The Feasibility and Safety of RK-4 Injection Bypassing Blood-brain Barrier in the Treatment of Acute Large Hemispheric Infarction Using Intracalvariosseous Injection Device

Más betegség

• 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;
• Refractory hypertension (systolic \> 200mmHg or diastolic \> 110mmHg) or hypotension (systolic \< 70mmHg or diastolic \< 50mmHg) that is difficult to control with medication;
• 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;
• 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;

Laborértékek

• 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)
• Bleeding tendencies considered by the investigators to be detrimental to the procedure include, but are not limited to, platelet counts \< 100×109/L, and the presence of clotting disorders such as hemophilia;
• Presence of severe or very severe anemia (hemoglobin \<60 g/L) at randomization;

Egyéb

• 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;
• 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.

• 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:
  • 16≤ 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 \<620×10-6mm2/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.