[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100631013":3},{"organization":4,"armGroups":7,"interventions":21,"overallOfficials":37,"centralContacts":41,"locations":46,"responsibleParty":110,"collaborators":27,"id":114,"slug":115,"hasResults":116,"nctId":117,"briefTitle":118,"officialTitle":119,"acronym":120,"eligibilityCriteria":121,"healthyVolunteers":116,"sex":122,"minAge":123,"maxAge":124,"enrollmentInfo":125,"targetDuration":27,"studyType":128,"phases":129,"briefSummary":131,"conditions":132,"keywords":135,"overallStatus":140,"whyStopped":27,"lastUpdateSubmitDate":141,"lastUpdatePostDateStruct":142,"startDateStruct":145,"completionDateStruct":147,"leadSponsor":149,"locationsCount":150},{"fullName":5,"class":6},"Beijing Tiantan Hospital","OTHER",[8,16],{"label":9,"type":10,"description":11,"interventionNames":12},"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 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. If a change in antibiotic selection is required during the period of combined treatment, the antibiotic administered via the intracalvariosseous route must remain consistent with that administered intravenously.",[13,14,15],"Procedure: Intracalvariosseous injection vancomycin\u002Ftigecycline\u002Fpolymyxin B","Drug: Intravenous injection vancomycin\u002Ftigecycline\u002Fpolymyxin B","Other: Conventional treatment",{"label":17,"type":18,"description":19,"interventionNames":20},"Intravenous injection","ACTIVE_COMPARATOR","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). The duration of intravenous therapy will be adjusted according to treatment response, including clinical symptoms, signs, and laboratory findings.",[14,15],[22,28,33],{"type":23,"name":24,"description":25,"armGroupLabels":26,"otherNames":27},"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).",[9],null,{"type":29,"name":30,"description":31,"armGroupLabels":32,"otherNames":27},"DRUG","Intravenous injection vancomycin\u002Ftigecycline\u002Fpolymyxin B","Intravenous infusion of polymyxin B (100 mg\u002Fday), tigecycline (100 mg\u002Fday), and vancomycin (2000 mg\u002Fday).",[9,17],{"type":6,"name":34,"description":35,"armGroupLabels":36,"otherNames":27},"Conventional treatment","Standard treatment and management according to related guidelines during the entire treatment period",[9,17],[38],{"name":39,"affiliation":5,"role":40},"Yilong Wang, PhD+MD","PRINCIPAL_INVESTIGATOR",[42],{"name":39,"role":43,"phone":44,"phoneExt":27,"email":45},"CONTACT","13569869755","yilong528@aliyun.com",[47,62,71,79,91,100],{"facility":5,"status":27,"city":48,"state":49,"zip":50,"country":51,"countryCode":52,"cosmosGeoPoint":53,"geoPoint":58,"contacts":59},"Beijing","Beijing Municipality","100071","China","CN",{"type":54,"coordinates":55},"Point",[56,57],116.39723,39.9075,{"lat":57,"lon":56},[60],{"name":61,"role":43,"phone":44,"phoneExt":27,"email":45},"Yilong Wang, MD+PhD",{"facility":63,"status":27,"city":64,"state":65,"zip":27,"country":51,"countryCode":52,"cosmosGeoPoint":66,"geoPoint":70,"contacts":27},"Kaifeng Central Hospital","Kaifeng","Henan",{"type":54,"coordinates":67},[68,69],114.30742,34.7986,{"lat":69,"lon":68},{"facility":72,"status":27,"city":73,"state":65,"zip":27,"country":51,"countryCode":52,"cosmosGeoPoint":74,"geoPoint":78,"contacts":27},"The First Affiliated Hospital of Xinxiang Medical University","Xinxiang",{"type":54,"coordinates":75},[76,77],113.80151,35.19033,{"lat":77,"lon":76},{"facility":80,"status":27,"city":81,"state":65,"zip":82,"country":51,"countryCode":52,"cosmosGeoPoint":83,"geoPoint":87,"contacts":88},"Henan Provincial People's Hospital","Zhengzhou","450000",{"type":54,"coordinates":84},[85,86],113.64861,34.75778,{"lat":86,"lon":85},[89],{"name":90,"role":43,"phone":27,"phoneExt":27,"email":27},"Guang Feng",{"facility":92,"status":27,"city":93,"state":94,"zip":27,"country":51,"countryCode":52,"cosmosGeoPoint":95,"geoPoint":99,"contacts":27},"Linyi City People Hospital","Linyi","Shandong",{"type":54,"coordinates":96},[97,98],118.34278,35.06306,{"lat":98,"lon":97},{"facility":101,"status":27,"city":102,"state":103,"zip":104,"country":51,"countryCode":52,"cosmosGeoPoint":105,"geoPoint":109,"contacts":27},"Tianjin Huanhu Hospital","Tianjin","Tianjin Municipality","300000",{"type":54,"coordinates":106},[107,108],117.17667,39.14222,{"lat":108,"lon":107},{"type":111,"investigatorFullName":112,"investigatorTitle":113,"investigatorAffiliation":5,"oldNameTitle":27,"oldOrganization":27},"SPONSOR_INVESTIGATOR","yilong Wang","Vice President of Beijing Tiantan Hospital","100631013","intracalvariosseous-plus-intravenous-antibiotics-for-moderate-to-severe-bacterial-meningitis-100631013",false,"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","FLAME","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\n  1. Meeting the diagnostic criteria for bacterial meningitis, i.e., meeting at least item i:\n\n     i. Abnormal body temperature (\\>38℃ or \\\u003C36℃), turbid or purulent Cerebrospinal fluid (CSF) , CSF leukocytosis (\\>500×10⁶\u002FL), CSF glucose\u002Fserum glucose concentration \\\u003C0.4, CSF protein concentration \\>50mg\u002FdL, meeting the clinical diagnosis; ii. In addition to item i, positive microbial tests or cultures of specimen smears, drainage tube heads, implants, and CSF (excluding contamination and colonization), meeting the etiological diagnosis;\n  2. GCS score ≤12 points or a decrease of 2 points from the previous score;\n  3. At least one of the following conditions is present: altered consciousness, seizures, brain parenchymal involvement, severe manifestations such as mechanical ventilation or circulatory support.\n* 3\\. After 48-72 hours of antibiotic treatment, if the investigator determines that the patient's condition shows no significant improvement or continues to worsen, or if at least one of the following conditions is present:\n\n  1. Symptoms and signs related to intracranial infection show no trend of relief or worsen;\n  2. CSF white blood cell count shows no trend of decrease, or increases after decreasing;\n  3. CSF protein concentration shows no trend of decrease, or increases after decreasing;\n  4. CSF\u002Fserum glucose concentration shows no trend of increase, or decreases after increasing;\n  5. CSF bacterial culture remains positive or becomes positive again after initially being negative.\n* 4\\. Based on the patient's condition, treatment with polymyxin B, tigecycline, or vancomycin may be necessary.\n* 5\\. Obtain informed consent.\n\nExclusion Criteria:\n\n* 1\\. History of allergy to polymyxin B, tigecycline, or vancomycin;\n* 2\\. Received intrathecal or intraventricular antibiotic treatment before randomization;\n* 3\\. Patients with severe pulmonary infection\u002Facute respiratory distress syndrome (PaO₂\u002FFiO₂ \\\u003C 150 mmHg, FiO₂ ≥ 0.6, PEEP ≥ 5 cmH₂O) or whose primary cause of mechanical ventilation is not determined to be intracranial infection;\n* 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\u002Fkg\u002Fmin) and lactate \\> 2 mmol\u002FL, or whose primary cause of critical illness is not determined to be intracranial infection;\n* 5\\. Patients with contraindications to transcranial administration, such as severe skull fracture, poor visualization of the skull diploic, or planned decompressive craniectomy, which may affect transcranial administration.\n* 6\\. Clinical signs of brain herniation, such as unilateral or bilateral pupillary dilation and fixation; or loss of other brainstem reflexes determined by the investigator to be caused by meningitis or brain herniation; or other uncontrollable signs of unstable vital signs;\n* 7\\. Bleeding tendency deemed unfavorable for the procedure by the investigator: abnormal coagulation function (e.g., platelet count \\\u003C50×10⁹\u002FL; prothrombin time \\[PT\\]\\>3s), patients with a previous diagnosis of hemophilia or other coagulation disorders;\n* 8\\. Patients with severe hepatic or renal insufficiency (where severe hepatic insufficiency is defined as alanine aminotransferase (ALT) value ≥3 times the upper limit of normal (ULN) or aspartate aminotransferase (AST) value ≥3 times the ULN; severe renal insufficiency is defined as serum creatinine (CRE) ≥1.5 times the ULN or glomerular filtration rate (eGFR) \\\u003C40 mL\u002Fmin\u002F1.73m²;\n* 9\\. Within the past 3 months, the patient has experienced an acute ST-segment elevation myocardial infarction and\u002For decompensated heart failure (meeting New York Heart Association \\[NYHA\\] functional class III or IV).\n* 10\\. Patients with severe or extremely severe anemia (hemoglobin \\\u003C 60 g\u002FL) at the time of randomization;\n* 11\\. Patients with active hepatitis B infection (positive hepatitis B surface antigen and\u002For positive serum HBV DNA or serum HBV DNA \\> 2 × 10⁸ IU\u002Fml);\n* 12\\. Patients with positive hepatitis C virus antibody or a history of positive testing;\n* 13\\. Patients with positive HIV test or a history of positive testing;\n* 14\\. Pregnant, lactating, or potentially pregnant patients, or patients planning to become pregnant;\n* 15\\. Patients currently participating in other interventional trials or who have used other investigational drugs within one month or five drug half-lives;\n* 16\\. Patients deemed unsuitable for participation in this study by the investigator.","ALL","18 Years","75 Years",{"count":126,"type":127},86,"ESTIMATED","INTERVENTIONAL",[130],"NA","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.",[133,134],"Blood-Brain Barrier","Bacterial Meningitis",[133,136,137,138,139],"Bacterial meningitis","Prognosis","Intracalvariosseous","Antibiotic","NOT_YET_RECRUITING","2026-03-21",{"date":143,"type":144},"2026-03-27","ACTUAL",{"date":146,"type":127},"2026-04-01",{"date":148,"type":127},"2027-07-01",{"name":112,"class":6},6]