Factors on Therapeutic Drug Monitoring and Safety of Voriconazole in Critically Ill Elderly Patients: A Prospective Observational Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 550
- 试验地点
- 1
- 主要终点
- CYP2C19 Genotyping
研究概览
简要总结
This was a prospective clinical study that all voriconazole-treated adult Chinese patients with invasive pulmonary infection admitted to Zhengzhou Central Hospital affiliated to Zhengzhou University from July 2018 to June 2023. The initial voriconazole serum trough concentration, Correlation of various factors, and risk prediction factors for voriconazole serum trough concentration and hepatotoxicity were compared between elderly and non-elderly patients.
详细描述
A prospective observational study was conducted from July 2018 to June 2023 in Zhengzhou Central Hospital Affiliated to Zhengzhou University. This study was carried out in accordance with the following criteria: (1) patients who met the criteria for diagnosis of IFI, (2) age ≥ 18 years, (3) The duration of VCZ treatment course ≥ 7 days.
Patients were excluded who fulfilled any of the following criteria: (1) Patients who allergic to VCZ, (2) use other anti-fungal drugs during the use of VCZ, (3) do not qualify for blood sampling monitored by blood concentration, (4) pregnant or lactating women, (5) patients who haven't completely and accurately efficacy and safety data, (6) patients who are treated with a combination of liver enzyme inducers and inhibitors (carbamazepine, phenobarbital, phenytoin, cimetidine, rifampin, rifapentine, rifabutin, and so on),(7) patients who are treated with a combination of Paxlovid or Azvudine.
Grouping: Patients were divided into the elderly group (group A, ≥ 60 years) and the non-elderly group (group B, < 60 years) according to ages. All the recruited patients were treated with voriconazole. Voriconazole was intravenously administered 2 times at the loading dose of 6 mg/Kg or orally administered 2 times at the loading dose of 400mg at 12h intervals, followed by a maintenance dose of 4 mg/Kg or 200 mg at 12 h intervals.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 98 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •patients who met the criteria for diagnosis of IFI
- •age ≥ 18 years
- •The duration of VCZ treatment course ≥ 7 days.
排除标准
- •Patients who allergic to VCZ
- •use other anti-fungal drugs during the use of VCZ
- •do not qualify for blood sampling monitored by blood concentration
- •pregnant or lactating women
- •patients who haven't completely and accurately efficacy and safety data
- •patients who are treated with a combination of liver enzyme inducers and inhibitors(carbamazepine, phenobarbital, phenytoin, cimetidine, rifampin, rifapentine, rifabutin, and so on)
- •patients who are treated with a combination of Paxlovid or Azvudine.
结局指标
主要结局
CYP2C19 Genotyping
时间窗: Unlimited blood drawing time.
CYP2C19 genotype was determined from peripheral blood, which was extracted and stored in an EDTA anticoagulant tube. Real-time fluorescence quantitative PCR (ThermoFisher Applied Biosystems 7500 fast PCR) was performed using a Human CYP2C19 gene detection kit (PCR-fluorescence probe method, Wuhan YZY Medical Science and Technology Co., Ltd, China) following the manufacturer's instructions. Genomic DNA was isolated from whole blood using QIAamp DNA blood kits (Qiagen, Hilden, Germany). According to nomenclature by the Clinical Pharmacogenetics Implementation Consortium (CPIC®), the CYP2C19 genotype was classified as ultrarapid metabolizer (\*17/\*17), rapid metabolizer (\*1/\*17), normal metabolizer (\*1/\*1), intermediate metabolizer (\*1/\*2, \*1/\*3, \*2/\*17, \*3/\*17), or poor metabolizer (\*2/\*2, \*2/\*3, \*3/\*3).
Analysis of factors affecting voriconazole serum trough concentration
时间窗: From July 2018 to June 2023
A multiple linear stepwise regression analysis was performed by using voriconazole serum trough concentration (Y) as the dependent variable, and sex (x1), age (x2), body weight (x3), VCZ route of administration (x4), CYP2C19 phenotype (x5), the average daily dose (x6), PPIs (x7), methylprednisolone (x8), CRP (x9) , PCT (x10), IL-6 (x11), Albumin (x12), ALP (x13), and TBIL (x14) as independent variables. Linear regression analysis reveals the regression equation and independent risk factors affecting voriconazole serum trough concentration.
Serum voriconazole trough concentrations
时间窗: 0.5 hour before voriconazole administration on the Third or sixth day.
If all patients were administrated by loading dose, voriconazole trough samples were taken immediately 30 minutes before voriconazole administration on the Third day. If all patients were not administrated by loading dose, voriconazole trough samples were taken immediately 30 minutes before voriconazole administration on the sixth day. Blood samples for 2-3 mL were collected in blood-collection tubes without any additives and centrifuged at 3500 rpm for 10min. Serum trough concentrations were determined by a high-performance liquid chromatography method as previously described. A initial steady-state trough concentration blood sample was obtained before dose adjustment for all patients. Each patient received at least one steady-state blood sample. The detections were completed in Translational Medicine Center of Zhengzhou Central Hospital affiliated to Zhengzhou University.
The difference of average voriconazole serum trough concentration between group A and group B
时间窗: From July 2018 to June 2023
The differences were counted between group A and group B by measuring each patient's voriconazole serum trough concentration.
次要结局
- Gamma-glutamyl transferase(GGT)(Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy)
- Total bilirubin (TBIL)(Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy)
- C-reaction protein (CRP)(Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy)
- Aspartatrtransaminase (AST)(Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy)
- procalcitonin(PCT)(Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy)
- Alanine aminotransferase (ALT)(Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy)
- Alkaline phosphatase (ALP)(Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy)
- interleukin- 6(IL-6)(before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy)
研究者
LIjuan Zhou
Principal Investigator
People's Hospital of Zhengzhou University