Stroke, Acute IschemicNCT05849805
Y-3 Injection Through Skull Bone Marrow in the Treatment of Acute Malignant Middle Cerebral Artery Infarction (SOLUTION)
A study testing Intracalvaria bone marrow injection and Conventional treatment in people with Stroke, Acute Ischemic, run by Beijing Tiantan Hospital at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Stroke, Acute Ischemic
- What is being tested?
- Intracalvaria bone marrow injection and Conventional treatment
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 17 Apr 2023to 7 Jan 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 22Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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)
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.
Read the 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.
- Conditions
- Stroke, Acute Ischemic
- Being tested
- Intracalvaria bone marrow injection, Conventional treatment
- Keywords
- malignant middle cerebral artery infarction, Y-3, postsynaptic density protein 95 inhibitor, BBB-bypassing route, brain drug delivery, Intracalvaria bone marrow injection
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intracalvaria bone marrow injectionProcedure or surgery
Intracalvaria bone marrow injection Y-3 (dose was given at 32 ug/kg), continuous medication for 3 days
Conventional treatmentOther
standard treatment and management according to related guidelines
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Intracalvaria bone marrow injection; Other: Conventional treatment |
| Conventional treatment group | Sham comparator | standard treatment and management according to related guidelines Receives: Other: Conventional treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Failed of drilling
The rate of the internal plate of skull was drilled through
Measured: during 3 days of treatment
Number of drug-leakage events
Number of drug-leakage events
Measured: during 3 days of treatment
Patients' tolerance of therapy
The number of patient who refused to continue the treatment because of the intolerance
Measured: during 3 days of treatment
Failed for other reasons
Number of failed for other reasons
Measured: 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)
Measured: within 90±7 days after randomization
Rate of intracranial hemorrhage
Rate of symptomatic and non-symptomatic intracranial hemorrhage
Measured: within 90±7 days after randomization
Rate of bleeding
Rate of bleeding (moderate to severe bleeding, defined by the GUSTO)
Measured: 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
Measured: 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
Measured: within 90±7 days after randomization
Anaemia
Severe or extremely severe anaemia (hemoglobin <60g / L)
Measured: within 90±7 days after randomization
Mortality
Mortality
Measured: within 90±7 days after randomization
Adverse events / serious adverse events
Incidence of other adverse events / serious adverse events reported
Measured: within 90±7 days after randomization
Secondary outcomes (12)
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.
Measured: 14±2 days after randomization or at discharge
Patients with symptoms improvement
The NIHSS scores improved by 4 points from baseline at 7±2 days
Measured: baseline，7±2 days after randomization
Patients with limbs' symptoms improvement
The NIHSS limb score improved by 2 points from baseline at 7±2 days
Measured: baseline，at 7±2 days after randomization
Change of core infarction volume from baseline
The core infarction volume is determined on CTP image with rCBF<30%
Measured: baseline，7±2 days after randomization
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).
Measured: baseline, 14±2 days after randomization or at discharge
90 days Functional improvement
The modified Rankin Scale 0-3 points at 90±7 days
Measured: 90±7 days after randomization
Rate of decompressive hemicraniectomy according to guidelines
Rate of decompressive hemicraniectomy according to guidelines within 90±7 days
Measured: 90±7 days after randomization
Rate of decompressive hemicraniectomy
Rate of decompressive hemicraniectomy
Measured: 90±7 days after randomization
Days of NICU hospitalization
Days of NICU hospitalization
Measured: From date of randomization until the date of discharge or date of death from any cause, assessed up to 1 month
The cost of the NICU hospitalization
The cost of the NICU hospitalization
Measured: From date of randomization until the date of discharge or date of death from any cause, assessed up to 1 month
Patients with symptoms improvement
The NIHSS scores improved by 4 points from baseline at 14±2 days
Measured: baseline，14±2 days after randomization
Patients with limbs' symptoms improvement
The NIHSS limb score improved by 2 points from baseline at 14±2 days
Measured: baseline，at 14±2 days after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2023
- Study start17 Apr 2023
- Primary completion6 Nov 2023
- Study completion7 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for Stroke, Acute IschemicStudies of the same condition, open and under way.
- More trials run by Beijing Tiantan HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beijing Tiantan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, yilong Wang, Beijing Tiantan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05849805
- Sponsor's protocol ID
- KY2023-052-02
- Status last verified
- Apr 2024
- First submitted
- 6 Apr 2023
- Last updated
- 26 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 24481970Treadwell 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.
PubMed 20354047Berge 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.
PubMed 33817340Jadhav 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.
PubMed 34785611Wu 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.
PubMed 30878104Powers 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.
PubMed 31662037Vahedi 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.
PubMed 17303527Kolias 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.
PubMed 23752906Chamorro 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.
PubMed 27180033Ugalde-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.
PubMed 34830481Zhou 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.
PubMed 21102461Hill 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.
PubMed 32087818Daneman R, Prat A. The blood-brain barrier. Cold Spring Harb Perspect Biol. 2015 Jan 5;7(1):a020412. doi: 10.1101/cshperspect.a020412.
PubMed 25561720Terstappen 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.
PubMed 33649582Charabati 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.
PubMed 31839374
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05849805
- Acronym / sponsor ID
- KY2023-052-02
- 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
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Beijing Tiantan HospitalUniversity, hospital or other
- Study start
- 17 Apr 2023 (actual)
- Primary completion
- 6 Nov 2023 (actual)
- Study completion
- 7 Jan 2024 (actual)
- First posted
- 9 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intracalvaria bone marrow injection group | Experimental | Procedure: Intracalvaria bone marrow injection, Other: Conventional treatmentY-3 ，Intracalvaria bone marrow injection , continuous medication for 3 days, with standard treatment and management according to the related guidelines. |
| Conventional treatment group | Sham comparator | Other: Conventional treatmentstandard treatment and management according to related guidelines |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intracalvaria bone marrow injectionIntracalvaria bone marrow injection Y-3 (dose was given at 32 ug/kg), continuous medication for 3 days | Procedure or surgery | Intracalvaria bone marrow injection group |
| Conventional treatmentstandard treatment and management according to related guidelines | Other | Conventional treatment group, Intracalvaria bone marrow injection group |
Primary outcome
Failed of drilling
Time frame: during 3 days of treatment
The rate of the internal plate of skull was drilled through
Number of drug-leakage events
Time frame: during 3 days of treatment
Number of drug-leakage events
Patients' tolerance of therapy
Time frame: during 3 days of treatment
The number of patient who refused to continue the treatment because of the intolerance
Failed for other reasons
Time frame: during 3 days of treatment
Number of failed for other reasons
Rate of participants with infection events
Time frame: within 90±7 days after randomization
Rate of participants with infection events (including skin infection, osteomyelitis of skull, or intracranial infection)
Rate of intracranial hemorrhage
Time frame: within 90±7 days after randomization
Rate of symptomatic and non-symptomatic intracranial hemorrhage
Rate of bleeding
Time frame: within 90±7 days after randomization
Rate of bleeding (moderate to severe bleeding, defined by the GUSTO)
Rate of hepatic insufficiency
Time frame: within 90±7 days after randomization
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
Time frame: within 90±7 days after randomization
Rate of renal insufficiency: glomerular filtration rate (GFR)<40 ml/min/1.73m2 during the treatment
Anaemia
Time frame: within 90±7 days after randomization
Severe or extremely severe anaemia (hemoglobin <60g / L)
Mortality
Time frame: within 90±7 days after randomization
Mortality
Adverse events / serious adverse events
Time frame: within 90±7 days after randomization
Incidence of other adverse events / serious adverse events reported
12 secondary outcomes
Change of the NIHSS scores from baseline
Time frame: 14±2 days after randomization or at discharge
Patients with symptoms improvement
Time frame: baseline，7±2 days after randomization
Patients with limbs' symptoms improvement
Time frame: baseline，at 7±2 days after randomization
Change of core infarction volume from baseline
Time frame: baseline，7±2 days after randomization
Change of GCS scores from baseline
Time frame: baseline, 14±2 days after randomization or at discharge
90 days Functional improvement
Time frame: 90±7 days after randomization
Rate of decompressive hemicraniectomy according to guidelines
Time frame: 90±7 days after randomization
Rate of decompressive hemicraniectomy
Time frame: 90±7 days after randomization
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
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
Patients with symptoms improvement
Time frame: baseline，14±2 days after randomization
Patients with limbs' symptoms improvement
Time frame: baseline，at 14±2 days after randomization
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2024.
- Background: PubMed 24481970Wijdicks 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.
- Background: PubMed 20354047Treadwell 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.
- Background: PubMed 33817340Berge 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.
- Background: PubMed 34785611Jadhav 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.
- Background: PubMed 30878104Wu 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.
- Background: PubMed 31662037Powers 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.
- Background: PubMed 17303527Vahedi 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.
- Background: PubMed 23752906Kolias 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.
- Background: PubMed 27180033Chamorro 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.
- Background: PubMed 34830481Ugalde-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.
- Background: PubMed 21102461Zhou 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.
- Background: PubMed 32087818Hill 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intracalvaria bone marrow injection and Conventional treatment in people with Stroke, Acute Ischemic, run by Beijing Tiantan Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Failed of drilling (time frame: during 3 days of treatment). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05849805, which also lists 20 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2024.