The Efficacy and Safety of Y-3 Intracalvariosseous Injection Versus Intravenous Injection in the Treatment of Acute Large Hemispheric Infarction

NCT06374667 | Recruiting DMC

• 1 other identifier: KY2024-071-02
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 6

Brief Summary

A pilot study confirmed the feasibility and safety of neuroprotectant Y-3 intracalvariosseous(ICO) injection in patients with malignant middle cerebral artery infarction (mMCAI), showing a trend in improving 90-day functional scores compared to conventional treatment. The aim of this trial is to further investigate the efficacy and safety of ICO injection of Y-3 compared to intravenous injection in patients with acute large hemispheric infarction(LHI) who has contraindications of reperfusion therapy or have got poor reperfusion therapy outcomes.

Conditions

Stroke, Acute Ischemic; Blood-Brain Barrier

Keywords

large hemispheric infarction; Y-3; postsynaptic density protein 95 inhibitor; BBB-bypassing route; brain drug delivery; intracalvariosseous injection

Outcome Measures

Primary Outcomes (1)

• 90-day favorable clinical outcome

  Favorable clinical outcome defined as a dichotomized mRS 0-3 outcome The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale runs from 0-6 with "0" being perfect health without symptoms to "6" being death. Score 0: No symptoms Score 1: No significant disability. Able to carry out all usual activities, despite some symptoms. Score 2: Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. Score 3: Moderate disability. Requires some help, but able to walk unassisted. Score 4: Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. Score 5: Severe disability. Requires constant nursing care and attention, bedridden, incontinent. Score 6: Dead

  90±7 days after randomization

Secondary Outcomes (7)

• Change of infarct volume from baseline to 8-day

  baseline，8±1 days after randomization

• Neurofunctional deficit defined as the National Institutes of Health Stroke Scale (NIHSS) .

  8±1 days after randomization，14±1 days after randomization，90±7 days after randomization

• Patients with symptoms improvement from baseline to 14-day

  baseline，14±1 days after randomization

• Rate of decompressive hemicraniectomy

  90±7 days after randomization

• Depression scale scores at 90-day

  90±7 days after randomization

Other Outcomes (3)

• 1-year favorable clinical outcome

  1 year±14 days after randomization

• 1-year modified Rankin Scale

  1 year±14 days after randomization

• 1-year anterior circulation Alberta Stroke Program Early CT Score

  1 year±14 days after randomization

Study Arms (2)

ICO injection group

EXPERIMENTAL

Y-3 ICO injection (dose was given as 32 ug/kg) once a day for 3 consecutive days, as well as standard treatment and management according to the related guidelines.

Procedure: Y-3 ICO injection; Other: Conventional treatment

intravenous injection group

ACTIVE COMPARATOR

Y-3 intravenous injection(dose was given as 40mg + 250ml normal saline), as well as standard treatment and management according to related guidelines.

Drug: Y-3 intravenous injection; Other: Conventional treatment

Interventions

Y-3 ICO injection PROCEDURE

Patients included will be given skull outer plate drilling surgery and Y-3 ICO injection under local anesthesia and sedation. The injection will be given for 3 consecutive days.

ICO injection group

Y-3 intravenous injection DRUG

Patients included will be given Y-3 intravenous injection for 7 consecutive days.

intravenous injection group

Conventional treatment OTHER

standard treatment and management according to related guidelines during the entire treatment period

ICO injection group; intravenous injection group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≤Age≤80 years;
• First stroke or complete self-care before the onset of current stroke (mRS 0-1);
• Administration of drugs can be completed within 24h of the onset of signs and symptoms of neurological deficits (in patients with wake-up strokes or unwitnessed strokes, the time of onset is defined as the time of last normal presentation);
• Clinical symptoms, signs and imaging diagnosis of cerebral infarction in the area supplied by the middle cerebral artery, together with the following features:
• ≤ NIHSS ≤32 points, and the sum of the scores of motor arm and motor leg is ≥6;
• Imaging suggestive of core infarct area: apparent diffusion coefficient (ADC) values \<620×10\^-6mm\^2/s lesion volume on magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) sequences or cerebral blood flow (CBF) \<30% of volume 70-300 ml on computed tomography perfusion imaging (CTP) or an Alberta Stroke Program Early CT Score (ASPECTS) of 0-6, with inconsistent findings, the investigator is required to make a reasoned judgement by taking into account all the information (scanning time, the imaging method that best responds to the size of infarct, etc.) and record it.
• NIHSS score not improving or progressing after reperfusion therapy and total score still ≤32.
• Informed consent signed

You may not qualify if:

• Complications with other cerebrovascular diseases meet one of the following conditions:
• Complicated with acute cerebral hemorrhage and subarachnoid hemorrhage;
• Complicated with acute posterior circulation cerebral infarction or severe posterior circulation stenosis (\>70%);
• Or imaging suggests that the area of cerebral infarction is involved bilaterally;
• The cause of the TOAST classification was considered as intracranial artery dissection, vasculitis, moyamoya disease and other etiological types.
• Hemorrhage transformation in the infarction area, hematoma area ≥30% of the infarction area, and has obvious space-occupying effect;
• Presence of clinical signs of brain herniation formation, e.g., unilateral or bilateral pupil dilation and fixation; cerebral oedema-associated loss of consciousness (NIHSS 1a \> 2 points), or other loss of brainstem reflexes in the judgement of the investigator, caused by cerebral oedema or cerebral herniation formation; or other signs of instability of vital signs that are difficult to control;
• Craniotomy decompression was planned before randomization;
• Refractory hypertension (systolic \> 200mmHg or diastolic \> 110mmHg) or hypotension (systolic \< 70mmHg or diastolic \< 50mmHg) that is difficult to control with medication;
• Abnormal blood glucose before randomization (random venous blood glucose \< 2.8mmol/L or \> 23mmol/L);
• Presence of significant abnormal liver function markers or renal function markers prior to randomization;
• Note: Severe liver function abnormalities were defined as serum alanine aminotransferase (ALT), or aspartate aminotransferase (AST) \> 3 times the upper limit of normal (ULN). Significant renal insufficiency is defined as eGFR less than 60 mL/min/1.73 m² (eGFR, calculated using the CKD-EPI formula)
• Acute ST-elevation myocardial infarction (MI) and/or decompensated heart failure (meeting the New York College of Cardiology (NYHA) Heart function grades III and IV) within the past 3 months;
• Presence of contraindications to intracalvariosseous injection, e.g., skull fracture in the last 3 months, skull infection, subdural/extradural hematoma, subcutaneous hematoma, skin or subcutaneous infection of the scalp, poorly displayed skull bone marrow niches；
• Bleeding tendencies considered by the investigators to be detrimental to the procedure include, but are not limited to, platelet counts \< 100×10\^9/L, and the presence of clotting disorders such as hemophilia；

Sponsors & Collaborators

• yilong Wang: lead

Study Sites (6)

The first affiliated hospital of Wannan Medical College

Wuhu, Anhui, China

RECRUITING

Beijing Tiantan Hospital

Beijing, Beijing Municipality, 100050, China

RECRUITING

North China University of Science and Technology Affiliated Hospital

Tangshan, Heibei, China

RECRUITING

Tangshan Municipal Worker's Hospital

Tangshan, Heibei, China

WITHDRAWN

Shaanxi Provincial People's Hospital

Xi'an, Shaanxi, China

RECRUITING

Tianjin Huanhu hospital

Tianjin, China

RECRUITING

Related Publications (1)

• Wang N, Zhang M, Yang M, Liu W, Liu W, Ou Y, Zhou M, Wang X, Sun Z, Pan Y, Wang Y, Wang Y. Efficacy and safety of Y-3 intracalvariosseous injection versus intravenous injection in the treatment of acute large hemispheric infarction (SOLUTION-2): rationale and design of a multicentre, prospective, randomised, open-label, blind endpoint (PROBE) trial. Stroke Vasc Neurol. 2025 Jun 3:svn-2024-004011. doi: 10.1136/svn-2024-004011. Online ahead of print.

  PMID: 40461153 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

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

Study Officials

• Yilong Wang, PhD，MD

  Beijing Tiantan Hospital, Capital Medical University, Beijing, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yilong Wang, PhD+MD

CONTACT

18842627325/13261655100; yilong528@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Vice President of Beijing Tiantan Hospital

Study Record Dates

• First Submitted: April 16, 2024
• First Posted: April 18, 2024
• Study Start: April 22, 2024
• Primary Completion: March 15, 2026
• Study Completion (Estimated): March 15, 2027
• Last Updated: January 28, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (6)