Hydroxychloroquine for the Treatment of SARS-CoV2 (COVID 19) in the Critically Ill Patient: Pharmacokinetic Study. (CHLORO-VID)
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- residual plasma concentration
研究概览
简要总结
This study is a prospective, observational, open, monocentric multisite, pharmacokinetic study of hydroxychloroquine in critically ill patients. The aim of this study is to assess the pharmacokinetic behavior of hydroxychloroquine in COVID-19 critically ill patients treated with crushed hydroxychloroquine tablets (administered enterally using a nasogastric tube).
详细描述
Based on the in vitro activity against SARS-CoV-2 and preliminary clinical data, hydroxychloroquine is currently used in the management of COVID-19 patients. In the meantime, the efficacy as well as the dosage of hydroxychloroquine is highly debated. Because of the severity of COVID-19 and the pharmacokinetics of hydroxychloroquine in systemic lupus erythematosus patients, a loading dose was rapidly included in the new hospital regimens to optimize drug distribution in tissues and more precisely in the lungs. Due to the lack of information on the plasma/blood concentrations required to induce a virological/clinical effect, plasma/blood concentration is monitored in many European countries for patients whether or not they are included in clinical research protocols. This problem of relationship between efficacy and exposure is important in the critically ill patient because both the bioavailability and the variability of the pharmacokinetic parameters are potentially responsible for variations in concentrations.
This study is a prospective, observational, open, multisite, pharmacokinetics study of hydroxychloroquine in critically ill patients. There is no supplemental intervention or additional samples compared to the standard care of these patients in our teaching hospital. The total duration of the study is that of the duration of hospitalization in intensive care. The duration of the pharmacokinetic study is 9 days, starting on D1 of the treatment with hydroxychloroquine, and ending with the last recommended residual plasma control. The total duration of treatment with hydroxychloroquine is 10 days, as recommended by the High Council of Public Health in its opinion of March 23, 2020.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient ≥ 18 years old,
- •Hospitalized in intensive care, intubated and ventilated
- •With COVID-19 pneumonia confirmed by Rt-PCR,
- •Having as specific treatment hydroxychloroquine, whatever the dosage regimen
- •Having had the monitoring of the residual concentrations carried out by the Pharmacokinetics and Toxicology Laboratory of the Federative Institute of Biology of the Toulouse University Hospital the clinical Pharmacology and Toxicology laboratory of the Toulouse University Hospital
- •Person affiliated to a social security scheme or equivalent
排除标准
- •Minor patients
- •Patients refusing to participate in the study
- •Person participating in another research including an exclusion period still in progress.
- •Contraindications to hydroxychloroquine: pre-existing retinopathy, known hypersensitivity to 4-aminoquinolines, hemolytic anemia, porphyria, G6PD deficiency, myasthenia gravis, association with citalopram, escitalopram, hydroxyzine, domperidone and piperaquine
- •Patients undergoing treatment with medicines known to prolong the QT interval or likely to induce a cardiac arrhythmia such as for example anti-arrhythmics of class IA and III, tricyclic antidepressants and certain anti-infectives (in particular antibiotics of the family of macrolides and fluoroquinolones as well as trimethoprim-sulfamethoxazole).
- •Pregnant or breastfeeding women
结局指标
主要结局
residual plasma concentration
时间窗: Day 9
residual plasma concentration measured before re-administration of the treatment
次要结局
- The number of days without artificial ventilation(Day 28)
- The length of hospital stay in intensive care(Day 28)
- Survival(Day 28)
- Viral replication in the control bronchoalveolar lavage fluid on Day 7(Day 7)
- Viral replication in the control bronchoalveolar lavage fluid on Day 14(Day 14)