Cardiovascular Function and Ribavirin Pharmacokinetics and Pharmacodynamics in Patients With Lassa Fever

Terminated

• Conditions: Lassa Fever
• Interventions: Drug: Ribavirin

• Registration Number: NCT03889106
• Lead Sponsor: University of Oxford

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2019-03
• Study Start: 2019-03-01
• Study First Submitted: 2019-03-13
• Study First Submitted QC: 2019-03-21
• Study First Posted: 2019-03-26
• Primary Completion: 2020-10-01
• Study Completion: 2020-10-01
• Last Update Submitted: 2022-07-01
• Last Update Posted: 2022-07-06

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

• Positive antigen or PCR test for Lassa fever
• Aged 10 years or above

Exclusion Criteria

• Patients for end of life care only

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Lassa fever	Ribavirin	-

Primary Outcome Measures

Name	Time	Method
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
Cardiovascular function - primary	Up to 28 days during hospitalisation	Death during hospitalization

Secondary Outcome Measures

Name	Time	Method
Cardiovascular function - secondary	Up to 28 days during hospitalisation	• Respiratory distress (respiratory distress is defined as a respiratory rate \> 24 (age specific in children) AND oxygen saturations \< 94% OR use of supplemental oxygen)
Ribavirin PK - secondary	Up to 15 days during hospitalisation	• Half life
Ribavirin PD (mechanism of action)	Up to 15 days during hospitalisation	• Change in systemic nitric oxide concentrations from baseline to day 3/5

Trial Locations

Locations (1)

Kenema Government Hospital; 🇸🇱 Kenema, Sierra Leone