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

Primary Purpose

Stroke, Acute Ischemic

Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Intracalvaria bone marrow injection
Conventional treatment
Sponsored by
Beijing Tiantan Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stroke, Acute Ischemic focused on measuring malignant middle cerebral artery infarction, Y-3, postsynaptic density protein 95 inhibitor, BBB-bypassing route, brain drug delivery, Intracalvaria bone marrow injection

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 1.18-75 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 Exclusion Criteria: 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 Combining with other organic diseases, such as malignancy, the patient's life expectancy is less than 3 months Allergy to any component of the therapeutic drug Other neuroprotective agents without guideline recommendations and with unknown mechanism of the most important component were used within 24 hours of onset Patients with pregnancy, lactation, or a possible pregnancy and a planned pregnancy Unable to comply with the trial protocol or follow-up requirements Other circumstances deemed unsuitable by investigator Also participate in other interventional clinical trials

Sites / Locations

  • Beijing Tiantan HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Intracalvaria bone marrow injection group

Conventional treatment group

Arm Description

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

standard treatment and management according to related guidelines

Outcomes

Primary Outcome Measures

Failed of drilling
The rate of the internal plate of skull was drilled through
Number of drug-leakage events
Number of drug-leakage events
Patients' tolerance of therapy
The number of patient who refused to continue the treatment because of the intolerance
Failed for other reasons
Number of failed for other reasons
Rate of participants with infection events
Rate of participants with infection events (including skin infection, osteomyelitis of skull, or intracranial infection)
Rate of intracranial hemorrhage
Rate of symptomatic and non-symptomatic intracranial hemorrhage
Rate of bleeding
Rate of bleeding (moderate to severe bleeding, defined by the GUSTO)
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
Rate of renal insufficiency
Rate of renal insufficiency: glomerular filtration rate (GFR)<40 ml/min/1.73m2 during the treatment
Anaemia
Severe or extremely severe anaemia (hemoglobin <60g / L)
Mortality
Mortality
Adverse events / serious adverse events
Incidence of other adverse events / serious adverse events reported

Secondary Outcome Measures

Change of the NIHSS scores from baseline
Change of the NIHSS scores from baseline to 14±2 days or at discharge. The National Institutes of Health Stroke Scale (NIHSS) is a standardized neurological examination score that is a valid and reliable measure of disability and recovery after acute stroke. Scores range from 0 to 42, with higher scores indicating increasing severity.
Patients with symptoms improvement
The NIHSS scores improved by 4 points from baseline at 7±2 days
Patients with limbs' symptoms improvement
The NIHSS limb score improved by 2 points from baseline at 7±2 days
Change of core infarction volume from baseline
The core infarction volume is determined on CTP image with rCBF<30%
Change of GCS scores from baseline
The GCS is a validated and reliable scale to evaluate level of consciousness in patients. The scale assesses 3 functions: Eye Opening, Verbal Response, and Motor Response. GCS scores range from 15 (best) to 3 (worst).
90 days Functional improvement
The modified Rankin Scale 0-3 points at 90±7 days
Rate of decompressive hemicraniectomy according to guidelines
Rate of decompressive hemicraniectomy according to guidelines within 90±7 days
Rate of decompressive hemicraniectomy
Rate of decompressive hemicraniectomy
Days of NICU hospitalization
Days of NICU hospitalization
The cost of the NICU hospitalization
The cost of the NICU hospitalization
Patients with symptoms improvement
The NIHSS scores improved by 4 points from baseline at 14±2 days
Patients with limbs' symptoms improvement
The NIHSS limb score improved by 2 points from baseline at 14±2 days

Full Information

First Posted
April 6, 2023
Last Updated
October 18, 2023
Sponsor
Beijing Tiantan Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05849805
Brief Title
Y-3 Injection Through Skull Bone Marrow in the Treatment of Acute Malignant Middle Cerebral Artery Infarction (SOLUTION)
Official Title
The Feasibility, Safety and Efficacy of Y-3 Injection Through Skull Bone Marrow Bypassing Blood-brain Barrier in the Treatment of Acute Malignant Middle Cerebral Artery Infarction(SOLUTION)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 17, 2023 (Actual)
Primary Completion Date
October 31, 2023 (Anticipated)
Study Completion Date
February 13, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beijing Tiantan Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
The mortality rate of malignant middle cerebral artery infarction (mMCAI) is up to 80%, while current available treatment is limited. Mainstream therapeutics include endovascular reperfusion therapy and decompressive craniectomy. But endovascular-reperfusion has limits such as short time window and hemorrhagic transformation risk, while decompressive craniectomy can reduce mortality but not infarct volume. Curative effect of intravenous injection of neuroprotective drugs is severely limited because of the blood-brain barrier. Microchannels connecting the skull bone marrow and dura may be effective drug delivery shortcuts bypassing the blood-brain barrier. Cytoprotective drug Y-3 affects dual aspects of ischemic cascade by disrupting both function of the synaptic folding post-synaptic density protein 95 (PSD-95), as well as α2-γ⁃Aminobutyric acid type A receptor (α2-GABAAR) agonist. Preclinical testing proved that intracalvaria bone marrow injection of Y-3 solution 24h post rat permanent middle cerebral artery infarction reduced rat infarction volume and improved neurological function. 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. This is a prospective, randomized, open-label, blinded endpoint (PROBE) clinical trial. The trial planned to enroll 20 patients with mMCAI, aged 18-85 years, within 24 hours of onset, with contradictions of reperfusion therapy or poor reperfusion outcome. Patients will be randomly assigned to one of the following 2 groups at 1:1 ratio. Intracalvaria bone marrow injection group: intracalvaria bone marrow injection Y-3 (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. Conventional treatment group: standard treatment and management according to related guidelines Face to face interviews will be made on baseline, 4±1 days after randomization, 7±2 days after randomization, 14±2 days after randomization or discharge day, and 90 days after randomization. The primary outcomes include feasibility outcomes and safety outcomes. Feasibility Outcomes include the internal plate of skull was drilled throughly, drug leakage during injection, the patient refused to continue, failure for other reasons during 3 days'treatment. Safety Outcomes includes Infection events (skin infection, osteomyelitis, or intracranial infection), symptomatic and non-symptomatic intracranial hemorrhage, moderate to severe bleeding(defined by the GUSTO), hepatic insufficiency, renal insufficiency during the treatment, severe or extremely severe anaemia (hemoglobin <60g / L), mortality, incidence of other adverse events / serious adverse events reported. The secondary outcomes include change of the NIHSS scores from baseline to 14±2 days or at discharge, the NIHSS scores improved by 4 points from baseline at 7±2 days, the NIHSS limb score improved by 2 points from baseline at 7±2 days, change of core infarction volume from baseline to 7±2 days, change of Glasgow Coma Scale (GCS) scores from baseline values to 14±2 days or at discharge, the modified Rankin Scale(mRS) 0-3 points at 90±7 days, Rate of decompressive hemicraniectomy according to guidelines within 90±7 days, Rate of decompressive hemicraniectomy within 90±7 days, neurological intensive care unit (NICU) hospitalization days, cost of the NICU hospitalization Safety indicators will be compared using the Fisher exact probability method. Primary effectiveness measures will be tested by the t-test or the Wilcoxon rank-sum test. Secondary effectiveness measures will use the Fisher exact probability method, where the comparison of neurofunction scale or daily living energy scale will be performed using non-parametric analysis. NICU hospitalization days and NICU hospitalization costs differences will be compared using the t-test or Wilcoxon rank-sum test. All statistics will be two-sided, P <0.05 is considered statistically significant.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intracalvaria bone marrow injection group
Arm Type
Experimental
Arm Description
Y-3 ,Intracalvaria bone marrow injection , continuous medication for 3 days, with standard treatment and management according to the related guidelines.
Arm Title
Conventional treatment group
Arm Type
Sham Comparator
Arm Description
standard treatment and management according to related guidelines
Intervention Type
Procedure
Intervention Name(s)
Intracalvaria bone marrow injection
Intervention Description
Intracalvaria bone marrow injection Y-3 (dose was given at 32 ug/kg), continuous medication for 3 days
Intervention Type
Other
Intervention Name(s)
Conventional treatment
Intervention Description
standard treatment and management according to related guidelines
Primary Outcome Measure Information:
Title
Failed of drilling
Description
The rate of the internal plate of skull was drilled through
Time Frame
during 3 days of treatment
Title
Number of drug-leakage events
Description
Number of drug-leakage events
Time Frame
during 3 days of treatment
Title
Patients' tolerance of therapy
Description
The number of patient who refused to continue the treatment because of the intolerance
Time Frame
during 3 days of treatment
Title
Failed for other reasons
Description
Number of failed for other reasons
Time Frame
during 3 days of treatment
Title
Rate of participants with infection events
Description
Rate of participants with infection events (including skin infection, osteomyelitis of skull, or intracranial infection)
Time Frame
within 90±7 days after randomization
Title
Rate of intracranial hemorrhage
Description
Rate of symptomatic and non-symptomatic intracranial hemorrhage
Time Frame
within 90±7 days after randomization
Title
Rate of bleeding
Description
Rate of bleeding (moderate to severe bleeding, defined by the GUSTO)
Time Frame
within 90±7 days after randomization
Title
Rate of hepatic insufficiency
Description
Rate of hepatic insufficiency: Posttreatment retest alanine aminotransferase(ALT) or aspartate transaminase(AST) value exceeds 3 times the upper normal limit
Time Frame
within 90±7 days after randomization
Title
Rate of renal insufficiency
Description
Rate of renal insufficiency: glomerular filtration rate (GFR)<40 ml/min/1.73m2 during the treatment
Time Frame
within 90±7 days after randomization
Title
Anaemia
Description
Severe or extremely severe anaemia (hemoglobin <60g / L)
Time Frame
within 90±7 days after randomization
Title
Mortality
Description
Mortality
Time Frame
within 90±7 days after randomization
Title
Adverse events / serious adverse events
Description
Incidence of other adverse events / serious adverse events reported
Time Frame
within 90±7 days after randomization
Secondary Outcome Measure Information:
Title
Change of the NIHSS scores from baseline
Description
Change of the NIHSS scores from baseline to 14±2 days or at discharge. The National Institutes of Health Stroke Scale (NIHSS) is a standardized neurological examination score that is a valid and reliable measure of disability and recovery after acute stroke. Scores range from 0 to 42, with higher scores indicating increasing severity.
Time Frame
14±2 days after randomization or at discharge
Title
Patients with symptoms improvement
Description
The NIHSS scores improved by 4 points from baseline at 7±2 days
Time Frame
baseline,7±2 days after randomization
Title
Patients with limbs' symptoms improvement
Description
The NIHSS limb score improved by 2 points from baseline at 7±2 days
Time Frame
baseline,at 7±2 days after randomization
Title
Change of core infarction volume from baseline
Description
The core infarction volume is determined on CTP image with rCBF<30%
Time Frame
baseline,7±2 days after randomization
Title
Change of GCS scores from baseline
Description
The GCS is a validated and reliable scale to evaluate level of consciousness in patients. The scale assesses 3 functions: Eye Opening, Verbal Response, and Motor Response. GCS scores range from 15 (best) to 3 (worst).
Time Frame
baseline, 14±2 days after randomization or at discharge
Title
90 days Functional improvement
Description
The modified Rankin Scale 0-3 points at 90±7 days
Time Frame
90±7 days after randomization
Title
Rate of decompressive hemicraniectomy according to guidelines
Description
Rate of decompressive hemicraniectomy according to guidelines within 90±7 days
Time Frame
90±7 days after randomization
Title
Rate of decompressive hemicraniectomy
Description
Rate of decompressive hemicraniectomy
Time Frame
90±7 days after randomization
Title
Days of NICU hospitalization
Description
Days of NICU hospitalization
Time Frame
From date of randomization until the date of discharge or date of death from any cause, assessed up to 1 month
Title
The cost of the NICU hospitalization
Description
The cost of the NICU hospitalization
Time Frame
From date of randomization until the date of discharge or date of death from any cause, assessed up to 1 month
Title
Patients with symptoms improvement
Description
The NIHSS scores improved by 4 points from baseline at 14±2 days
Time Frame
baseline,14±2 days after randomization
Title
Patients with limbs' symptoms improvement
Description
The NIHSS limb score improved by 2 points from baseline at 14±2 days
Time Frame
baseline,at 14±2 days after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 1.18-75 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 Exclusion Criteria: 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 Combining with other organic diseases, such as malignancy, the patient's life expectancy is less than 3 months Allergy to any component of the therapeutic drug Other neuroprotective agents without guideline recommendations and with unknown mechanism of the most important component were used within 24 hours of onset Patients with pregnancy, lactation, or a possible pregnancy and a planned pregnancy Unable to comply with the trial protocol or follow-up requirements Other circumstances deemed unsuitable by investigator Also participate in other interventional clinical trials
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yilong Wang, PhD+MD
Phone
18842627325/13260180675
Email
yilong528@gmail.com
Facility Information:
Facility Name
Beijing Tiantan Hospital
City
Beijing
ZIP/Postal Code
100050
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yilong Wang, M.D.
Email
yilong538@gmail.com
First Name & Middle Initial & Last Name & Degree
yilong wang, M.D.

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
24481970
Citation
Wijdicks EF, Sheth KN, Carter BS, Greer DM, Kasner SE, Kimberly WT, Schwab S, Smith EE, Tamargo RJ, Wintermark M; American Heart Association Stroke Council. Recommendations for the management of cerebral and cerebellar infarction with swelling: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014 Apr;45(4):1222-38. doi: 10.1161/01.str.0000441965.15164.d6. Epub 2014 Jan 30.
Results Reference
background
PubMed Identifier
20354047
Citation
Treadwell SD, Thanvi B. Malignant middle cerebral artery (MCA) infarction: pathophysiology, diagnosis and management. Postgrad Med J. 2010 Apr;86(1014):235-42. doi: 10.1136/pgmj.2009.094292.
Results Reference
background
PubMed Identifier
33817340
Citation
Berge E, Whiteley W, Audebert H, De Marchis GM, Fonseca AC, Padiglioni C, de la Ossa NP, Strbian D, Tsivgoulis G, Turc G. European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke. Eur Stroke J. 2021 Mar;6(1):I-LXII. doi: 10.1177/2396987321989865. Epub 2021 Feb 19.
Results Reference
background
PubMed Identifier
34785611
Citation
Jadhav AP, Desai SM, Jovin TG. Indications for Mechanical Thrombectomy for Acute Ischemic Stroke: Current Guidelines and Beyond. Neurology. 2021 Nov 16;97(20 Suppl 2):S126-S136. doi: 10.1212/WNL.0000000000012801.
Results Reference
background
PubMed Identifier
30878104
Citation
Wu S, Wu B, Liu M, Chen Z, Wang W, Anderson CS, Sandercock P, Wang Y, Huang Y, Cui L, Pu C, Jia J, Zhang T, Liu X, Zhang S, Xie P, Fan D, Ji X, Wong KL, Wang L; China Stroke Study Collaboration. Stroke in China: advances and challenges in epidemiology, prevention, and management. Lancet Neurol. 2019 Apr;18(4):394-405. doi: 10.1016/S1474-4422(18)30500-3.
Results Reference
background
PubMed Identifier
31662037
Citation
Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2019 Dec;50(12):e344-e418. doi: 10.1161/STR.0000000000000211. Epub 2019 Oct 30. Erratum In: Stroke. 2019 Dec;50(12):e440-e441.
Results Reference
background
PubMed Identifier
17303527
Citation
Vahedi K, Hofmeijer J, Juettler E, Vicaut E, George B, Algra A, Amelink GJ, Schmiedeck P, Schwab S, Rothwell PM, Bousser MG, van der Worp HB, Hacke W; DECIMAL, DESTINY, and HAMLET investigators. Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials. Lancet Neurol. 2007 Mar;6(3):215-22. doi: 10.1016/S1474-4422(07)70036-4.
Results Reference
background
PubMed Identifier
23752906
Citation
Kolias AG, Kirkpatrick PJ, Hutchinson PJ. Decompressive craniectomy: past, present and future. Nat Rev Neurol. 2013 Jul;9(7):405-15. doi: 10.1038/nrneurol.2013.106. Epub 2013 Jun 11.
Results Reference
background
PubMed Identifier
27180033
Citation
Chamorro A, Dirnagl U, Urra X, Planas AM. Neuroprotection in acute stroke: targeting excitotoxicity, oxidative and nitrosative stress, and inflammation. Lancet Neurol. 2016 Jul;15(8):869-881. doi: 10.1016/S1474-4422(16)00114-9. Epub 2016 May 11.
Results Reference
background
PubMed Identifier
34830481
Citation
Ugalde-Trivino L, Diaz-Guerra M. PSD-95: An Effective Target for Stroke Therapy Using Neuroprotective Peptides. Int J Mol Sci. 2021 Nov 22;22(22):12585. doi: 10.3390/ijms222212585.
Results Reference
background
PubMed Identifier
21102461
Citation
Zhou L, Li F, Xu HB, Luo CX, Wu HY, Zhu MM, Lu W, Ji X, Zhou QG, Zhu DY. Treatment of cerebral ischemia by disrupting ischemia-induced interaction of nNOS with PSD-95. Nat Med. 2010 Dec;16(12):1439-43. doi: 10.1038/nm.2245. Epub 2010 Nov 21. Erratum In: Nat Med. 2011 Sep;17(9):1153.
Results Reference
background
PubMed Identifier
32087818
Citation
Hill MD, Goyal M, Menon BK, Nogueira RG, McTaggart RA, Demchuk AM, Poppe AY, Buck BH, Field TS, Dowlatshahi D, van Adel BA, Swartz RH, Shah RA, Sauvageau E, Zerna C, Ospel JM, Joshi M, Almekhlafi MA, Ryckborst KJ, Lowerison MW, Heard K, Garman D, Haussen D, Cutting SM, Coutts SB, Roy D, Rempel JL, Rohr AC, Iancu D, Sahlas DJ, Yu AYX, Devlin TG, Hanel RA, Puetz V, Silver FL, Campbell BCV, Chapot R, Teitelbaum J, Mandzia JL, Kleinig TJ, Turkel-Parrella D, Heck D, Kelly ME, Bharatha A, Bang OY, Jadhav A, Gupta R, Frei DF, Tarpley JW, McDougall CG, Holmin S, Rha JH, Puri AS, Camden MC, Thomalla G, Choe H, Phillips SJ, Schindler JL, Thornton J, Nagel S, Heo JH, Sohn SI, Psychogios MN, Budzik RF, Starkman S, Martin CO, Burns PA, Murphy S, Lopez GA, English J, Tymianski M; ESCAPE-NA1 Investigators. Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial. Lancet. 2020 Mar 14;395(10227):878-887. doi: 10.1016/S0140-6736(20)30258-0. Epub 2020 Feb 20.
Results Reference
background
PubMed Identifier
25561720
Citation
Daneman R, Prat A. The blood-brain barrier. Cold Spring Harb Perspect Biol. 2015 Jan 5;7(1):a020412. doi: 10.1101/cshperspect.a020412.
Results Reference
background
PubMed Identifier
33649582
Citation
Terstappen GC, Meyer AH, Bell RD, Zhang W. Strategies for delivering therapeutics across the blood-brain barrier. Nat Rev Drug Discov. 2021 May;20(5):362-383. doi: 10.1038/s41573-021-00139-y. Epub 2021 Mar 1.
Results Reference
background
PubMed Identifier
31839374
Citation
Charabati M, Rabanel JM, Ramassamy C, Prat A. Overcoming the Brain Barriers: From Immune Cells to Nanoparticles. Trends Pharmacol Sci. 2020 Jan;41(1):42-54. doi: 10.1016/j.tips.2019.11.001. Epub 2019 Dec 12.
Results Reference
background
PubMed Identifier
31546096
Citation
Xie J, Shen Z, Anraku Y, Kataoka K, Chen X. Nanomaterial-based blood-brain-barrier (BBB) crossing strategies. Biomaterials. 2019 Dec;224:119491. doi: 10.1016/j.biomaterials.2019.119491. Epub 2019 Sep 14.
Results Reference
background
PubMed Identifier
30150661
Citation
Herisson F, Frodermann V, Courties G, Rohde D, Sun Y, Vandoorne K, Wojtkiewicz GR, Masson GS, Vinegoni C, Kim J, Kim DE, Weissleder R, Swirski FK, Moskowitz MA, Nahrendorf M. Direct vascular channels connect skull bone marrow and the brain surface enabling myeloid cell migration. Nat Neurosci. 2018 Sep;21(9):1209-1217. doi: 10.1038/s41593-018-0213-2. Epub 2018 Aug 27.
Results Reference
background
PubMed Identifier
34083450
Citation
Brioschi S, Wang WL, Peng V, Wang M, Shchukina I, Greenberg ZJ, Bando JK, Jaeger N, Czepielewski RS, Swain A, Mogilenko DA, Beatty WL, Bayguinov P, Fitzpatrick JAJ, Schuettpelz LG, Fronick CC, Smirnov I, Kipnis J, Shapiro VS, Wu GF, Gilfillan S, Cella M, Artyomov MN, Kleinstein SH, Colonna M. Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders. Science. 2021 Jul 23;373(6553):eabf9277. doi: 10.1126/science.abf9277. Epub 2021 Jun 3.
Results Reference
background
PubMed Identifier
35501382
Citation
Pulous FE, Cruz-Hernandez JC, Yang C, Kaya Zeta, Paccalet A, Wojtkiewicz G, Capen D, Brown D, Wu JW, Schloss MJ, Vinegoni C, Richter D, Yamazoe M, Hulsmans M, Momin N, Grune J, Rohde D, McAlpine CS, Panizzi P, Weissleder R, Kim DE, Swirski FK, Lin CP, Moskowitz MA, Nahrendorf M. Cerebrospinal fluid can exit into the skull bone marrow and instruct cranial hematopoiesis in mice with bacterial meningitis. Nat Neurosci. 2022 May;25(5):567-576. doi: 10.1038/s41593-022-01060-2. Epub 2022 May 2.
Results Reference
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PubMed Identifier
35301477
Citation
Mazzitelli JA, Smyth LCD, Cross KA, Dykstra T, Sun J, Du S, Mamuladze T, Smirnov I, Rustenhoven J, Kipnis J. Cerebrospinal fluid regulates skull bone marrow niches via direct access through dural channels. Nat Neurosci. 2022 May;25(5):555-560. doi: 10.1038/s41593-022-01029-1. Epub 2022 Mar 17.
Results Reference
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Y-3 Injection Through Skull Bone Marrow in the Treatment of Acute Malignant Middle Cerebral Artery Infarction (SOLUTION)

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