Optimizing Linezolid Dosing in Patients With Advanced Renal Impairment: a Therapeutic Drug Monitoring-based Evaluation
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 50
- 主要终点
- Therapeutic range trough targeting
研究概览
简要总结
The goal of this clinical trial is to adjust the Linezolid dose according to its blood level in adults with kidney diseases. It will also learn about the safety of linezolid. The main questions it aims to answer are:
- How often does linezolid require level monitoring?
- How often does linezolid require dose adjustment?
- What medical benefits do participants have when linezolid level monitoring is applied? Researchers will compare two dose reduction regimens when they have evidence of overexposure to determine which regimen is more effective in preventing thrombocytopenia (Platelet drop).
Participants will:
- Withdrew linezolid level every 2 to 4 days of the antibiotic course.
- Visit the clinic twice for checkups and tests.
详细描述
Linezolid is a crucial antibiotic prescribed for the treatment of various infectious diseases such as pneumonia, skin infections, and catheter-related bloodstream infections. Linezolid covers gram-positive bacteria, including Methicillin-resistant Staphylococcus Auris (MRSA) and Vancomycin-resistant Staphylococcus Auris (VRSA).
Recently, Linezolid usage has become favorable for chronic kidney disease (CKD) patients to preserve the remaining residual renal function by avoiding nephrotoxic antibiotics such as vancomycin and aminoglycosides. However, linezolid-induced thrombocytopenia hinders linezolid use in the CKD population due to accumulation and overexposure. Recent literature suggested implementing a therapeutic drug monitoring (TDM) approach to modify the dose regimen and minimize linezolid toxicity.
The obstacle faced was the lack of clear TDM-based linezolid modification guidelines for CKD patients. To overcome this issue, we conducted a pilot study involving 15 patients (7 ESRD, 5 CKD, and 3 AKI on top of CKD). Patients with evidence of toxic levels (8 patients) underwent dose adjustment from 600mg every 12 hours to 300mg every 12 hours.
Dose reduction by 50% with no change in dose interval resulted in a decrease in supratherapeutic trough levels. However, these levels, while lower, did not consistently reach the predefined target therapeutic range (2-8 mg/dl).
The recent approach we are investigating now is to both lower the dose and elongate the interval.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Advanced renal impairment, Hemodialysis patients
排除标准
- •Pregnancy, Lactating females, Advanced Liver impairment, Cases using antidepressants or antipsychotics, Cases suffering from Hematological blood diseases, and/or chronic Immune thrombocytopenia.
研究组 & 干预措施
Group 1
Linezolid level within therapeutic range
干预措施: Linezolid (IV and PO) (Drug)
Group 2
Above the therapeutic range and within the toxicity range
干预措施: Linezolid (IV and PO) (Drug)
Group 3
Above the therapeutic range and within the toxicity range
干预措施: Linezolid (IV and PO) (Drug)
结局指标
主要结局
Therapeutic range trough targeting
时间窗: From enrollment to the end of antibiotic treatment duration (typically 10 to 14 days)
Linezolid Therapeutic Range Trough Targeting - The proportion of patients whose steady-state linezolid trough concentrations fall within the predefined therapeutic range (e.g., 2-8 mg/L) during treatment as a result of level monitoring and dose correction. This range is the established range for antimicrobial efficacy while minimizing the risk of toxicity, particularly hematological adverse effects. Concentrations will be measured using validated analytical method using HPLC device, and results will be compared to target thresholds to evaluate dosing adequacy.
次要结局
- Incidence of New-Onset Thrombocytopenia(From enrollment to the end of antibiotic treatment duration (typically 10 to 14 days))
- Correlation Between Linezolid Trough Concentrations and Thrombocytopenia(From enrollment to the end of antibiotic treatment (typically 10-14 days).)