Y-3 Injection Through Skull Bone Marrow in the Treatment of Acute Malignant Middle Cerebral Artery Infarction (SOLUTION)

NCT05849805 | Completed DMC

• 1 other identifier: KY2023-052-02
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The mortality of malignant middle cerebral artery infarction (mMCAI) is up to 80%, while current available treatment is limited. The purpose of this study is to explore the feasibility, safety and efficacy of Intracalvaria bone marrow injection of cytoprotective drug Y-3 in mMCAI patients with contradictions of reperfusion therapy or poor reperfusion outcome.

Conditions

Stroke, Acute Ischemic

Keywords

malignant middle cerebral artery infarction; Y-3; postsynaptic density protein 95 inhibitor; BBB-bypassing route; brain drug delivery; Intracalvaria bone marrow injection

Outcome Measures

Primary Outcomes (12)

• Failed of drilling

  The rate of the internal plate of skull was drilled through

  during 3 days of treatment

• Number of drug-leakage events

  Number of drug-leakage events

  during 3 days of treatment

• Patients' tolerance of therapy

  The number of patient who refused to continue the treatment because of the intolerance

  during 3 days of treatment

• Failed for other reasons

  Number of failed for other reasons

  during 3 days of treatment

• Rate of participants with infection events

  Rate of participants with infection events (including skin infection, osteomyelitis of skull, or intracranial infection)

  within 90±7 days after randomization

• Rate of intracranial hemorrhage

  Rate of symptomatic and non-symptomatic intracranial hemorrhage

  within 90±7 days after randomization

• Rate of bleeding

  Rate of bleeding (moderate to severe bleeding, defined by the GUSTO)

  within 90±7 days after randomization

• Rate of hepatic insufficiency

  Rate of hepatic insufficiency: Posttreatment retest alanine aminotransferase(ALT) or aspartate transaminase(AST) value exceeds 3 times the upper normal limit

  within 90±7 days after randomization

• Rate of renal insufficiency

  Rate of renal insufficiency: glomerular filtration rate (GFR)\<40 ml/min/1.73m2 during the treatment

  within 90±7 days after randomization

• Anaemia

  Severe or extremely severe anaemia (hemoglobin \<60g / L)

  within 90±7 days after randomization

• Mortality

  Mortality

  within 90±7 days after randomization

• Adverse events / serious adverse events

  Incidence of other adverse events / serious adverse events reported

  within 90±7 days after randomization

Secondary Outcomes (12)

• Change of the NIHSS scores from baseline

  14±2 days after randomization or at discharge

• Patients with symptoms improvement

  baseline，7±2 days after randomization

• Patients with limbs' symptoms improvement

  baseline，at 7±2 days after randomization

• Change of core infarction volume from baseline

  baseline，7±2 days after randomization

• Change of GCS scores from baseline

  baseline, 14±2 days after randomization or at discharge

Study Arms (2)

Intracalvaria bone marrow injection group

EXPERIMENTAL

Y-3 ，Intracalvaria bone marrow injection , continuous medication for 3 days, with standard treatment and management according to the related guidelines.

Procedure: Intracalvaria bone marrow injection; Other: Conventional treatment

Conventional treatment group

SHAM COMPARATOR

standard treatment and management according to related guidelines

Other: Conventional treatment

Interventions

Intracalvaria bone marrow injection PROCEDURE

Intracalvaria bone marrow injection Y-3 (dose was given at 32 ug/kg), continuous medication for 3 days

Intracalvaria bone marrow injection group

Conventional treatment OTHER

standard treatment and management according to related guidelines

Conventional treatment group; Intracalvaria bone marrow injection group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old; 2.No gender limitation; 3.Pre-stroke mRS score \<2 4. Randomization can be finished within 24 hours of stroke onset (onset time is defined as last-seen-well time) 5. Ischemic stroke in the middle cerebral artery(MCA) territory meeting the following characteristics: A. 15\<NIHSS≤30 B. Imaging within 6h of onset indicated the core area of infarction (rCBF\<30% volume in CTP)\>1/2 MCA territory or ASPECTS score≤6 6.If endovascular-reperfusion therapy is performed, the treatment is not effective with one of the following conditions: A. The NIHSS score decreased≤4 and the total score was still\>15 B. The NIHSS score progressed immediately after the therapy and the total score≤30 7. Informed consent signed

You may not qualify if:

• Concurrent with one of the other cerebrovascular diseases of the following conditions:
• A.Acute cerebral hemorrhage or subarachnoid hemorrhage B. Acute posterior circulation infarction C.Other types of TOAST classification such as intracranial artery dissection, vasculitis and moyamoya disease
• Hemorrhagic transformation in the infarct area, over 30% of the infarct area, and significant occupancy effect
• Bilateral pupil fixation / pupillary reflex disappeared
• Decompressive craniectomy was planned before randomization
• Resistant hypertension (systolic\> 200mmHg or diastolic\> 110mmHg) or hypotension (systolic \<70mmHg or diastolic \<50mmHg)
• Abnormal blood glycemia before randomization (random venous blood glucose \<2.8 mmol/L or\> 23 mmol/L)
• Severe hepatic or renal insufficiency (Note: severe hepatic insufficiency refers to the ALT\> 3 times the upper limit of normal or the AST \> 3 times the upper limit of normal; severe renal insufficiency means the creatinine value\> 1.5 times the upper limit of normal or GFR \<40 ml/min/1.73m2)
• Severe cardiac insufficiency before randomization (compliance with New York College of Cardiology (NYHA) Cardiac Function Class III, IV)
• Dual antiplatelet (aspirin plus clopidogrel or ticagrelor or cilostazol) within 24 hours or tirofiban within 4 hours
• Combining with contraindications for intra-diplo administration, such as skull fracture, skull infection, subdural / external hematoma, subscalp hematoma, scalp skin or subcutaneous infection, etc
• Bleeding tendency (including but not limited to): platelet count \<100×109 / L; received heparin within nearly 24h, APTT ≥35s; oral warfarin, INR\>1.7; new-oral-anticoagulant orally; with direct thrombin or factor Xa inhibitor; Combining with coagulopathy such as hemophilia
• presence of severe or very severe anemia (hemoglobin \<60g / L)
• Combining with respiratory failure, and still difficult to correct after endotracheal intubation or tracheotomy, requiring ventilator treatment
• Combining with severe CNS degenerative disease, such as AD, PD and severe dementia from various causes

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (1)

Beijing Tiantan Hospital

Beijing, 100050, China

Location

Related Publications (20)

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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 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: PRINCIPAL INVESTIGATOR
• PI Title: Vice President of Beijing Tiantan Hospital

Study Record Dates

• First Submitted: April 6, 2023
• First Posted: May 9, 2023
• Study Start: April 17, 2023
• Primary Completion: November 6, 2023
• Study Completion: January 7, 2024
• Last Updated: April 26, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)