Lassa Fever
Conditions
Brief summary
Lassa fever carries a treated mortality in hospitalized patients of up to 50%. Lassa fever is often described as being characterized by vascular leak and shock in the terminal phase, but, whilst animal data supports this, there are limited data in humans. Therefore, an aim of this study therefore is to characterize cardiovascular function in patients with Lassa fever, with the ultimate goal of informing future trials of supportive or therapeutic strategies. Ribavirin is the current standard of care. However, the efficacy of ribavirin has not been established in a randomised controlled trial (RCT). There is very limited pharmacokinetic (PK) data on ribavirin in patients with Lassa fever and the optimal dose of ribavirin for an RCT is unknown. Furthermore, there are various hypothesized mechanisms of action of ribavirin, none of which have been investigated in humans with Lassa fever. Further aims of this study therefore are to characterize the PK of ribavirin in Lassa fever, and identify any associations between ribavirin PK parameters, viral load and markers of immune/inflammatory status.
Interventions
DRUGRibavirin
Standard of care: Intravenous administration of ribavirin at currently recommended dosages. Loading dose of 30 mg/kg (maximum 2 g), followed by 15 mg/kg (maximum 1 g) intravenously QDS for four days, followed by 7.5 mg/kg intravenously (maximum 500 mg) TDS for six days.
Sponsors
National Institute for Health Research, United Kingdom
Kenema Government Hospital
London School of Hygiene and Tropical Medicine
Public Health England
University of Oxford
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
10 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Positive antigen or PCR test for Lassa fever * Aged 10 years or above
Exclusion criteria
* Patients for end of life care only
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cardiovascular function - primary | Up to 28 days during hospitalisation | Death during hospitalization |
| Ribavirin PK - primary | Up to 15 days during hospitalisation | Proportion of patients with ribavirin CMIN above the IC90 at all measured CMIN during therapy |
| Ribavirin PD (mechanism of action) - primary | Up to 15 days during hospitalisation | • Change in Lassa virus viral load (copies/ml) from baseline to day 3/5 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cardiovascular function - secondary | Up to 28 days during hospitalisation | • Shock (shock is defined as a systolic BP \< 90mmgHg \[age specific in children\] OR a MAP \< 65mmgHg AND a lactate \> 2 mEq/L) |
| Ribavirin PK - secondary | Up to 15 days during hospitalisation | • Proportion of patients with ribavirin CMIN above the IC50 at all measured CMIN during therapy |
| Ribavirin PD (mechanism of action) | Up to 15 days during hospitalisation | • Change in ISG expression from baseline to day 3/5 |
Countries
Sierra Leone
Outcome results
None listed