Prospective observational study on the pharmacokinetic properties of the Irrua ribavirin regimen used in routine clinical practice in patients with Lassa fever in Nigeria

Abstract

IntroductionLassa 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.Methods and analysisThis 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.Ethics and disseminationThe 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.Registration detailsISRCTN11104750