An interventional study of RK-4 ICO injection and Conventional treatment in Stroke, Acute Ischemic Stroke and Blood-Brain Barrier, sponsored by yilong Wang. Not yet recruiting at 1 site in China. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-04-07.
Sponsored by yilong Wang · Not applicable, Interventional, and Treatment
A pilot study confirmed the feasibility and safety of neuroprotectant RK-4 intracalvariosseous(ICO) injection in patients with malignant middle cerebral artery infarction (mMCAI), showing a trend in improving 90-day functional scores compared to conventional treatment. The aim of this trial is to investigate the feasibility and safety of neuroprotective agent RK-4 injection using intracalvariosseous injection device in patients with acute large hemispheric infarction (LHI) who has contraindications of reperfusion therapy or have got poor reperfusion therapy outcomes.
The mortality rate of large hemispheric infarction (LHI) is up to 40%-60%, 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 RK-4 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-v#Aminobutyric acid type A receptor (α2-GABAAR) agonist. Phase I and Phase II clinical trials have confirmed the safety and efficacy of intravenous infusion of RK-4 in treating cerebral infarction, with the optimal dosage being 40mg. Preclinical testing proved that ICO injection of RK-4 solution 24h post rat permanent middle cerebral artery infarction reduced rat infarction volume and improved neurological function. Previously, our team has conducted the RK-4 intracalvariosseous administration in the earlier SOLUTION clinical trail through the existing neurosurgical devices. Although the safety and efficacy were preliminarily demonstrated, present administration device is not minimally invasive and requires operation in the ICU, which leads to a higher risk of the inner plate penetration. The new intracalvariosseous injection device shows promising prospective in precise control of the drilling speed and depth, and better achievement of accurate, high-efficiency and microinvasive drug delivery.
The study is a single-centered, prospective, randomized, open-label study. The purpose of this study is to investigate the feasibility and safety of RK-4 injection using intracalvariosseous injection device in acute LHI patients with contraindications of reperfusion therapy or poor outcomes.
Patients will be randomly assigned to one of the following 2 groups at 1:1 ratio.
ICO injection group: RK-4 ICO injection through intracalvariosseous injection device (using an electric bone drill to drill 3 holes (each for 1-time administration) from the outer plate of the skull without penetrating the inner cranial plate), 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: Conventional treatment group will receive standard treatment and management according to related guidelines.
Face to face interviews will be made on baseline, 4±1 days after randomization, 8±1 days after randomization, 14±1 days after randomization or discharge day, and 90±7 days,180±14 days after randomization.
The primary outcomes include feasibility outcomes and safety outcomes. Feasibility Outcomes include the internal plate of skull was drilled thoroughly, 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, severe 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 the effectiveness outcomes. The effectiveness outcomes include change of Glasgow Coma Scale (GCS) scores from baseline values to 14±1 days or at discharge, the change of the The National Institutes of Health Stroke Scale (NIHSS) scores from baseline to 14±1 days or at discharge, the modified Rankin Scale(mRS) 0-3 points at 90±7 days and the mRS 0-3 points at 180±14 days.
A Data and Safety Monitoring Board (DSMB) will regularly monitor safety during the study. The trial has been approved by Institutional Review Board (IRB) and Ethics Committee (EC) in Being Tiantan hospital, Capital Medical University.
2,612 studies on the registry are indexed under Ischemic Stroke; 971 are open to participants now.
This study's planned enrollment of 6 is below the median of 120 across 1,776 interventional studies indexed under Ischemic Stroke.
Browse Ischemic Stroke studies →yilong Wang is the lead sponsor of 7 studies on the registry; 7 are open to participants now.
Compared within Ischemic Stroke, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Stroke. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Clinical symptoms, signs and imaging diagnosis of cerebral infarction in the area supplied by the middle cerebral artery, together with the following features:
Exclusion Criteria:
Complications with other cerebrovascular diseases meet one of the following conditions:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
COPD
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RK-4 ICO injection through intracalvariosseous injection device (drilling 3 holes (each for 1-time administration) from the outer cranial plate without penetrating the inner plate), 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.
Device: RK-4 ICO injection · Other: Conventional treatment
standard treatment and management according to related guidelines.
Other: Conventional treatment
Patients included will be given skull outer plate drilling surgery and RK-4 ICO injection under local anesthesia and sedation using the intracalvariosseous injection device. The drilling and injection will be conducted once a day for 3 consecutive days.
standard treatment and management according to related guidelines
Failed of drilling
The rate of the internal plate of skull was drilled through
Time frame: during 3 days of treatment
Number of drug-leakage events
Number of drug-leakage events
Time frame: during 3 days of treatment
Patients' tolerance of therapy
The number of patients who refused to continue the treatment because of the intolerance
Time frame: during 3 days of treatment
Failed for other reasons
Number of failed for other reasons
Time frame: 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)
Time frame: within 90±7 days after randomization
Rate of intracranial hemorrhage
Rate of symptomatic and non-symptomatic intracranial hemorrhage
Time frame: within 90±7 days after randomization
Rate of bleeding
Rate of bleeding (moderate to severe bleeding, defined by the GUSTO)
Time frame: within 90±7 days after randomization
Rate of hepatic insufficiency
Rate of hepatic insufficiency: serum alanine aminotransferase (ALT), or aspartate aminotransferase (AST) \> 5 times the upper limit of normal (ULN), or alkaline phosphatase (APL)\> 2 times the ULN or the multiple of the abnormal baseline value before medication; Or, serum total bilirubin (TBil) \> 2.5 mg/dL (42.75 μmol/L), accompanied by increased levels of serum AST, ALT or ALP.
Time frame: within 90±7 days after randomization
Rate of severe renal insufficiency
Rate of severe renal insufficiency: estimated glomerular filtration rate (eGFR)\<30 ml/min/1.73m2 during the treatment.
Time frame: within 90±7 days after randomization
Severe or extremely severe anaemia
Severe or extremely severe anaemia (hemoglobin \<60g / L)
Time frame: within 90±7 days after randomization
Mortality
Mortality
Time frame: within 90±7 days after randomization
Adverse events / serious adverse events
Incidence of other adverse events / serious adverse events reported.
Time frame: within 90±7 days after randomization
Change of GCS scores from baseline
The Glasgow Coma Scale (GCS) score 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±1 days after randomization or at discharge
Change of the NIHSS scores from baseline
Change of the National Institutes of Health Stroke Scale (NIHSS) scores from baseline to 14±1days or at discharge. The 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±1 days after randomization or at discharge
90 days functional improvement
The modified Rankin Scale 0-3 points at 90±7 days. Functional improvement is defined as a dichotomized modified Rankin Scale(mRS) 0-3 outcome. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale runs from 0-6 with "0" being perfect health without symptoms to "6" being death. Score 0: No symptoms Score 1: No significant disability. Able to carry out all usual activities, despite some symptoms. Score 2: Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. Score 3: Moderate disability. Requires some help, but able to walk unassisted. Score 4: Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. Score 5: Severe disability. Requires constant nursing care and attention, bedridden, incontinent. Score 6: Dead
Time frame: 90±7 days after randomization
180 days functional improvement
The modified Rankin Scale 0-3 points at 180±14 days. Functional improvement is defined as a dichotomized modified Rankin Scale(mRS) 0-3 outcome. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale runs from 0-6 with "0" being perfect health without symptoms to "6" being death. Score 0: No symptoms Score 1: No significant disability. Able to carry out all usual activities, despite some symptoms. Score 2: Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. Score 3: Moderate disability. Requires some help, but able to walk unassisted. Score 4: Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. Score 5: Severe disability. Requires constant nursing care and attention, bedridden, incontinent. Score 6: Dead
Time frame: 180±14 days after randomization
Plan to share: No
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