An interventional study of Intracalvariosseous injection vancomycin/tigecycline/polymyxin B and Intravenous injection vancomycin/tigecycline/polymyxin B in Blood-Brain Barrier and Bacterial Meningitis, sponsored by yilong Wang. Not yet recruiting at 1 site in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-09-17.
Sponsored by yilong Wang · Not applicable, Interventional, and Treatment
Multiple preclinical and clinical studies, including the investigators' published work and the ongoing SOLUTION series trials, have consistently demonstrated that intracalvariosseous (ICO) injection can markedly increase drug exposure in the central nervous system with an acceptable safety profile. This is a multicenter, prospective, single-arm, open-label, exploratory clinical study designed to evaluate the feasibility, safety and preliminary efficacy of antibiotic delivery via the ICO route combined with standard intravenous therapy in patients with moderate-to-severe bacterial meningitis who have shown an inadequate response to standard antibiotic treatment.
Bacterial meningitis remains a major cause of death and long-term neurological disability despite advances in antimicrobial therapy, vaccination and critical care. Moderate-to-severe disease, particularly healthcare-associated ventriculitis/meningitis and infections caused by multidrug-resistant (MDR) pathogens, continues to pose substantial therapeutic challenges. Intravenous antibiotic therapy alone often fails to achieve sufficiently rapid and sustained therapeutic drug concentrations in cerebrospinal fluid (CSF) and at the meningeal surface due to the blood-brain barrier. Although intrathecal and intraventricular administration can increase local drug concentrations, these approaches carry high complication risks and have limited diffusion in the subarachnoid space.
Anatomical and physiological studies have demonstrated direct communication pathways between calvarial bone marrow, dura mater, CSF spaces and the glymphatic system, providing a biological rationale for intracalvariosseous (ICO) injection as a regional drug delivery route to the central nervous system. Preclinical and clinical evidence, including the investigators' published work and the ongoing SOLUTION series clinical trials, confirms that ICO delivery can enhance local CNS drug exposure without disrupting the blood-brain barrier, with a manageable safety profile. In addition, the investigators' exploratory animal study of vancomycin delivered via ICO in a bacterial meningitis model further demonstrated improved anti-infective efficacy at reduced systemic doses.
This trial is a multicenter, prospective, single-arm, open-label, exploratory clinical study. A total of 9 eligible patients will be enrolled across 3+ medical centers led by Beijing Tiantan Hospital, Capital Medical University.
Eligible participants are adults aged 18-75 years with moderate-to-severe bacterial meningitis who show no improvement or clinical deterioration after a course of empiric or targeted intravenous antibiotic therapy, and for whom treatment with polymyxin B, tigecycline or vancomycin is clinically indicated.
All enrolled participants will receive guideline-concordant standard supportive care (including intracranial pressure management, seizure control, organ support and symptomatic treatment) plus optimized intravenous antibiotic therapy. In addition, all participants will undergo bilateral parietal burr hole placement of cranial bolt delivery devices, followed by continuous infusion of the selected antibiotic via the calvarial bone marrow route for 7 consecutive days (7×24 hours). The ICO delivery device will be removed after the 7-day infusion course, and the duration of subsequent intravenous antibiotic therapy will be adjusted according to clinical and laboratory response. Rescue intrathecal or intraventricular antibiotic therapy will be initiated if predefined criteria of no improvement are met within the first 3 days of combined treatment.
Study visits are scheduled at:
Baseline (screening and enrollment) Day 1 (ICO device placement and treatment initiation) Days 2-4 (early efficacy assessment) Day 8 Day 15 Month 1 (±3 days) Month 3 (±7 days, telephone follow-up) A Data and Safety Monitoring Board (DSMB) will regularly monitor safety and study conduct throughout the trial. The study has been approved by the Institutional Review Board / Ethics Committee of Beijing Tiantan Hospital, Capital Medical University.
38 studies on the registry are indexed under Meningitis, Bacterial; 11 are open to participants now.
This study's planned enrollment of 9 is below the median of 226 across 22 interventional studies indexed under Meningitis, Bacterial.
Browse Meningitis, Bacterial studies →yilong Wang is the lead sponsor of 7 studies on the registry; 7 are open to participants now.
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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.
Meeting the diagnostic criteria for bacterial meningitis (at least item i must be satisfied):
i. Clinical diagnosis: abnormal body temperature (>38 ℃ or \<36 ℃), turbid or purulent cerebrospinal fluid (CSF), CSF leukocytosis (>500 × 10⁶/L), CSF glucose/serum glucose ratio \< 0.4, CSF protein concentration > 50 mg/dL; ii. Etiological diagnosis: on the basis of item i, positive microbial detection or culture from specimen smears, drainage catheter tips, implants or CSF (excluding contamination and colonization).
Glasgow Coma Scale (GCS) score ≤ 12, or a decrease of ≥ 2 points from the previous assessment; At least one of the following: altered consciousness, seizures, brain parenchymal involvement, mechanical ventilation, or circulatory support.
Exclusion Criteria:
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.
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.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
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.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
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.
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.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
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.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
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.
In patients who fail to respond to the initial intravenous antibiotic regimen, intravenous treatment will be switched to the indicated antibiotic (polymyxin B, tigecycline, or vancomycin). At the same time, bilateral parietal outer-table drill holes will be created, delivery devices will be secured, and the corresponding antibiotic (polymyxin B, tigecycline, or vancomycin) will be continuously infused via the intracalvariosseous route. The combined ICO and intravenous treatment will be administered concurrently for 7 × 24 hours, after which the ICO devices will be removed. The duration of intravenous therapy will then be adjusted according to treatment response, including clinical symptoms, signs, and laboratory findings.
Procedure: Intracalvariosseous injection vancomycin/tigecycline/polymyxin B · Drug: Intravenous injection vancomycin/tigecycline/polymyxin B · Other: Conventional treatment
Continuous intracalvariosseous infusion of polymyxin B (12.5 mg/day), tigecycline (12.5 mg/day), and vancomycin (125 mg/day).
Intravenous infusion of polymyxin B (100 mg/day), tigecycline (100 mg/day), and vancomycin (2000 mg/day).
Standard treatment and management according to related guidelines during the entire treatment period
Feasibility and safety of cranial burr hole procedure and 7-day continuous intracalvariosseous antibiotic infusion
Success rate of parietal burr hole placement; proportion of participants who complete 7×24-hour continuous antibiotic infusion via the intracalvariosseous route; incidence of device dislodgement, leakage, occlusion and unplanned infusion interruption.
Time frame: From Day 1 (device placement) to Day 8 (device removal)
Proportion of participants requiring rescue intrathecal/intraventricular antibiotic therapy within 3 days after intervention initiation
The proportion of participants who meet predefined inadequate response criteria within the first 3 days (such as Day 2, 3, 4) of combined therapy and thus receive rescue intrathecal (IT) or intraventricular (IVT) antibiotics. Inadequate response is defined as ≥2 of the following 4 items showing no improving trend or deterioration compared with baseline in at least 2 consecutive clinical evaluations: Intracranial infection-related clinical signs and symptoms Cerebrospinal fluid (CSF) white blood cell count CSF protein concentration CSF/serum glucose concentration ratio
Time frame: Within 3 days after initiation of intracalvariosseous treatment, such as Day 2, 3, 4.
Overall clinical response rate at Day 8 and Day 15
Overall response rate = \[(Cure + Improvement) / Total number of evaluable participants\] × 100% Cure: CSF white blood cell count, CSF protein concentration, CSF/serum glucose ratio, and CSF bacterial culture are all normal in 2 consecutive tests. Improvement: All 4 above CSF indicators are normal in at least 1 test. Ineffective: All 4 above CSF indicators remain abnormal in 2 consecutive tests. Normal reference values for CSF indicators: White blood cell count: \< 100 × 10⁶/L Protein concentration: \< 50 mg/dL CSF/serum glucose ratio: \> 0.5
Time frame: Day 8, Day 15 after intervention initiation
Cure rate at Day 8 and Day 15
Definition: Proportion of participants meeting the "Cure" criteria defined above.
Time frame: Day 8, Day 15 after intervention initiation
Improvement rate at Day 8 and Day 15
Definition: Proportion of participants meeting the "Improvement" criteria defined above.
Time frame: Day 8, Day 15 after intervention initiation
Cerebrospinal fluid white blood cell count at Days 2-4 and Day 8, Day 15 after intervention initiation
Cerebrospinal fluid white blood cell count
Time frame: Days 2-4 and Day 8, Day 15 after intervention initiation
Cerebrospinal fluid protein concentration at Days 2-4 and Day 8, Day 15 after intervention initiation
Cerebrospinal fluid protein concentration
Time frame: Days 2-4 and Day 8, Day 15 after intervention initiation
Cerebrospinal fluid-to-serum glucose concentration ratio at Days 2-4 and Day 8, Day 15 after intervention initiation
Cerebrospinal fluid-to-serum glucose concentration ratio
Time frame: Days 2-4 and Day 8, Day 15 after intervention initiation
CSF bacterial culture results and pathogen clearance status
Cerebrospinal fluid bacteriological culture results
Time frame: Days 2-4 and Day 8, Day 15 after intervention initiation
Glasgow Coma Scale (GCS) score and its change from baseline
GCS assesses consciousness level via 3 components (eye opening, verbal response, motor response). Total score ranges 3-15; higher scores indicate better neurological status.
Time frame: Days 2-4 and Day 8, Day 15 after intervention initiation
All-cause mortality within 14 days of intervention initiation
All-cause mortality is equal to the ratio of the number of all-cause deaths to the total number of cases within the same treatment group
Time frame: Within 14 days of the start of the intervention
Mortality due to meningitis within 14 days of intervention initiation
Mortality due to meningitis. The diagnostic criteria are the absence of a downward trend in the cerebrospinal fluid leukocyte count, protein concentration, and the ratio of cerebrospinal fluid glucose concentration to serum glucose concentration prior to death.
Time frame: Within 14 days of the start of the intervention
Antibiotic concentrations in CSF and plasma, and CSF/plasma concentration ratio
The ratio of cerebrospinal fluid drug concentration to plasma drug concentration
Time frame: 0.25, 0.5, 1, 2, 4, 8, 12, 24 hours and Days 2-4, Day 8 after intervention initiation.
Bacterial culture results of calvarial bone marrow fluid before and after intracalvariosseous treatment
calvarial bone marrow fluid bacteriological culture results
Time frame: Day 1 (device placement) and Day 8 (device removal)
Glasgow Outcome Scale (GOS) score at 1 month (±3 days), 3 months (±7 days) after intervention initiation
5-point functional scale: 1 = death, 2 = vegetative state, 3 = severe disability, 4 = moderate disability, 5 = good recovery. Higher scores indicate better functional outcome
Time frame: 1 month (±3 days), 3 months (±7 days) after intervention initiation
Cure rate without neurological sequelae at 1 month (±3 days), 3 months (±7 days) after intervention initiation
Proportion of participants with normalized CSF indicators and no new meningitis-attributable neurological deficits.
Time frame: 1 month (±3 days), 3 months (±7 days) after intervention initiation
All-cause mortality at 1 month (±3 days), 3 months (±7 days) after intervention initiation
All-cause mortality is equal to the ratio of the number of all-cause deaths to the total number of cases within the same treatment group
Time frame: 1 month (±3 days), 3 months (±7 days) after intervention initiation
Meningitis-related mortality at 1 month (±3 days), 3 months (±7 days) after intervention initiation
Meningitis-related mortality is equal to the ratio of the number of deaths due to meningitis to the total number of cases within the same treatment group. Meningitis-related mortality. The diagnostic criteria are the absence of a downward trend in the cerebrospinal fluid leukocyte count, protein concentration, and the ratio of cerebrospinal fluid glucose concentration to serum glucose concentration prior to death.
Time frame: 1 month (±3 days), 3 months (±7 days) after intervention initiation
Reinfection with the same microorganism occurred at 1 month (±3 days), 3 months (±7 days) after intervention initiation
Reinfection with the same microorganism
Time frame: 1 month (±3 days), 3 months (±7 days) after intervention initiation
Breach of the inner table of the skull during calvarial drilling
Breach of the inner table of the skull
Time frame: Day 1 (device placement)
Infection events related to intracalvariosseous injection, such as skin infection or calvarial bone marrow osteomyelitis
For example, skin infection or calvarial bone marrow osteomyelitis
Time frame: From Day 1 (device placement) to Day 8 (device removal)
First occurrence of seizures after intervention initiation, including seizures considered to be associated with antibiotic use
Seizures considered to be associated with antibiotic use
Time frame: From Day 1 (device placement) to Day 8 (device removal)
Nucleated cell count in calvarial bone marrow fluid before and after intracalvariosseous injection
Nucleated cell count in calvarial bone marrow fluid
Time frame: Day 1 (device placement) and Day 8 (device removal)
Hepatic or renal dysfunction/failure after intervention initiation
Definition: Hepatic dysfunction/failure is defined as alanine aminotransferase or aspartate aminotransferase levels greater than 3 times the upper limit of normal. Renal dysfunction/failure is defined as serum creatinine greater than 1.5 times the upper limit of normal or an estimated glomerular filtration rate of \<40 mL/min/1.73 m²
Time frame: From Day 1 (device placement) to Day 8 (device removal)
Incidence of sensorineural hearing loss after intervention initiation
Based on distortion-product otoacoustic emission + multiple auditory steady-state evoked responses / auditory brainstem response. Definition: Compared with baseline, hearing loss is defined as an increase of ≥20 dB at any single frequency, an increase of ≥10 dB at two adjacent frequencies, or an increase of ≥10 dB in the average threshold across three frequencies.
Time frame: From Day 1 (device placement) to Day 8 (device removal)
Incidence of red man syndrome after intervention initiation
Red man syndrome is defined as an infusion-related reaction occurring during or shortly after vancomycin administration, characterized by flushing/erythema and pruritus predominantly involving the face, neck, upper trunk, or upper extremities, with or without rash, and possibly accompanied by chest or back pain and/or hypotension, in the absence of features suggesting IgE-mediated anaphylaxis
Time frame: From Day 1 (device placement) to Day 8 (device removal)
Incidence of skin hypersensitivity reactions after intervention initiation
For example, rash and urticaria
Time frame: From Day 1 (device placement) to Day 8 (device removal)
Incidence of gastrointestinal adverse reactions after intervention initiation
For example, nausea and vomiting
Time frame: From Day 1 (device placement) to Day 8 (device removal)
Length of stay in the intensive care unit (ICU) after intervention initiation
Calculate the number of days of ICU stay
Time frame: From date of intervention initiation until first ICU discharge or death, whichever comes first, assessed up to 3 months ± 7 days
Total length of hospital stay after intervention initiation
Calculate the number of days from intervention initiation to discharge
Time frame: From date of intervention initiation until hospital discharge or death, whichever comes first, assessed up to 3 months ± 7 days
Duration of antibiotic use after intervention initiation
Calculate the number of days from intervention initiation to the discontinuation of antibiotics
Time frame: From date of intervention initiation until discontinuation of systemic antibiotic therapy or death, whichever comes first, assessed up to 3 months ± 7 days
ICU costs after intervention initiation
Costs from intervention initiation to ICU discharge
Time frame: From date of intervention initiation until first ICU discharge or death, whichever comes first, assessed up to 3 months ± 7 days
Total hospitalization costs after intervention initiation
Total cost from intervention initiation to discharge
Time frame: From date of intervention initiation until hospital discharge or death, whichever comes first, assessed up to 3 months ± 7 days
Plan to share: No
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Start is estimated for Sep 2026; primary completion for Jan 2027, 4 months later.
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yilong Wang