: 35143758 RESULT

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Atorvastatin; Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines

Central Study Contacts

Xiang Luo

CONTACT

133349893413; flydottjh@163.com

Yi Xie

CONTACT

13026106657; yixie@tjh.tjmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 17, 2024
• First Posted: November 20, 2024
• Study Start: November 29, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 3, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)