Tolérance du Linézolide Pendant le Régime BPaL Avec Personnalisation de la Posologie Basée Sur la Surveillance Thérapeutique Des Médicaments (TDM) au Cours du Traitement de la Tuberculose Multirésistante
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Rate of linezolid related side effects.
研究概览
简要总结
Multidrug-resistant tuberculosis (MDR-TB) poses a significant challenge to global public health.
Globally, the World Health Organization (WHO) estimates the number at 400,000 patients with MDR-TB for 2023. Only 44% were diagnosed and put on treatment, the therapeutic success rate of the 2021 cohort is only 68%.
In Guinea, the number of patients with MDR-TB is estimated at 450, and the treatment success rate is 74% for the 2021 cohort, primarily with the 9-months short oral regimen.
Since 2022, the WHO has recommended the use of the 6-month short course of BPaL/BPaL-M for national tuberculosis control programs and Guinea began implementing this new regime within the programmatic framework starting in January 2025.
Linezolid, a key component of new therapeutic regimens such as BPaL/BPaL-M, shows high bactericidal activity, although it is associated with serious adverse effects in a high percentage of patients, including myelosuppression, neuropathy and, in some cases, fatal lactic acidosis. In particular, peripheral neuropathy, an adverse event often irreversible that may lead to linezolid and the BPaL/BPaL-M regimen discontinuation, is reported in approximately 24% of patients receiving linezolid at 600 mg.
A linezolid blood trough level of above 2 mg/l is associated with side effects, but its pharmacokinetics varies considerably between individuals and over time.
There is little data on the role of therapeutic drug monitoring (TDM) in guiding its administration, some studies showing how the standard dose of 600 mg could exceed the toxicity target and the reduced dose of 300 mg might not achieve the target efficacy.
The main objective of this study is to determine the role of TDM in the optimization of linezolid dosage in TB-MDR patients treated with the BPaL/BPaL-M regimen.
The specific objectives aim to evaluate:
- the variation in the occurrence of adverse events between patients who undergo a modification of the linezolid dose based on the TDM and patients taking linezolid standard dose
- the treatment outcome in patients who undergo a modification of the linezolid dose based on TDM and patients taking linezolid standard dose
- variations in the distribution of TDM throughout treatment in order to identify potential common trends.
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
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. Confirmed diagnosis of MDR-TB
- •2. Linezolid prescribed as part of the BPaL/BPaL-M regimen
- •3. Age 15 years or older
- •4. Informed consent obtained from the participant or assent from the parent/legal guardian for participants under 18 years of age.
排除标准
- •1. Pregnancy or breastfeeding
- •2. Severe liver or kidney failure
- •3. Known hypersensitivity to linezolid
- •4. Concomitant use of medications with drug interactions potential with linezolid
研究组 & 干预措施
Group A: linezolid 600 mg standard dose. Only TDM monitoring
Linezolid will be administered at the recommended dose of 600 mg. The linezolid level will be measured for each patient once a week during the first month (4 blood samples), then once a month for the following 5 months (5 blood samples) to complete the 6-month regimen (at least 9 blood samples for each patient). One additional sample will be taken if linezolid-related side effects appear. No changes to the linezolid dosage will be made except as directed in accordance with the national guidelines for the management of MDR-TB.
Group B: linezolid dose personalization based on TDM
Linezolid will be initially administered at the recommended dose of 600 mg. The linezolid level will be measured for each patient once a week during the first month (4 blood samples), then once a month for the following 5 months (5 blood samples) to complete the 6-month regimen (at least 9 blood samples for each patient). Additional samples will be taken if linezolid-related side effects appear or if the trough linezolid concentration in the blood does not reach the reference range of 0.6-2 mg/l. The dosage of linezolid will be modified according to the TDM
干预措施: Linezolid dose personalization based on TDM (Drug)
结局指标
主要结局
Rate of linezolid related side effects.
时间窗: From enrollment to the end of treatment at 6 months
The primary objective is to evaluate the variation in the rate of occurrence of adverse events between patients who undergo a modification of the linezolid dose based on the TDM and patients taking linezolid standard dose. We hypothesize that patients who under go linezolid dose personalization based on TDM will maintain linezolid blood levels within the therapeutic range (0.6-2 mg/l). This could result in a different rate in linezolid related side effects between the two groups
次要结局
- Feasibility of linezolid dosage personalization based on TDM in low resources setting(From enrollment to the end of treatment at 6 months)
- Treatment outcome(From the enrollment to the end of the treatment at 6 months)
- Linezolid TDM trends(From enrollment to the end of treatment at 6 months)
研究者
Marco Schiuma
Medical Doctor, Infectious Diseases Specialist
ASST Fatebenefratelli Sacco