[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100656427":3},{"organization":4,"outcomesModule":7,"designInfo":121,"detailedDescription":127,"studyPopulation":120,"armGroups":128,"interventions":137,"overallOfficials":152,"centralContacts":156,"locations":161,"responsibleParty":175,"collaborators":120,"id":179,"slug":180,"hasResults":181,"nctId":182,"briefTitle":183,"officialTitle":184,"acronym":185,"eligibilityCriteria":186,"healthyVolunteers":181,"sex":187,"minAge":188,"maxAge":189,"enrollmentInfo":190,"targetDuration":120,"studyType":193,"phases":194,"briefSummary":195,"conditions":196,"keywords":199,"overallStatus":204,"whyStopped":120,"lastUpdateSubmitDate":205,"lastUpdatePostDateStruct":206,"startDateStruct":209,"completionDateStruct":211,"leadSponsor":213,"locationsCount":214},{"fullName":5,"class":6},"Beijing Tiantan Hospital","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":21,"otherOutcomes":120},[9,13,17],{"measure":10,"description":11,"timeFrame":12},"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.","From Day 1 (device placement) to Day 8 (device removal)",{"measure":14,"description":15,"timeFrame":16},"Proportion of participants requiring rescue intrathecal\u002Fintraventricular 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.\n\nInadequate 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:\n\nIntracranial infection-related clinical signs and symptoms Cerebrospinal fluid (CSF) white blood cell count CSF protein concentration CSF\u002Fserum glucose concentration ratio","Within 3 days after initiation of intracalvariosseous treatment, such as Day 2, 3, 4.",{"measure":18,"description":19,"timeFrame":20},"Overall clinical response rate at Day 8 and Day 15","Overall response rate = \\[(Cure + Improvement) \u002F Total number of evaluable participants\\] × 100% Cure: CSF white blood cell count, CSF protein concentration, CSF\u002Fserum glucose ratio, and CSF bacterial culture are all normal in 2 consecutive tests.\n\nImprovement: All 4 above CSF indicators are normal in at least 1 test. Ineffective: All 4 above CSF indicators remain abnormal in 2 consecutive tests.\n\nNormal reference values for CSF indicators:\n\nWhite blood cell count: \\\u003C 100 × 10⁶\u002FL Protein concentration: \\\u003C 50 mg\u002FdL CSF\u002Fserum glucose ratio: \\> 0.5","Day 8, Day 15 after intervention initiation",[22,25,28,32,35,38,41,44,48,51,55,59,63,66,68,71,74,78,81,84,87,90,93,96,99,102,106,110,114,117],{"measure":23,"description":24,"timeFrame":20},"Cure rate at Day 8 and Day 15","Definition: Proportion of participants meeting the \"Cure\" criteria defined above.",{"measure":26,"description":27,"timeFrame":20},"Improvement rate at Day 8 and Day 15","Definition: Proportion of participants meeting the \"Improvement\" criteria defined above.",{"measure":29,"description":30,"timeFrame":31},"Cerebrospinal fluid white blood cell count at Days 2-4 and Day 8, Day 15 after intervention initiation","Cerebrospinal fluid white blood cell count","Days 2-4 and Day 8, Day 15 after intervention initiation",{"measure":33,"description":34,"timeFrame":31},"Cerebrospinal fluid protein concentration at Days 2-4 and Day 8, Day 15 after intervention initiation","Cerebrospinal fluid protein concentration",{"measure":36,"description":37,"timeFrame":31},"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",{"measure":39,"description":40,"timeFrame":31},"CSF bacterial culture results and pathogen clearance status","Cerebrospinal fluid bacteriological culture results",{"measure":42,"description":43,"timeFrame":31},"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.",{"measure":45,"description":46,"timeFrame":47},"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","Within 14 days of the start of the intervention",{"measure":49,"description":50,"timeFrame":47},"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.",{"measure":52,"description":53,"timeFrame":54},"Antibiotic concentrations in CSF and plasma, and CSF\u002Fplasma concentration ratio","The ratio of cerebrospinal fluid drug concentration to plasma drug concentration","0.25, 0.5, 1, 2, 4, 8, 12, 24 hours and Days 2-4, Day 8 after intervention initiation.",{"measure":56,"description":57,"timeFrame":58},"Bacterial culture results of calvarial bone marrow fluid before and after intracalvariosseous treatment","calvarial bone marrow fluid bacteriological culture results","Day 1 (device placement) and Day 8 (device removal)",{"measure":60,"description":61,"timeFrame":62},"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","1 month (±3 days), 3 months (±7 days) after intervention initiation",{"measure":64,"description":65,"timeFrame":62},"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.",{"measure":67,"description":46,"timeFrame":62},"All-cause mortality at 1 month (±3 days), 3 months (±7 days) after intervention initiation",{"measure":69,"description":70,"timeFrame":62},"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.",{"measure":72,"description":73,"timeFrame":62},"Reinfection with the same microorganism occurred at 1 month (±3 days), 3 months (±7 days) after intervention initiation","Reinfection with the same microorganism",{"measure":75,"description":76,"timeFrame":77},"Breach of the inner table of the skull during calvarial drilling","Breach of the inner table of the skull","Day 1 (device placement)",{"measure":79,"description":80,"timeFrame":12},"Infection events related to intracalvariosseous injection, such as skin infection or calvarial bone marrow osteomyelitis","For example, skin infection or calvarial bone marrow osteomyelitis",{"measure":82,"description":83,"timeFrame":12},"First occurrence of seizures after intervention initiation, including seizures considered to be associated with antibiotic use","Seizures considered to be associated with antibiotic use",{"measure":85,"description":86,"timeFrame":58},"Nucleated cell count in calvarial bone marrow fluid before and after intracalvariosseous injection","Nucleated cell count in calvarial bone marrow fluid",{"measure":88,"description":89,"timeFrame":12},"Hepatic or renal dysfunction\u002Ffailure after intervention initiation","Definition: Hepatic dysfunction\u002Ffailure is defined as alanine aminotransferase or aspartate aminotransferase levels greater than 3 times the upper limit of normal. Renal dysfunction\u002Ffailure is defined as serum creatinine greater than 1.5 times the upper limit of normal or an estimated glomerular filtration rate of \\\u003C40 mL\u002Fmin\u002F1.73 m²",{"measure":91,"description":92,"timeFrame":12},"Incidence of sensorineural hearing loss after intervention initiation","Based on distortion-product otoacoustic emission + multiple auditory steady-state evoked responses \u002F 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.",{"measure":94,"description":95,"timeFrame":12},"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\u002Ferythema 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\u002For hypotension, in the absence of features suggesting IgE-mediated anaphylaxis",{"measure":97,"description":98,"timeFrame":12},"Incidence of skin hypersensitivity reactions after intervention initiation","For example, rash and urticaria",{"measure":100,"description":101,"timeFrame":12},"Incidence of gastrointestinal adverse reactions after intervention initiation","For example, nausea and vomiting",{"measure":103,"description":104,"timeFrame":105},"Length of stay in the intensive care unit (ICU) after intervention initiation","Calculate the number of days of ICU stay","From date of intervention initiation until first ICU discharge or death, whichever comes first, assessed up to 3 months ± 7 days",{"measure":107,"description":108,"timeFrame":109},"Total length of hospital stay after intervention initiation","Calculate the number of days from intervention initiation to discharge","From date of intervention initiation until hospital discharge or death, whichever comes first, assessed up to 3 months ± 7 days",{"measure":111,"description":112,"timeFrame":113},"Duration of antibiotic use after intervention initiation","Calculate the number of days from intervention initiation to the discontinuation of antibiotics","From date of intervention initiation until discontinuation of systemic antibiotic therapy or death, whichever comes first, assessed up to 3 months ± 7 days",{"measure":115,"description":116,"timeFrame":105},"ICU costs after intervention initiation","Costs from intervention initiation to ICU discharge",{"measure":118,"description":119,"timeFrame":109},"Total hospitalization costs after intervention initiation","Total cost from intervention initiation to discharge",null,{"allocation":122,"interventionModel":123,"interventionModelDescription":120,"primaryPurpose":124,"observationalModel":120,"timePerspective":120,"maskingInfo":125},"NA","SINGLE_GROUP","TREATMENT",{"masking":126,"maskingDescription":120,"whoMasked":120},"NONE","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\u002Fmeningitis 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.\n\nAnatomical 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.\n\nThis 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.\n\nEligible 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.\n\nAll 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.\n\nStudy visits are scheduled at:\n\nBaseline (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 \u002F Ethics Committee of Beijing Tiantan Hospital, Capital Medical University.",[129],{"label":130,"type":131,"description":132,"interventionNames":133},"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.",[134,135,136],"Procedure: Intracalvariosseous injection vancomycin\u002Ftigecycline\u002Fpolymyxin B","Drug: Intravenous injection vancomycin\u002Ftigecycline\u002Fpolymyxin B","Other: Conventional treatment",[138,143,148],{"type":139,"name":140,"description":141,"armGroupLabels":142,"otherNames":120},"PROCEDURE","Intracalvariosseous injection vancomycin\u002Ftigecycline\u002Fpolymyxin B","Continuous intracalvariosseous infusion of polymyxin B (12.5 mg\u002Fday), tigecycline (12.5 mg\u002Fday), and vancomycin (125 mg\u002Fday).",[130],{"type":144,"name":145,"description":146,"armGroupLabels":147,"otherNames":120},"DRUG","Intravenous injection vancomycin\u002Ftigecycline\u002Fpolymyxin B","Intravenous infusion of polymyxin B (100 mg\u002Fday), tigecycline (100 mg\u002Fday), and vancomycin (2000 mg\u002Fday).",[130],{"type":6,"name":149,"description":150,"armGroupLabels":151,"otherNames":120},"Conventional treatment","Standard treatment and management according to related guidelines during the entire treatment period",[130],[153],{"name":154,"affiliation":5,"role":155},"Yilong Wang, PhD, MD","PRINCIPAL_INVESTIGATOR",[157],{"name":154,"role":158,"phone":159,"phoneExt":120,"email":160},"CONTACT","13569869755","yilong528@aliyun.com",[162],{"facility":163,"status":120,"city":164,"state":165,"zip":166,"country":167,"countryCode":168,"cosmosGeoPoint":169,"geoPoint":174,"contacts":120},"Beijing Tiantan Hospital, Beijing","Beijing","Beijing Municipality","100071","China","CN",{"type":170,"coordinates":171},"Point",[172,173],116.39723,39.9075,{"lat":173,"lon":172},{"type":176,"investigatorFullName":177,"investigatorTitle":178,"investigatorAffiliation":5,"oldNameTitle":120,"oldOrganization":120},"SPONSOR_INVESTIGATOR","yilong Wang","Vice President of Beijing Tiantan Hospital","100656427","exploring-the-combination-of-intracalvariosseous-and-intravenous-antibiotics-for-moderate-to-severe-bacterial-meningitis-100656427",false,"NCT07826351","Exploring the Combination of Intracalvariosseous and Intravenous Antibiotics for Moderate to Severe Bacterial Meningitis","Feasibility, Safety, and Preliminary Efficacy of Combined Intracalvariosseous and Intravenous Antibiotic Infusion for Moderate to Severe Bacterial Meningitis","SPARK","Inclusion Criteria:\n\n* 1\\. Age 18-75 years, gender not limited;\n* 2\\. Meeting the diagnostic criteria for moderate-to-severe bacterial meningitis:\n\nMeeting the diagnostic criteria for bacterial meningitis (at least item i must be satisfied):\n\ni. Clinical diagnosis: abnormal body temperature (\\>38 ℃ or \\\u003C36 ℃), turbid or purulent cerebrospinal fluid (CSF), CSF leukocytosis (\\>500 × 10⁶\u002FL), CSF glucose\u002Fserum glucose ratio \\\u003C 0.4, CSF protein concentration \\> 50 mg\u002FdL; 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).\n\nGlasgow 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.\n\n* 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\u002Fserum glucose concentration ratio, or re decrease after an initial increase; Persistently positive CSF bacterial culture, or re positivity after initial negative conversion.\n* 4\\. Treatment with polymyxin B, tigecycline or vancomycin is clinically indicated for intracranial anti infective therapy, as judged by the investigator.\n* 5\\. Written informed consent obtained.\n\nExclusion Criteria:\n\n* 1\\. History of allergy to polymyxin B, tigecycline or vancomycin;\n* 2\\. Unilateral skull craniotomy edge within 30 mm of the parietal eminence, as confirmed by cranial imaging or physical measurement;\n* 3\\. Severe pulmonary infection \u002F acute respiratory distress syndrome (PaO₂\u002FFiO₂ \\\u003C 150 mmHg, FiO₂ ≥ 0.6, PEEP ≥ 5 cmH₂O), or mechanical ventilation whose primary cause is not intracranial infection;\n* 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\u002Fkg\u002Fmin) and lactate \\> 2 mmol\u002FL after adequate fluid resuscitation, or critical illness whose primary cause is not intracranial infection;\n* 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;\n* 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;\n* 7\\. Bleeding tendency considered unfavorable for the procedure by the investigator: coagulopathy (e.g., platelet count \\\u003C 50 × 10⁹\u002FL; prothrombin time \\[PT\\] prolongation \\> 3 seconds), or previously diagnosed hemophilia or other coagulation disorders;\n* 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) \\\u003C 40 mL\u002Fmin\u002F1.73 m²;\n* 9\\. Acute ST segment elevation myocardial infarction and\u002For decompensated heart failure (New York Heart Association \\[NYHA\\] class III or IV) within the past 3 months;\n* 10\\. Active hepatitis B infection (positive hepatitis B surface antigen and\u002For serum HBV DNA positive, or serum HBV DNA \\> 2 × 10⁸ IU\u002FmL);\n* 11\\. Positive hepatitis C virus antibody or history of positive testing;\n* 12\\. Positive HIV test or history of positive testing;\n* 13\\. Pregnant, lactating, or potentially pregnant patients, or patients planning pregnancy;\n* 14\\. Currently participating in other interventional trials, or having received other investigational drugs within 1 month or 5 drug half lives;\n* 15\\. Patients deemed unsuitable for the study by the investigator.","ALL","18 Years","75 Years",{"count":191,"type":192},9,"ESTIMATED","INTERVENTIONAL",[122],"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.",[197,198],"Blood-Brain Barrier","Bacterial Meningitis",[197,200,201,202,203],"Bacterial meningitis","Prognosis","Intracalvariosseous","Antibiotic","NOT_YET_RECRUITING","2026-09-13",{"date":207,"type":208},"2026-09-17","ACTUAL",{"date":210,"type":192},"2026-09-21",{"date":212,"type":192},"2027-03-31",{"name":177,"class":6},1]