Blood-Brain BarrierSPARKNCT07826351

Exploring the Combination of Intracalvariosseous and 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 1 site in China.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts

Official record

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Trial summary

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: 9 participants
Where: 1 siteChina
Study dates: 21 Sep 2026to 31 Mar 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 (at least item i must be satisfied):
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.
3. No significant improvement or progressive worsening of the condition after empirical or targeted antibiotic therapy, as confirmed by at least 2 consecutive treatment evaluations, with at least one of the following: No relief or worsening of intracranial infection-related signs and symptoms; No decreasing trend in CSF white blood cell count, or re elevation after an initial decrease; No decreasing trend in CSF protein concentration, or re elevation after an initial decrease; No increasing trend in CSF/serum glucose concentration ratio, or re decrease after an initial increase; Persistently positive CSF bacterial culture, or re positivity after initial negative conversion.
4. Treatment with polymyxin B, tigecycline or vancomycin is clinically indicated for intracranial anti infective therapy, as judged by the investigator.
5. Written informed consent obtained.

Who cannot join

1. History of allergy to polymyxin B, tigecycline or vancomycin;
2. Unilateral skull craniotomy edge within 30 mm of the parietal eminence, as confirmed by cranial imaging or physical measurement;
3. Severe pulmonary infection / acute respiratory distress syndrome (PaO₂/FiO₂ < 150 mmHg, FiO₂ ≥ 0.6, PEEP ≥ 5 cmH₂O), or mechanical ventilation whose primary cause is not intracranial infection;
4. Primary extracranial focus of infection (e.g., lung, abdomen, urinary tract) requiring vasoactive agents to maintain MAP ≥ 65 mmHg (e.g., norepinephrine ≥ 0.25 μg/kg/min) and lactate > 2 mmol/L after adequate fluid resuscitation, or critical illness whose primary cause is not intracranial infection;
5. Contraindications to intracalvariosseous (ICO) administration: severe skull fracture, poor visualization of the calvarial diploic space, planned decompressive craniectomy, or other conditions that may interfere with ICO drug delivery;
6. Clinical signs of brain herniation: unilateral or bilateral pupillary dilation and fixation; loss of other brainstem reflexes judged by the investigator to be caused by meningitis or brain herniation; or other uncontrollable signs of vital sign instability;

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7. Bleeding tendency considered unfavorable for the procedure by the investigator: coagulopathy (e.g., platelet count < 50 × 10⁹/L; prothrombin time [PT] prolongation > 3 seconds), or previously diagnosed hemophilia or other coagulation disorders;
8. Severe hepatic or renal insufficiency: Severe hepatic insufficiency: alanine aminotransferase (ALT) ≥ 3 × upper limit of normal (ULN) or aspartate aminotransferase (AST) ≥ 3 × ULN; Severe renal insufficiency: serum creatinine (CRE) ≥ 1.5 × ULN or estimated glomerular filtration rate (eGFR) < 40 mL/min/1.73 m²;
9. Acute ST segment elevation myocardial infarction and/or decompensated heart failure (New York Heart Association [NYHA] class III or IV) within the past 3 months;
10. Active hepatitis B infection (positive hepatitis B surface antigen and/or serum HBV DNA positive, or serum HBV DNA > 2 × 10⁸ IU/mL);
11. Positive hepatitis C virus antibody or history of positive testing;
12. Positive HIV test or history of positive testing;
13. Pregnant, lactating, or potentially pregnant patients, or patients planning pregnancy;
14. Currently participating in other interventional trials, or having received other investigational drugs within 1 month or 5 drug half lives;
15. Patients deemed unsuitable for the study by the investigator.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Yilong Wang, PhD, MD contact

13569869755

yilong528@aliyun.com

China1 site

Beijing Tiantan Hospital, Beijing
Beijing, Beijing Municipality, 100071

Other trials in China

About this study

Official title: Feasibility, Safety, and Preliminary Efficacy of Combined Intracalvariosseous and Intravenous Antibiotic Infusion for Moderate to Severe Bacterial Meningitis

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.

Read the detailed description

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.

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 groups in NCT07826351
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 (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. Receives: Procedure: Intracalvariosseous injection vancomycin/tigecycline/polymyxin B; 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.

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.
Measured: 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
Measured: 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
Measured: Day 8, Day 15 after intervention initiation

Secondary outcomes (30)

Cure rate at Day 8 and Day 15
Definition: Proportion of participants meeting the "Cure" criteria defined above.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: Days 2-4 and Day 8, Day 15 after intervention initiation
CSF bacterial culture results and pathogen clearance status
Cerebrospinal fluid bacteriological culture results
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: From Day 1 (device placement) to Day 8 (device removal)
Incidence of skin hypersensitivity reactions after intervention initiation
For example, rash and urticaria
Measured: From Day 1 (device placement) to Day 8 (device removal)
Incidence of gastrointestinal adverse reactions after intervention initiation
For example, nausea and vomiting
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: From date of intervention initiation until hospital discharge or death, whichever comes first, assessed up to 3 months ± 7 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Sep 202631 Mar 2027

First posted17 Sep 2026
Study start21 Sep 2026 (estimated)
Primary completion31 Jan 2027 (estimated)
Study completion31 Mar 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 9 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07826351
Sponsor's protocol ID: Pre-CX25YZ07
Acronym: SPARK
Status last verified: Sep 2026
First submitted: 13 Sep 2026
Last updated: 17 Sep 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Interested in taking part?

Yilong Wang, PhD, MD

13569869755

yilong528@aliyun.com

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 17 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Feasibility, Safety, and Preliminary Efficacy of Combined Intracalvariosseous and Intravenous Antibiotic Infusion for Moderate to Severe Bacterial Meningitis
ClinicalTrials.gov ID: NCT07826351
Acronym / sponsor ID: SPARK / Pre-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: 9 participants (estimated)
Lead sponsor: yilong WangUniversity, hospital or other
Study start: 21 Sep 2026 (estimated)
Primary completion: 31 Jan 2027 (estimated)
Study completion: 31 Mar 2027 (estimated)
First posted: 17 Sep 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.

Detailed description

Study visits are scheduled at:

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

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 (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.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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 (at least item i must be satisfied):
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.

Key exclusion criteria (15 listed)

1. History of allergy to polymyxin B, tigecycline or vancomycin;
2. Unilateral skull craniotomy edge within 30 mm of the parietal eminence, as confirmed by cranial imaging or physical measurement;
3. Severe pulmonary infection / acute respiratory distress syndrome (PaO₂/FiO₂ < 150 mmHg, FiO₂ ≥ 0.6, PEEP ≥ 5 cmH₂O), or mechanical ventilation whose primary cause is not intracranial infection;
4. Primary extracranial focus of infection (e.g., lung, abdomen, urinary tract) requiring vasoactive agents to maintain MAP ≥ 65 mmHg (e.g., norepinephrine ≥ 0.25 μg/kg/min) and lactate > 2 mmol/L after adequate fluid resuscitation, or critical illness whose primary cause is not intracranial infection;
5. Contraindications to intracalvariosseous (ICO) administration: severe skull fracture, poor visualization of the calvarial diploic space, planned decompressive craniectomy, or other conditions that may interfere with ICO drug delivery;

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
Conventional treatmentStandard treatment and management according to related guidelines during the entire treatment period	Other	Intracalvariosseous injection + Intravenous injection

Primary outcome

Feasibility and safety of cranial burr hole procedure and 7-day continuous intracalvariosseous antibiotic infusion
Time frame: From Day 1 (device placement) to Day 8 (device removal)
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.
Proportion of participants requiring rescue intrathecal/intraventricular antibiotic therapy within 3 days after intervention initiation
Time frame: Within 3 days after initiation of intracalvariosseous treatment, such as Day 2, 3, 4.
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
Overall clinical response rate at Day 8 and Day 15
Time frame: Day 8, Day 15 after intervention initiation
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

30 secondary outcomes

Cure rate at Day 8 and Day 15
Time frame: Day 8, Day 15 after intervention initiation
Improvement rate at Day 8 and Day 15
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
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
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
Time frame: Days 2-4 and Day 8, Day 15 after intervention initiation
CSF bacterial culture results and pathogen clearance status
Time frame: Days 2-4 and Day 8, Day 15 after intervention initiation
Glasgow Coma Scale (GCS) score and its change from baseline
Time frame: Days 2-4 and Day 8, Day 15 after intervention initiation
All-cause mortality within 14 days of intervention initiation
Time frame: Within 14 days of the start of the intervention
Mortality due to meningitis within 14 days of intervention initiation
Time frame: Within 14 days of the start of the intervention
Antibiotic concentrations in CSF and plasma, and CSF/plasma concentration ratio
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
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
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
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
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
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
Time frame: 1 month (±3 days), 3 months (±7 days) after intervention initiation
Breach of the inner table of the skull during calvarial drilling
Time frame: Day 1 (device placement)
Infection events related to intracalvariosseous injection, such as 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
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
Time frame: Day 1 (device placement) and Day 8 (device removal)
Hepatic or renal dysfunction/failure after intervention initiation
Time frame: From Day 1 (device placement) to Day 8 (device removal)
Incidence of sensorineural hearing loss after intervention initiation
Time frame: From Day 1 (device placement) to Day 8 (device removal)
Incidence of red man syndrome after intervention initiation
Time frame: From Day 1 (device placement) to Day 8 (device removal)
Incidence of skin hypersensitivity reactions after intervention initiation
Time frame: From Day 1 (device placement) to Day 8 (device removal)
Incidence of gastrointestinal adverse reactions after intervention initiation
Time frame: From Day 1 (device placement) to Day 8 (device removal)
Length of stay in the intensive care unit (ICU) after intervention initiation
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
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
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
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
Time frame: From date of intervention initiation until hospital discharge or death, whichever comes first, assessed up to 3 months ± 7 days

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 17 Sep 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 contact

13569869755

yilong528@aliyun.com

Yilong Wang, PhD, MD principal investigator

Beijing Tiantan Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 8 inclusion and 15 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 17 Sep 2026. 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. 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?

Feasibility and safety of cranial burr hole procedure and 7-day continuous intracalvariosseous antibiotic infusion (time frame: From Day 1 (device placement) to Day 8 (device removal)). The study lists 3 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 NCT07826351.

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 17 Sep 2026.