NCT07495150

Intracalvariosseous Plus Intravenous Antibiotics for Moderate-to-Severe Bacterial Meningitis

Efficacy and Safety of Intracalvariosseous Combined With Intravenous Injection of Antibiotics in Moderate-to-Severe Bacterial Meningitis

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 86 (estimated)
• Sponsor: yilong Wang · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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. 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.

Conditions

• Blood-Brain Barrier
• Bacterial Meningitis

Interventions

Type	Name	Description
PROCEDURE	Intracalvariosseous injection vancomycin/tigecycline/polymyxin B	Continuous intracalvariosseous infusion of polymyxin B (12.5 mg/day), tigecycline (12.5 mg/day), and vancomycin (125 mg/day).
DRUG	Intravenous injection vancomycin/tigecycline/polymyxin B	Intravenous infusion of polymyxin B (100 mg/day), tigecycline (100 mg/day), and vancomycin (2000 mg/day).
OTHER	Conventional treatment	Standard treatment and management according to related guidelines during the entire treatment period

Timeline

• Start date: 2026-04-01
• Primary completion: 2027-04-01
• Completion: 2027-07-01
• First posted: 2026-03-27
• Last updated: 2026-03-27

Locations

6 sites across 1 country: China