Comparing Y-3 injections in the treatment of large brain strokes

The Efficacy and Safety of Y-3 Intracalvariosseous Injection Bypassing Blood-brain Barrier Versus Intravenous Injection in the Treatment of Acute Large Hemispheric Infarction（SOLUTION-2）

This study is testing a new way to deliver a treatment for large brain strokes to see if it helps patients recover better than the usual method.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 134 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Beijing Tiantan Hospital (Academic / other)
• Locations: 6 sites (Wuhu, Anhui and 5 other locations)
• Trial ID: NCT06374667 on ClinicalTrials.gov

What this trial studies

This trial investigates the efficacy and safety of Y-3 intracalvariosseous (ICO) injection versus intravenous injection in patients suffering from acute large hemispheric infarction (LHI). The study aims to address the limitations of current treatments, particularly for patients who cannot undergo reperfusion therapy. By utilizing a novel drug delivery method that bypasses the blood-brain barrier, the trial seeks to improve functional outcomes in stroke patients. It is a multicentered, prospective, randomized, open-label study designed to provide robust data on the effectiveness of this approach.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 80 who are experiencing their first stroke and have specific neurological deficits within 24 hours of onset.

Not a fit: Patients with contraindications to Y-3 or those who do not meet the eligibility criteria, such as those with prior strokes or severe comorbidities, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve recovery outcomes for patients with large hemispheric infarctions who are not candidates for traditional therapies.

How similar studies have performed: Previous studies have shown promising results with similar neuroprotective approaches, but this specific method of ICO injection is novel.

Eligibility criteria

Inclusion Criteria:

* 18≤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:

  1. 16≤ NIHSS ≤32 points, and the sum of the scores of motor arm and motor leg is ≥6;
  2. 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

Exclusion Criteria:

* Complications with other cerebrovascular diseases meet one of the following conditions:

  1. Complicated with acute cerebral hemorrhage and subarachnoid hemorrhage;
  2. Complicated with acute posterior circulation cerebral infarction or severe posterior circulation stenosis (\>70%);
  3. Or imaging suggests that the area of cerebral infarction is involved bilaterally;
  4. 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；
* Presence of severe or very severe anemia (hemoglobin \<60 g/L) at randomization；
* Patients with severe respiratory diseases (severe chronic obstructive pulmonary disease, respiratory failure, etc.) should be corrected by intubation, tracheotomy, or ventilator;
* The subjects were considered to have developed clinically significant serious infections, including severe local infections or systemic infections;
* Diagnosed severe degenerative diseases of the central nervous system such as Alzheimer's Disease (AD), Parkinson's Disease (PD), and severe dementia of all causes, or psychiatric disorders (e.g., schizophrenia, depression, etc.);
* Subjects with a life expectancy of less than 3 months due to conditions not considered current by the investigators, such as tumors;
* Known allergy to any component of investigational process therapy drugs and contrast agents;
* Subjects who are pregnant, breastfeeding or have the possibility of becoming pregnant or plan to become pregnant;
* Subjects are unable to comply with trial protocols or follow-up requirements;
* Other circumstances deemed by the investigators to be unsuitable for enrollment (registration of reasons for inability to enroll is required);
* Have participated in other interventional clinical trials.

Where this trial is running

Wuhu, Anhui and 5 other locations

• The first affiliated hospital of Wannan Medical College — Wuhu, Anhui, China (Recruiting)
• Beijing Tiantan Hospital — Beijing, Beijing Municipality, 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)

Study contacts

• Principal investigator: Yilong Wang, PhD，MD — Beijing Tiantan Hospital, Capital Medical University, Beijing, China
• Study coordinator: Yilong Wang, PhD+MD

Conditions Stroke, Acute Ischemic; Blood-Brain Barrier; large hemispheric infarction; Y-3; postsynaptic density protein 95 inhibitor; BBB-bypassing route; brain drug delivery; intracalvariosseous injection