Blood-Brain BarrierFLAMENCT07495150
Intracalvariosseous Plus Intravenous Antibiotics for Moderate-to-Severe Bacterial Meningitis
A study testing Intracalvariosseous injection vancomycin/tigecycline/polymyxin B, Intravenous injection vancomycin/tigecycline/polymyxin B and Conventional treatment in people with Blood-Brain Barrier and Bacterial Meningitis, run by yilong Wang at 6 sites in China.
Trial summary
Multiple preclinical and clinical studies, including the investigators' published work and the ongoing SOLUTION series, have consistently demonstrated that intracalvariosseous (ICO) injection can markedly increase drug exposure within the central nervous system with acceptable safety. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Blood-Brain Barrier, Bacterial Meningitis
- What is being tested?
- Intracalvariosseous injection vancomycin/tigecycline/polymyxin B, Intravenous injection vancomycin/tigecycline/polymyxin B and Conventional treatment
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 86 participants
- Where
- 6 sitesChina
- Study dates
- 1 Apr 2026to 1 Jul 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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. Age 18-75 years, gender not limited;
- 2. Meeting the diagnostic criteria for moderate to severe bacterial meningitis:
- Meeting the diagnostic criteria for bacterial meningitis, i.e., meeting at least item i:
- Abnormal body temperature (>38℃ or <36℃), turbid or purulent Cerebrospinal fluid (CSF) , CSF leukocytosis (>500×10⁶/L), CSF glucose/serum glucose concentration <0.4, CSF protein concentration >50mg/dL, meeting the clinical diagnosis; ii. In addition to item i, positive microbial tests or cultures of specimen smears, drainage tube heads, implants, and CSF (excluding contamination and colonization), meeting the etiological diagnosis;
- GCS score ≤12 points or a decrease of 2 points from the previous score;
- At least one of the following conditions is present: altered consciousness, seizures, brain parenchymal involvement, severe manifestations such as mechanical ventilation or circulatory support.
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- 3. After 48-72 hours of antibiotic treatment, if the investigator determines that the patient's condition shows no significant improvement or continues to worsen, or if at least one of the following conditions is present:
- Symptoms and signs related to intracranial infection show no trend of relief or worsen;
- CSF white blood cell count shows no trend of decrease, or increases after decreasing;
- CSF protein concentration shows no trend of decrease, or increases after decreasing;
- CSF/serum glucose concentration shows no trend of increase, or decreases after increasing;
- CSF bacterial culture remains positive or becomes positive again after initially being negative.
- 4. Based on the patient's condition, treatment with polymyxin B, tigecycline, or vancomycin may be necessary.
- 5. Obtain informed consent.
Who cannot join
- 1. History of allergy to polymyxin B, tigecycline, or vancomycin;
- 2. Received intrathecal or intraventricular antibiotic treatment before randomization;
- 3. Patients with severe pulmonary infection/acute respiratory distress syndrome (PaO₂/FiO₂ < 150 mmHg, FiO₂ ≥ 0.6, PEEP ≥ 5 cmH₂O) or whose primary cause of mechanical ventilation is not determined to be intracranial infection;
- 4. Patients with a primary extracranial infection focus (e.g., lungs, abdomen, urinary tract, etc.) who, after adequate fluid resuscitation, require vasoactive drugs to maintain MAP ≥ 65 mmHg (e.g., norepinephrine ≥ 0.25 μg/kg/min) and lactate > 2 mmol/L, or whose primary cause of critical illness is not determined to be intracranial infection;
- 5. Patients with contraindications to transcranial administration, such as severe skull fracture, poor visualization of the skull diploic, or planned decompressive craniectomy, which may affect transcranial administration.
- 6. Clinical signs of brain herniation, such as unilateral or bilateral pupillary dilation and fixation; or loss of other brainstem reflexes determined by the investigator to be caused by meningitis or brain herniation; or other uncontrollable signs of unstable vital signs;
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- 7. Bleeding tendency deemed unfavorable for the procedure by the investigator: abnormal coagulation function (e.g., platelet count <50×10⁹/L; prothrombin time [PT]>3s), patients with a previous diagnosis of hemophilia or other coagulation disorders;
- 8. Patients with severe hepatic or renal insufficiency (where severe hepatic insufficiency is defined as alanine aminotransferase (ALT) value ≥3 times the upper limit of normal (ULN) or aspartate aminotransferase (AST) value ≥3 times the ULN; severe renal insufficiency is defined as serum creatinine (CRE) ≥1.5 times the ULN or glomerular filtration rate (eGFR) <40 mL/min/1.73m²;
- 9. Within the past 3 months, the patient has experienced an acute ST-segment elevation myocardial infarction and/or decompensated heart failure (meeting New York Heart Association [NYHA] functional class III or IV).
- 10. Patients with severe or extremely severe anemia (hemoglobin < 60 g/L) at the time of randomization;
- 11. Patients with active hepatitis B infection (positive hepatitis B surface antigen and/or positive serum HBV DNA or serum HBV DNA > 2 × 10⁸ IU/ml);
- 12. Patients with positive hepatitis C virus antibody or a history of positive testing;
- 13. Patients with positive HIV test or a history of positive testing;
- 14. Pregnant, lactating, or potentially pregnant patients, or patients planning to become pregnant;
- 15. Patients currently participating in other interventional trials or who have used other investigational drugs within one month or five drug half-lives;
- 16. Patients deemed unsuitable for participation in this study by the investigator.
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
China6 sites
Beijing Tiantan Hospital
Beijing, Beijing Municipality, 100071
Yilong Wang, MD+PhD, 13569869755, yilong528@aliyun.com
Kaifeng Central Hospital
Kaifeng, Henan
Linyi City People Hospital
Linyi, Shandong
Tianjin Huanhu Hospital
Tianjin, Tianjin Municipality, 300000
The First Affiliated Hospital of Xinxiang Medical University
Xinxiang, Henan
Henan Provincial People's Hospital
Zhengzhou, Henan, 450000
Guang Feng
About this study
Official title: Efficacy and Safety of Intracalvariosseous Combined With Intravenous Injection of Antibiotics in Moderate-to-Severe Bacterial Meningitis
Multiple preclinical and clinical studies, including the investigators' published work and the ongoing SOLUTION series, have consistently demonstrated that intracalvariosseous (ICO) injection can markedly increase drug exposure within the central nervous system with acceptable safety. This trial is designed to further evaluate the efficacy and safety of antibiotic delivery via the ICO route in the treatment of bacterial meningitis, particularly in patients with moderate-to-severe disease who have shown an inadequate response to standard therapy.
Read the detailed description
Bacterial meningitis remains a major cause of death and neurological disability despite advances in antimicrobial therapy, vaccination, and critical care. Moderate-to-severe disease, particularly healthcare-associated infection and cases caused by multidrug-resistant pathogens, continues to pose substantial therapeutic challenges because intravenous antibiotic therapy alone may not achieve sufficiently rapid or sustained drug exposure in cerebrospinal fluid and at the meningeal surface. Although intrathecal and intraventricular administration can increase local drug concentrations, these approaches are invasive and have limited diffusion.
Anatomical and physiological studies have demonstrated communication among calvarial bone marrow, dura, cerebrospinal fluid spaces, and glymphatic pathways, supporting the rationale for intracalvariosseous (ICO) injection as a regional route for drug delivery to the central nervous system. Preclinical and clinical studies, including the investigators' published work and the ongoing SOLUTION series, suggest that ICO injection can enhance local central nervous system drug exposure with an acceptable safety profile. In addition, an exploratory study conducted by the investigators, using vancomycin administered via ICO injection in an experimental animal model of bacterial meningitis, further supported the potential of this route to improve anti-infective efficacy.
This trial is a multicenter, prospective, randomized, open-label, blinded-endpoint study comparing ICO injection plus intravenous antibiotic therapy with intravenous antibiotic therapy alone.
The study aims to evaluate differences in efficacy and safety between combined treatment with ICO injection and intravenous antibiotics versus intravenous antibiotics alone in participants with moderate-to-severe bacterial meningitis who have shown a suboptimal response to treatment.
Participants with moderate-to-severe bacterial meningitis and inadequate improvement after 48-72 hours of initial intravenous treatment will be randomized in a 1:1 ratio.
In the intervention group, bilateral parietal ICO access devices will be placed, and the selected antibiotic will be continuously administered through the calvarial bone marrow route for 7 days while the same antibiotic is also given intravenously.
In the control group, treatment will consist of intravenous antibiotic therapy alone.
Guideline-based supportive care, including intracranial pressure management, seizure control, organ support, and other standard measures, will be provided in both groups.
Face-to-face visits will be conducted at randomization (baseline), 48-72 hours, Day 5, Day 8, Day 10, Day 14, Day 30 (±3 days), or on the day of discharge. A telephone follow-up visit will be conducted at Month 3 (±7 days).
A Data and Safety Monitoring Board (DSMB) will regularly monitor safety throughout the study. The trial has been approved by the Institutional Review Board (IRB) and Ethics Committee (EC) of Beijing Tiantan Hospital, Capital Medical University.
- Conditions
- Blood-Brain Barrier, Bacterial Meningitis
- Being tested
- Intracalvariosseous injection vancomycin/tigecycline/polymyxin B, Intravenous injection vancomycin/tigecycline/polymyxin B, Conventional treatment
- Keywords
- Blood-Brain Barrier, Bacterial meningitis, Prognosis, Intracalvariosseous, Antibiotic
- Medical subject headings
- Meningitis, Bacterial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intracalvariosseous injection vancomycin/tigecycline/polymyxin BProcedure or surgery
Continuous intracalvariosseous infusion of polymyxin B (12.5 mg/day), tigecycline (12.5 mg/day), and vancomycin (125 mg/day).
Intravenous injection vancomycin/tigecycline/polymyxin BDrug
Intravenous infusion of polymyxin B (100 mg/day), tigecycline (100 mg/day), and vancomycin (2000 mg/day).
Conventional treatmentOther
Standard treatment and management according to related guidelines during the entire treatment period
| Study group | Role | What they receive |
|---|---|---|
| Intracalvariosseous injection + Intravenous injection | Experimental | 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 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. If a change in antibiotic selection is required during the period of combined treatment, the antibiotic administered via the intracalvariosseous route must remain consistent with that administered intravenously. Receives: Procedure: Intracalvariosseous injection vancomycin/tigecycline/polymyxin B; Drug: Intravenous injection vancomycin/tigecycline/polymyxin B; Other: Conventional treatment |
| Intravenous injection | Active comparator | 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). The duration of intravenous therapy will be adjusted according to treatment response, including clinical symptoms, signs, and laboratory findings. Receives: Drug: Intravenous injection vancomycin/tigecycline/polymyxin B; Other: Conventional treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall effective rate after 7 days of randomization
Overall effective rate = [(Cure + Improvement) / Total Number of Case] * 100% Cure: Cerebrospinal fluid (CSF) white blood cell count, CSF protein concentration, CSF/serum glucose ratio, and CSF bacterial culture are all normal in three consecutive tests.
Improvement: At least one of the following three CSF white blood cell counts, CSF protein concentration, CSF/serum glucose ratio, and CSF bacterial culture is normal.
Ineffective: All three of the following CSF white blood cell counts, CSF protein concentration, CSF/serum glucose ratio, and CSF bacterial culture are abnormal.
Normal Reference Values for CSF Indicators: white blood cell count < 100 × 10⁶/L, protein concentration < 50 mg/dL, CSF/serum glucose ratio > 0.5.
Measured: 8,10 and 14 days after randomization
Secondary outcomes (10)
Cure rate after 7 days of randomization
Cure: Cerebrospinal fluid (CSF) white blood cell count, CSF protein concentration, CSF/serum glucose ratio, and CSF bacterial culture are all normal in three consecutive tests.
Reference Values for CSF Indicators: white blood cell count < 100 × 10⁶/L, protein concentration < 50 mg/dL, CSF/serum glucose ratio > 0.5.
Measured: 8,10 and 14 days after randomization
Improvement rate after 7 days of randomization
Improvement: At least one of the following three CSF white blood cell counts, CSF protein concentration, CSF/serum glucose ratio, and CSF bacterial culture is normal.
Reference Values for CSF Indicators: white blood cell count < 100 × 10⁶/L, protein concentration < 50 mg/dL, CSF/serum glucose ratio > 0.5.
Measured: 8,10 and 14 days after randomization
Cerebrospinal fluid white blood cell count at 48-72 hours and Days 5, 8, 10, and 14 after randomization
Cerebrospinal fluid white blood cell count
Measured: 48-72 hours after randomization, Days 5, 8, 10, and 14 after randomization
Cerebrospinal fluid protein concentration at 48-72 hours and Days 5, 8, 10, and 14 after randomization
Cerebrospinal fluid protein concentration
Measured: 48-72 hours after randomization, Days 5, 8, 10, and 14 after randomization
Cerebrospinal fluid-to-serum glucose concentration ratio at 48-72 hours and Days 5, 8, 10, and 14 after randomization
Cerebrospinal fluid-to-serum glucose concentration ratio
Measured: 48-72 hours after randomization, Days 5, 8, 10, and 14 after randomization
Cerebrospinal fluid bacteriological culture results at 48-72 hours and Days 5, 8, 10, and 14 after randomization
Cerebrospinal fluid bacteriological culture results
Measured: 48-72 hours after randomization, Days 5, 8, 10, and 14 after randomization
Glasgow Coma Scale (GCS) scores at 48-72 hours and Days 5, 8, 10, and 14 after randomization
Glasgow Coma Scale (GCS) is a neurological scale that assesses level of consciousness using 3 components: eye opening, verbal response, and motor response. The total score ranges from 3 to 15, with higher scores indicating a better neurological outcome / level of consciousness and lower scores indicating a worse outcome / deeper impairment of consciousness.
Measured: 48-72 hours after randomization, Days 5, 8, 10, and 14 after randomization
Proportion of participants who require conversion to intrathecal or intraventricular antibiotic therapy during the 48-72 hour period after randomization
This proportion is defined as the number of participants who are evaluated during the 48-72-hour period after randomization and are judged to have an unsatisfactory treatment response requiring conversion to intrathecal or intraventricular antibiotic therapy, divided by the total number of participants in the corresponding treatment group. An unsatisfactory treatment response is defined as the absence of an improving trend, compared with baseline, in cerebrospinal fluid white blood cell count, protein concentration, and cerebrospinal fluid-to-serum glucose concentration ratio.
Measured: During the 48-72 hour period after randomization
All-cause mortality from baseline to 14-day
All-cause mortality
Measured: Baseline to Day 14
Mortality due to meningitis from baseline to 14-day
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.
Measured: Baseline to Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2026
- Study start1 Apr 2026 (estimated)
- Primary completion1 Apr 2027 (estimated)
- Study completion1 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Blood-Brain BarrierStudies of the same condition, open and under way.
- 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
- 86 participants (estimated)
Sponsor and investigators
- Lead sponsor
- yilong Wang
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, yilong Wang, Beijing Tiantan Hospital
- Investigators
- Yilong Wang, PhD+MD, Principal investigator, Beijing Tiantan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07495150
- Sponsor's protocol ID
- CX25YZ07
- Acronym
- FLAME
- Status last verified
- Mar 2026
- First submitted
- 9 Mar 2026
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Intracalvariosseous Combined With Intravenous Injection of Antibiotics in Moderate-to-Severe Bacterial Meningitis
- ClinicalTrials.gov ID
- NCT07495150
- Acronym / sponsor ID
- FLAME / CX25YZ07
- Conditions
- Blood-Brain Barrier, Bacterial Meningitis
- Keywords
- Blood-Brain Barrier, Bacterial meningitis, Prognosis, Intracalvariosseous, Antibiotic
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 86 participants (estimated)
- Lead sponsor
- yilong WangUniversity, hospital or other
- Study start
- 1 Apr 2026 (estimated)
- Primary completion
- 1 Apr 2027 (estimated)
- Study completion
- 1 Jul 2027 (estimated)
- First posted
- 27 Mar 2026 (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.
Multiple preclinical and clinical studies, including the investigators' published work and the ongoing SOLUTION series, have consistently demonstrated that intracalvariosseous (ICO) injection can markedly increase drug exposure within the central nervous system with acceptable safety. This trial is designed to further evaluate the efficacy and safety of antibiotic delivery via the ICO route in the treatment of bacterial meningitis, particularly in patients with moderate-to-severe disease who have shown an inadequate response to standard therapy.
Detailed description
Bacterial meningitis remains a major cause of death and neurological disability despite advances in antimicrobial therapy, vaccination, and critical care. Moderate-to-severe disease, particularly healthcare-associated infection and cases caused by multidrug-resistant pathogens, continues to pose substantial therapeutic challenges because intravenous antibiotic therapy alone may not achieve sufficiently rapid or sustained drug exposure in cerebrospinal fluid and at the meningeal surface. Although intrathecal and intraventricular administration can increase local drug concentrations, these approaches are invasive and have limited diffusion.
Anatomical and physiological studies have demonstrated communication among calvarial bone marrow, dura, cerebrospinal fluid spaces, and glymphatic pathways, supporting the rationale for intracalvariosseous (ICO) injection as a regional route for drug delivery to the central nervous system. Preclinical and clinical studies, including the investigators' published work and the ongoing SOLUTION series, suggest that ICO injection can enhance local central nervous system drug exposure with an acceptable safety profile. In addition, an exploratory study conducted by the investigators, using vancomycin administered via ICO injection in an experimental animal model of bacterial meningitis, further supported the potential of this route to improve anti-infective efficacy.
This trial is a multicenter, prospective, randomized, open-label, blinded-endpoint study comparing ICO injection plus intravenous antibiotic therapy with intravenous antibiotic therapy alone.
The study aims to evaluate differences in efficacy and safety between combined treatment with ICO injection and intravenous antibiotics versus intravenous antibiotics alone in participants with moderate-to-severe bacterial meningitis who have shown a suboptimal response to treatment.
Participants with moderate-to-severe bacterial meningitis and inadequate improvement after 48-72 hours of initial intravenous treatment will be randomized in a 1:1 ratio.
In the intervention group, bilateral parietal ICO access devices will be placed, and the selected antibiotic will be continuously administered through the calvarial bone marrow route for 7 days while the same antibiotic is also given intravenously.
In the control group, treatment will consist of intravenous antibiotic therapy alone.
Guideline-based supportive care, including intracranial pressure management, seizure control, organ support, and other standard measures, will be provided in both groups.
Face-to-face visits will be conducted at randomization (baseline), 48-72 hours, Day 5, Day 8, Day 10, Day 14, Day 30 (±3 days), or on the day of discharge. A telephone follow-up visit will be conducted at Month 3 (±7 days).
A Data and Safety Monitoring Board (DSMB) will regularly monitor safety throughout the study. The trial has been approved by the Institutional Review Board (IRB) and Ethics Committee (EC) of Beijing Tiantan Hospital, Capital Medical University.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intracalvariosseous injection + Intravenous injection | Experimental | Procedure: Intracalvariosseous injection vancomycin/tigecycline/polymyxin B, Drug: Intravenous injection vancomycin/tigecycline/polymyxin B, Other: Conventional treatmentIn 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 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. If a change in antibiotic selection is required during the period of combined treatment, the antibiotic administered via the intracalvariosseous route must remain consistent with that administered intravenously. |
| Intravenous injection | Active comparator | Drug: Intravenous injection vancomycin/tigecycline/polymyxin B, Other: Conventional treatmentIn 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). The duration of intravenous therapy will be adjusted according to treatment response, including clinical symptoms, signs, and laboratory findings. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 1. Age 18-75 years, gender not limited;
- 2. Meeting the diagnostic criteria for moderate to severe bacterial meningitis:
- 3. After 48-72 hours of antibiotic treatment, if the investigator determines that the patient's condition shows no significant improvement or continues to worsen, or if at least one of the following conditions is present:
- 4. Based on the patient's condition, treatment with polymyxin B, tigecycline, or vancomycin may be necessary.
- 5. Obtain informed consent.
Key exclusion criteria (16 listed)
- 1. History of allergy to polymyxin B, tigecycline, or vancomycin;
- 2. Received intrathecal or intraventricular antibiotic treatment before randomization;
- 3. Patients with severe pulmonary infection/acute respiratory distress syndrome (PaO₂/FiO₂ < 150 mmHg, FiO₂ ≥ 0.6, PEEP ≥ 5 cmH₂O) or whose primary cause of mechanical ventilation is not determined to be intracranial infection;
- 4. Patients with a primary extracranial infection focus (e.g., lungs, abdomen, urinary tract, etc.) who, after adequate fluid resuscitation, require vasoactive drugs to maintain MAP ≥ 65 mmHg (e.g., norepinephrine ≥ 0.25 μg/kg/min) and lactate > 2 mmol/L, or whose primary cause of critical illness is not determined to be intracranial infection;
- 5. Patients with contraindications to transcranial administration, such as severe skull fracture, poor visualization of the skull diploic, or planned decompressive craniectomy, which may affect transcranial administration.
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 |
|---|---|---|
| Intracalvariosseous injection vancomycin/tigecycline/polymyxin BContinuous intracalvariosseous infusion of polymyxin B (12.5 mg/day), tigecycline (12.5 mg/day), and vancomycin (125 mg/day). | Procedure or surgery | Intracalvariosseous injection + Intravenous injection |
| Intravenous injection vancomycin/tigecycline/polymyxin BIntravenous infusion of polymyxin B (100 mg/day), tigecycline (100 mg/day), and vancomycin (2000 mg/day). | Drug | Intracalvariosseous injection + Intravenous injection, Intravenous injection |
| Conventional treatmentStandard treatment and management according to related guidelines during the entire treatment period | Other | Intracalvariosseous injection + Intravenous injection, Intravenous injection |
Primary outcome
Overall effective rate after 7 days of randomization
Time frame: 8,10 and 14 days after randomization
Overall effective rate = [(Cure + Improvement) / Total Number of Case] * 100% Cure: Cerebrospinal fluid (CSF) white blood cell count, CSF protein concentration, CSF/serum glucose ratio, and CSF bacterial culture are all normal in three consecutive tests. Improvement: At least one of the following three CSF white blood cell counts, CSF protein concentration, CSF/serum glucose ratio, and CSF bacterial culture is normal. Ineffective: All three of the following CSF white blood cell counts, CSF protein concentration, CSF/serum glucose ratio, and CSF bacterial culture are abnormal. Normal Reference Values for CSF Indicators: white blood cell count < 100 × 10⁶/L, protein concentration < 50 mg/dL, CSF/serum glucose ratio > 0.5.
10 secondary outcomes
Cure rate after 7 days of randomization
Time frame: 8,10 and 14 days after randomization
Improvement rate after 7 days of randomization
Time frame: 8,10 and 14 days after randomization
Cerebrospinal fluid white blood cell count at 48-72 hours and Days 5, 8, 10, and 14 after randomization
Time frame: 48-72 hours after randomization, Days 5, 8, 10, and 14 after randomization
Cerebrospinal fluid protein concentration at 48-72 hours and Days 5, 8, 10, and 14 after randomization
Time frame: 48-72 hours after randomization, Days 5, 8, 10, and 14 after randomization
Cerebrospinal fluid-to-serum glucose concentration ratio at 48-72 hours and Days 5, 8, 10, and 14 after randomization
Time frame: 48-72 hours after randomization, Days 5, 8, 10, and 14 after randomization
Cerebrospinal fluid bacteriological culture results at 48-72 hours and Days 5, 8, 10, and 14 after randomization
Time frame: 48-72 hours after randomization, Days 5, 8, 10, and 14 after randomization
Glasgow Coma Scale (GCS) scores at 48-72 hours and Days 5, 8, 10, and 14 after randomization
Time frame: 48-72 hours after randomization, Days 5, 8, 10, and 14 after randomization
Proportion of participants who require conversion to intrathecal or intraventricular antibiotic therapy during the 48-72 hour period after randomization
Time frame: During the 48-72 hour period after randomization
All-cause mortality from baseline to 14-day
Time frame: Baseline to Day 14
Mortality due to meningitis from baseline to 14-day
Time frame: Baseline to Day 14
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2026.
- 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.
Yilong Wang, PhD+MD principal investigator
Beijing Tiantan Hospital
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intracalvariosseous injection vancomycin/tigecycline/polymyxin B, Intravenous injection vancomycin/tigecycline/polymyxin B and Conventional treatment in people with Blood-Brain Barrier and Bacterial Meningitis, run by yilong Wang at 6 sites 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 14 inclusion and 16 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: opening soon, as of the sponsor's last update on 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites 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. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yilong Wang, PhD+MD (13569869755, yilong528@aliyun.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall effective rate after 7 days of randomization (time frame: 8,10 and 14 days after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Mar 2026.