Acute large hemispheric infarction
Conditions
Interventions
low-dose group:Take drug RK-4 (1 mg ) by transcranial bone marrow injection once daily for consecutive 3 days
Medium-dose group:Take drug RK-4 (2 mg ) by transcranial bone marrow injection once daily for consecutive 3 days
High-dose group:Take drug RK-4 (4 mg ) by transcranial bone marrow injection once daily for consecutive 3 days
Sponsors
Beijing Tiantan Hospital, Capital Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 81 Years
Inclusion criteria
Inclusion criteria: 1.18 Age =6; b) Imaging suggests the core area of infarction: Lesions with cerebral blood flow (CBF) less than 30% in computed tomography perfusion imaging (CTP) or with apparent diffusion coefficient (ADC) value less than 620×10-6mm^2/s in diffusion-weighted imaging (DWI) sequences of magnetic resonance imaging (MRI) ranging from 70 to 300ml or with ASPECTS score ranging from 0 to 6 points. Give priority to the results of CTP examination. If both CTP and DWI are completed during the screening period and the examination results are inconsistent, the researcher needs to make a reasonable judgment by comprehensively considering all information (scanning time, the imaging method that best reflects the size of infarction, etc.) and record it. The ASPECTS score can be based on either CTP or MRI, but CTP is preferred. 5. If vascular reperfusion therapy is performed, the therapeutic effect will be poor, and the following conditions must be met simultaneously: a) Extended thrombolysis grade for Cerebral infarction (eTICI) =2a; b) After vascular reperfusion treatment, the NIHSS score did not improve or progress, and the total score was still <=32 points. Note: A reduction of 1 point or more indicates improvement, while an increase of 1 point or more indicates progress. 6. The subject or his/her legal representative voluntarily signs the informed consent form.
Exclusion criteria
Exclusion criteria: Concurrent other cerebrovascular diseases meet one of the following conditions: a) Combined with acute cerebral hemorrhage and subarachnoid hemorrhage; b) Combined with acute posterior circulation cerebral infarction, or severe stenosis of posterior circulation vessels (> 70%); c) Imaging suggests that the cerebral infarction area involves both sides; d) Before screening, the etiology was clearly diagnosed as intracranial arterial dissection, vasculitis, Moyamoya disease or other etiological types through TOAST classification. 2. Hemorrhage transformation in the infarcted area, with hematoma area >=30% of the infarcted area, and a significant space-occupying effect; 3. There are clinical signs of brain herniation, for example, unilateral or bilateral pupil dilation and fixation; Loss of consciousness related to brain edema (NIHSS 1a > 2 points), or other brainstem reflex losses determined by researchers to be caused by brain edema or brain herniation formation; Or other uncontrollable signs of unstable vital signs; 4. When screening, it is planned to perform craniectomy and decompressive craniectomy. 5. Intractable hypertension (systolic blood pressure > 200mmHg or diastolic blood pressure > 110mmHg) or hypotension (systolic blood pressure 23mmol/L); 7. There are obvious abnormalities in liver function indicators or obvious abnormalities in renal function indicators; Note: Obvious abnormal liver function indicators refer to serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) being greater than three times the upper limit of the normal value (ULN). Obvious abnormal renal function indicators refer to eGFR less than 60 mL/min/1.73 m^2 (eGFR is calculated using the CKD-EPI formula). 8. Within the past three months, acute ST-segment elevation myocardial infarction (MI) and/or acute decompensated heart failure occurred [conforming to the New York Heart Association (NYHA) cardiac function classification of grade III or IV)]; 9. There are contraindications for administration through the skull and bone marrow, such as skull fractures within the last 3 months, skull infections, subdural/epidural hematoma, subcutaneous hematoma of the scalp, scalp skin or subcutaneous infections, and unclear display of the skull board, etc. 10. Bleeding tendencies that researchers consider unfavorable for the operation include but are not limited to: platelet count 38.5?), increased heart rate, chills, consciousness disorders, breathing difficulties, shock, etc. caused by infection; 14. Confirmed severe CNS degenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and severe dementia caused by various reasons, or suffering
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the safety of transcranial bone marrow injection of RK-4 injection in the treatment of patients with acute large cerebral hemisphere infarction on the 14th +/- 1st day of treatment (adverse events and changes in laboratory test data before and after treatment);To evaluate the tolerance of RK-4 injection through cranial bone marrow on the 14th +/- 1st day of treatment in subjects with acute large cerebral hemisphere infarction (changes in adverse events and laboratory test data before and after treatment); | — |
Secondary
| Measure | Time frame |
|---|---|
| Evaluate the pharmacokinetic characteristics of single ascending doses of RK-4 in patients with LHI by venous blood;Evaluate the efficacy of RK-4 in patients with LHI by the proportion of NIHSS score improvement of >=8 points from baseline on the 14th +/-1 day of treatment;Evaluate the efficacy of RK-4 in patients with LHI by the proportion of NIHSS score improvement of >=4 points from baseline on the 14th +/-1 day of treatment;The changes of NIHSS scores from baseline on the 4th +/-1 day, 8th +/-1 day, and 14th +/-1 day of treatment; | — |
Countries
China
Contacts
Public ContactWang Yilong
Beijing Tiantan Hospital, Capital Medical University
Outcome results
None listed