Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Nigeria.
Department of Medicine, Irrua Specialist Teaching Hospital, Irrua, Nigeria.
BMJ Open. 2020 Apr 16;10(4):e036936. doi: 10.1136/bmjopen-2020-036936.
Lassa fever (LF) is a severe and often fatal systemic disease in humans and affects a large number of countries in West Africa. Treatment options are limited to supportive care and the broad-spectrum antiviral agent ribavirin. However, evidence for ribavirin efficacy in patients with LF is poor and pharmacokinetic (PK) data are not available.Irrua Specialist Teaching Hospital (ISTH) developed an intravenous ribavirin regimen different to the WHO recommendation. Apart from a lower total daily dose the drug is usually administered once per day which reduces the exposure of personnel to patients with LF. The aim of this study is to characterise the PK of the Irrua ribavirin regimen.
This prospective, observational clinical study will assess PK properties of the Irrua ribavirin regimen on routinely ribavirin-treated patients with LF at ISTH, a referral hospital serving 19 local governmental areas in a LF endemic zone in Nigeria. Participants will be adults with PCR-confirmed LF. The primary objective is to describe classical PK parameters for ribavirin (maximum plasma drug concentration, time to maximum plasma drug concentration, area under the plasma drug concentration vs time curve, half-life time T1/2, volume of distribution). Blood samples will be collected at 0.5, 1, 3, 5, 8, 12 and 24 hours after doses on day 1, day 4 and day 10 of ribavirin treatment. Ribavirin plasma concentrations will be determined using liquid chromatography coupled to tandem mass spectrometry.
The study will be conducted in compliance with the protocol, the Declaration of Helsinki, Good Clinical Practice (GCP) and the Nigerian National Code for Health Research Ethics. The protocol has received approval by the Health Research Ethics Committee of ISTH. Results will be made available to LF survivors, their caregivers, the funders, LF research society and other researchers.
ISRCTN11104750.
拉沙热（LF）是一种严重且常致命的人类系统性疾病，影响西非的多个国家。治疗选择仅限于支持性护理和广谱抗病毒药物利巴韦林。然而，利巴韦林治疗 LF 患者的疗效证据不足，且药代动力学（PK）数据不可用。Irrua 专科教学医院（ISTH）开发了一种不同于世界卫生组织（WHO）建议的静脉内利巴韦林方案。除了总日剂量较低外，该药物通常每天给药一次，从而降低了医务人员接触 LF 患者的暴露风险。本研究旨在描述 Irrua 利巴韦林方案的 PK 特征。
这项前瞻性、观察性临床研究将评估在 ISTH 接受利巴韦林常规治疗的 LF 患者的 Irrua 利巴韦林方案的 PK 特性，ISTH 是一家在尼日利亚 LF 流行区为 19 个地方政府区提供服务的转诊医院。参与者将是经 PCR 确诊的 LF 成人。主要目的是描述利巴韦林的经典 PK 参数（最大血浆药物浓度、达峰时间、血浆药物浓度-时间曲线下面积、半衰期 T1/2、分布容积）。在利巴韦林治疗第 1 天、第 4 天和第 10 天，分别在给药后 0.5、1、3、5、8、12 和 24 小时采集血样。将使用液相色谱-串联质谱法测定利巴韦林的血浆浓度。
该研究将按照方案、《赫尔辛基宣言》、良好临床实践（GCP）和尼日利亚国家卫生研究伦理规范进行。该方案已获得 ISTH 卫生研究伦理委员会的批准。研究结果将提供给 LF 幸存者、他们的照顾者、资助者、LF 研究协会和其他研究人员。
ISRCTN84025736。
