Exploring the Combination of Intracalvariosseous and 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 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
1. Age 18-75 years, gender not limited;
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.
Disqualifiers
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;
Trial design
Design model
Single group
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
9 Participants
are divided into 1 treatment groupGroup A: Intracalvariosseous injection + Intravenous injectionExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
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)2
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, 4.3
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 initiationSecondary outcomes
1
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 initiation2
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 initiation3
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 initiation4
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 initiationSponsors 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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