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O estudo clínico NCT07495150 (FLAME) para Blood-Brain Barrier, Meningite bacteriana está ainda não recrutando. Consulte a visualização em cartões do Radar de Estudos Clínicos e as ferramentas de descoberta de IA para ver todos os detalhes. Ou pergunte qualquer coisa aqui. | ||
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Intracalvariosseous Plus Intravenous Antibiotics for Moderate-to-Severe Bacterial Meningitis (FLAME) 86
Os detalhes do estudo clínico estão disponíveis principalmente em inglês. No entanto, a IA Trial Radar pode ajudar! Basta clicar em 'Explicar o estudo' para visualizar e discutir as informações do estudo no idioma selecionado.
O estudo clínico NCT07495150 (FLAME) é um estudo intervencionista para Blood-Brain Barrier, Meningite bacteriana. Seu status atual é: ainda não recrutando. O recrutamento está programado para iniciar em 1 de abril de 2026, com o objetivo de incluir 86 participantes. Coordenado por yilong Wang e deve ser concluído em 1 de julho de 2027. Essas informações foram atualizadas no ClinicalTrials.gov em 27 de março de 2026.
Resumo
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 bacter...Mostrar mais
Descrição detalhada
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 susta...Mostrar mais
Título oficial
Efficacy and Safety of Intracalvariosseous Combined With Intravenous Injection of Antibiotics in Moderate-to-Severe Bacterial Meningitis
Condições médicas
Blood-Brain BarrierMeningite bacterianaOutros IDs do estudo
- FLAME
- CX25YZ07
Número NCT
Data de início (real)
2026-04-01
Última atualização postada
2026-03-27
Data de conclusão (estimada)
2027-07-01
Inscrição (estimada)
86
Tipo de estudo
Intervencionista
FASE
N/A
Status
Ainda não recrutando
Palavras-chave
Blood-Brain Barrier
Bacterial meningitis
Prognosis
Intracalvariosseous
Antibiotic
Bacterial meningitis
Prognosis
Intracalvariosseous
Antibiotic
Propósito principal
Tratamento
Alocação do design
Randomizado
Modelo de intervenção
Paralelo
Cegamento (Mascaramento)
Cego simples
Braços / Intervenções
| Grupo de participantes/Braço | Intervenção/Tratamento |
|---|---|
ExperimentalIntracalvariosseous injection + Intravenous injection 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 i...Mostrar mais | 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). Intravenous injection vancomycin/tigecycline/polymyxin B Intravenous infusion of polymyxin B (100 mg/day), tigecycline (100 mg/day), and vancomycin (2000 mg/day). Tratamento convencional Standard treatment and management according to related guidelines during the entire treatment period |
Comparador ativoIntravenous injection 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. | Intravenous injection vancomycin/tigecycline/polymyxin B Intravenous infusion of polymyxin B (100 mg/day), tigecycline (100 mg/day), and vancomycin (2000 mg/day). Tratamento convencional Standard treatment and management according to related guidelines during the entire treatment period |
Desfecho primário
Desfecho secundário
| Medida de desfecho | Descrição da medida | Prazo |
|---|---|---|
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. | 8,10 and 14 days after randomization |
| Medida de desfecho | Descrição da medida | Prazo |
|---|---|---|
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. | 8,10 and 14 days after randomization |
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. | 8,10 and 14 days after randomization |
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 | 48-72 hours after randomization, Days 5, 8, 10, and 14 after randomization |
Cerebrospinal fluid protein concentration at 48-72 hours and Days 5, 8, 10, and 14 after randomization | Cerebrospinal fluid protein concentration | 48-72 hours after randomization, Days 5, 8, 10, and 14 after randomization |
Cerebrospinal fluid-to-serum glucose concentration ratio at 48-72 hours and Days 5, 8, 10, and 14 after randomization | Cerebrospinal fluid-to-serum glucose concentration ratio | 48-72 hours after randomization, Days 5, 8, 10, and 14 after randomization |
Cerebrospinal fluid bacteriological culture results at 48-72 hours and Days 5, 8, 10, and 14 after randomization | Cerebrospinal fluid bacteriological culture results | 48-72 hours after randomization, Days 5, 8, 10, and 14 after randomization |
Glasgow Coma Scale (GCS) scores at 48-72 hours and Days 5, 8, 10, and 14 after randomization | Glasgow Coma Scale (GCS) is a neurological scale that assesses level of consciousness using 3 components: eye opening, verbal response, and motor response. The total score ranges from 3 to 15, with higher scores indicating a better neurological outcome / level of consciousness and lower scores indicating a worse outcome / deeper impairment of consciousness. | 48-72 hours after randomization, Days 5, 8, 10, and 14 after randomization |
Proportion of participants who require conversion to intrathecal or intraventricular antibiotic therapy during the 48-72 hour period after randomization | This proportion is defined as the number of participants who are evaluated during the 48-72-hour period after randomization and are judged to have an unsatisfactory treatment response requiring conversion to intrathecal or intraventricular antibiotic therapy, divided by the total number of participants in the corresponding treatment group. An unsatisfactory treatment response is defined as the absence of an improving trend, compared with baseline, in cerebrospinal fluid white blood cell count, protein concentration, and cerebrospinal fluid-to-serum glucose concentration ratio. | During the 48-72 hour period after randomization |
All-cause mortality from baseline to 14-day | All-cause mortality | Baseline to Day 14 |
Mortality due to meningitis from baseline to 14-day | 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. | Baseline to Day 14 |
Assistente de participação
Critérios de elegibilidade
Idades elegíveis
Adulto, Idoso
Idade mínima
18 Years
Sexos elegíveis
Todos
1. Age 18-75 years, gender not limited;
2. Meeting the diagnostic criteria for moderate to severe bacterial meningitis:
Meeting the diagnostic criteria for bacterial meningitis, i.e., meeting at least item i:
i. Abnormal body temperature (>38℃ or <36℃), turbid or purulent Cerebrospinal fluid (CSF) , CSF leukocytosis (>500×10⁶/L), CSF glucose/serum glucose concentration <0.4, CSF protein concentration >50mg/dL, 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;
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.
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:
- Symptoms and signs related to intracranial infection show no trend of relief or worsen;
- CSF white blood cell count shows no trend of decrease, or increases after decreasing;
- CSF protein concentration shows no trend of decrease, or increases after decreasing;
- CSF/serum glucose concentration shows no trend of increase, or decreases after increasing;
- CSF bacterial culture remains positive or becomes positive again after initially being negative.
4. Based on the patient's condition, treatment with polymyxin B, tigecycline, or vancomycin may be necessary.
5. Obtain informed consent.
- 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;
- 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.
- 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;
- 7. Bleeding tendency deemed unfavorable for the procedure by the investigator: abnormal coagulation function (e.g., platelet count <50×10⁹/L; prothrombin time \[PT\]>3s), patients with a previous diagnosis of hemophilia or other coagulation disorders;
- 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) <40 mL/min/1.73m²;
- 9. Within the past 3 months, the patient has experienced an acute ST-segment elevation myocardial infarction and/or decompensated heart failure (meeting New York Heart Association \[NYHA\] functional class III or IV).
- 10. Patients with severe or extremely severe anemia (hemoglobin < 60 g/L) at the time of randomization;
- 11. Patients with active hepatitis B infection (positive hepatitis B surface antigen and/or positive serum HBV DNA or serum HBV DNA > 2 × 10⁸ IU/ml);
- 12. Patients with positive hepatitis C virus antibody or a history of positive testing;
- 13. Patients with positive HIV test or a history of positive testing;
- 14. Pregnant, lactating, or potentially pregnant patients, or patients planning to become pregnant;
- 15. Patients currently participating in other interventional trials or who have used other investigational drugs within one month or five drug half-lives;
- 16. Patients deemed unsuitable for participation in this study by the investigator.
yilong WangResponsável pelo estudo
yilong Wang, Patrocinador-Investigador, Vice President of Beijing Tiantan Hospital
Contato central do estudo
Contato: Yilong Wang, PhD+MD, 13569869755, [email protected]
6 Locais do estudo em 1 países
Beijing Municipality
Beijing Tiantan Hospital, Beijing, Beijing Municipality, 100071, China
Yilong Wang, MD+PhD, Contato, 13569869755, [email protected]
Henan
Kaifeng Central Hospital, Kaifeng, Henan, China
The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China
Henan Provincial People's Hospital, Zhengzhou, Henan, 450000, China
Guang Feng, Contato
Shandong
Linyi City People Hospital, Linyi, Shandong, China
Tianjin Municipality
Tianjin Huanhu Hospital, Tianjin, Tianjin Municipality, 300000, China