Intracalvariosseous Plus Intravenous Antibiotics for Moderate-to-Severe Bacterial Meningitis
Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-75
Sponsoryilong Wang
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
1. Age 18-75 years, gender not limited;
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.
Symptoms and signs related to intracranial infection show no trend of relief or worsen;
Disqualifiers
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;
Trial design
Design model
Parallel
Treatments tested in this trial
Intracalvariosseous injection vancomycin/tigecycline/polymyxin B
Procedure/SurgeryContinuous intracalvariosseous infusion of polymyxin B (12.5 mg/day), tigecycline (12.5 mg/day), and vancomycin (125 mg/day).
Intravenous injection vancomycin/tigecycline/polymyxin B
DrugIntravenous infusion of polymyxin B (100 mg/day), tigecycline (100 mg/day), and vancomycin (2000 mg/day).
Conventional treatment
Other interventionStandard treatment and management according to related guidelines during the entire treatment period
Treatment groups
86 Participants
are divided into 2 treatment groupsGroup A: Intracalvariosseous injection + Intravenous injectionExperimental treatment 3 interventions
Group B: Intravenous injectionActive comparator 2 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
8,10 and 14 days after randomizationSecondary outcomes
1
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.
Time frame
8,10 and 14 days after randomization2
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.
Time frame
8,10 and 14 days after randomization3
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
Time frame
48-72 hours after randomization, Days 5, 8, 10, and 14 after randomization4
Cerebrospinal fluid protein concentration at 48-72 hours and Days 5, 8, 10, and 14 after randomization
Cerebrospinal fluid protein concentration
Time frame
48-72 hours after randomization, Days 5, 8, 10, and 14 after randomizationOther outcomes
1
The ratio of the concentrations of the antibiotics used after randomization in cerebrospinal fluid and plasma
The ratio of cerebrospinal fluid drug concentration to plasma drug concentration
Time frame
0.25, 0.5, 1, 2, 4, 8, 12, 24 hours after randomization2
Glasgow Outcome Scale (GOS) scores at 1 month ± 3 days (or on the day of discharge) and at 3 months ± 7 days after randomization
Glasgow Outcome Scale (GOS) is a 5-point functional outcome scale used to assess recovery after brain injury or severe neurological disease. The total score ranges from 1 to 5, where 1 = death, 2 = vegetative state, 3 = severe disability, 4 = moderate disability, and 5 = good recovery; therefore, higher scores indicate a better outcome and lower scores indicate a worse outcome.
Time frame
1 month ± 3 days (or on the day of discharge) and at 3 months ± 7 days after randomization3
Cure rate without neurological sequelae at 1 month ± 3 days (or on the day of discharge) and at 3 months ± 7 days after randomization
Cure rate without neurological sequelae：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, and were not accompanied by neurological symptoms attributable to meningitis at baseline. 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
1 month ± 3 days (or on the day of discharge) and at 3 months ± 7 days after randomization4
All-cause mortality rate at 1 month ± 3 days (or on the day of discharge) and at 3 months ± 7 days after randomization
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 (or on the day of discharge) and at 3 months ± 7 days after randomizationSponsors and contacts
Click on the lead sponsor to view all of their trials.
yilong Wang
Lead sponsor
Beijing Tiantan Hospital
Sponsor institution
Source ClinicalTrials.gov
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