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

NCT03889106 | Terminated

• 1 other identifier: 38-18
• Study Type: observational
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Lassa Fever

Outcome Measures

Primary Outcomes (3)

• Cardiovascular function - primary

  Death during hospitalization

  Up to 28 days during hospitalisation

• Ribavirin PK - primary

  Proportion of patients with ribavirin CMIN above the IC90 at all measured CMIN during therapy

  Up to 15 days during hospitalisation

• Ribavirin PD (mechanism of action) - primary

  • Change in Lassa virus viral load (copies/ml) from baseline to day 3/5

  Up to 15 days during hospitalisation

Secondary Outcomes (14)

• Cardiovascular function - secondary

  Up to 28 days during hospitalisation

• Cardiovascular function - secondary

  Up to 28 days during hospitalisation

• Cardiovascular function - secondary

  Up to 28 days during hospitalisation

• Ribavirin PK - secondary

  Up to 15 days during hospitalisation

• Ribavirin PK - secondary

  Up to 15 days during hospitalisation

Study Arms (1)

Lassa fever

Drug: Ribavirin

Interventions

Ribavirin DRUG

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.

Lassa fever

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients admitted to KGH with a positive antigen or PCR test for Lassa virus.

You may qualify if:

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

You may not qualify if:

• Patients for end of life care only

Sponsors & Collaborators

• University of Oxford: lead
• National Institute for Health Research, United Kingdom: collaborator
• Kenema Government Hospital: collaborator
• London School of Hygiene and Tropical Medicine: collaborator
• Public Health England: collaborator

Study Sites (1)

Kenema Government Hospital

Kenema, Sierra Leone

Location

MeSH Terms

Conditions

Lassa Fever

Interventions

Ribavirin

Condition Hierarchy (Ancestors)

Arenaviridae Infections; RNA Virus Infections; Virus Diseases; Infections; Hemorrhagic Fevers, Viral

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Alex Salam, MD

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2019
• First Posted: March 26, 2019
• Study Start: March 1, 2019
• Primary Completion: October 1, 2020
• Study Completion: October 1, 2020
• Last Updated: July 6, 2022

Record last verified: 2019-03

Locations

SI (1)