Clinical trial NCT04285034: Cardiovascular Function and Ribavirin PK/PD in Lassa Fever in Lassa Fever
Official title: Cardiovascular Function and Ribavirin Pharmacokinetics and Pharmacodynamics in Lassa Fever Patients in Nigeria: a Prospective Observational Cohort Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Lassa Fever
Lead sponsor: University of Oxford
Sponsor class: OTHER
First posted: 2020-02-26
Enrollment: 158
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients admitted to Lassa fever treatment centres with a diagnosis of suspected or RT-PCR confirmed Lassa fever.

Brief summary: Arenaviruses are included in the World Health Organisation R\&D Blueprint list of high priority pathogens, since this virus group includes several epidemic-prone highly pathogenic viruses for which there are inadequate diagnostic, therapeutic, and preventative interventions. Junin, Machupo, Guanarito, Sabia, Lujo, and Lassa virus can all cause a viral haemorrhagic fever with high case fatality in hospitalised cases. Lassa fever is the most common severe arenavirus disease and is endemic across many low and middle income countries in West Africa, with an estimated 37.7 million people in 14 countries living in areas at risk of Lassa virus. Despite the discovery of Lassa virus in 1972 and an estimated 300,000 cases and 5000-10,000 deaths annually, there remain gaps in our understanding of the natural history of disease and in the availability of evidence based interventions.

The protocol has two components. Sites may implement one or both components.

1. Cardiovascular function in Lassa fever: Lassa fever in humans is often described in the literature as being characterized by vascular leak and shock in the terminal phase, this being the main pathway to death. Whilst animal data supports this, there are very limited data in humans. One of the main aims 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 to improve vascular leak.
2. Ribavirin pharmacokinetics and pharmacodynamics: The recommended treatment for Lassa is ribavirin, but its efficacy has not been established in randomized controlled trials and its mechanism of action is not fully understood. There are very limited PK data on ribavirin in patients with Lassa fever and the optimal dose of ribavirin for an RCT has not been established. Furthermore, there are various hypothesized mechanisms of action of ribavirin, none of which have been investigated in humans with Lassa fever. Therefore, further aims of this study are to characterize the PK of ribavirin and ribavirin metabolites (RMP, RDP, RTP) in Lassa fever patients and to identify potential mechanisms of action ribavirin in Lassa fever. Understanding Ribavirin's mechanism of action in Lassa fever is important for the optimal design of a future RCT.

Detailed description: Summary of cardiovascular function study Lassa fever carries a treated mortality in hospitalized patients of up to 30%. 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. A further 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.

Summary of ribavirin pharmacokinetics and pharmacodynamics sub-study Lassa fever carries a treated mortality in hospitalized patients of up to 30% in Nigeria. Ribavirin is the current standard of care. However, the efficacy of ribavirin has not been established in RCTs. There is very limited PK data on ribavirin in patients with Lassa fever and the optimal dose of ribavirin for an RCT is unknown. The aim of this study is to characterize the PK of ribavirin in Lassa fever, and identify any associations between ribavirin PK parameters and viral load and markers of inflammatory status.

Eligibility criteria: Cardiovascular Study:

Inclusion Criteria:

* Suspected or RT-PCR confirmed Lassa fever diagnosis
* Aged 10 years or above

Exclusion Criteria:

• None

Ribavirin PK/PD study

Inclusion Criteria:

* Suspected or RT-PCR confirmed Lassa fever diagnosis
* Patient will receive ribavirin therapy
* Aged 10 years or above

Exclusion Criteria:

• None

Primary outcomes:
measure: Cardiovascular
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacokinetics
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacodynamics
timeFrame: 5 days
Secondary outcomes:
measure: Cardiovascular
timeFrame: through study completion, an average of 2 weeks
measure: Cardiovascular
timeFrame: through study completion, an average of 2 weeks
measure: Cardiovascular
timeFrame: through study completion, an average of 2 weeks
measure: Cardiovascular
timeFrame: through study completion, an average of 2 weeks
measure: Cardiovascular
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacokinetics
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacokinetics
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacokinetics
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacokinetics
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacokinetics
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacokinetics
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacokinetics
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacokinetics
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacodynamics
timeFrame: 10 days
measure: Ribavirin Pharmacodynamics
timeFrame: 10 days
measure: Ribavirin Pharmacodynamics
timeFrame: 10 days
measure: Ribavirin Pharmacodynamics
timeFrame: 10 days
measure: Ribavirin Pharmacodynamics
timeFrame: 5 days
measure: Ribavirin Pharmacodynamics
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacodynamics
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacodynamics
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacodynamics
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacodynamics
timeFrame: through study completion, an average of 2 weeks
Other outcomes:
measure: Cardiovascular Explanatory
timeFrame: through study completion, an average of 2 weeks
measure: Cardiovascular Explanatory
timeFrame: through study completion, an average of 2 weeks
measure: Cardiovascular Explanatory
timeFrame: through study completion, an average of 2 weeks
measure: Cardiovascular Explanatory
timeFrame: through study completion, an average of 2 weeks
measure: Cardiovascular Explanatory
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacokinetics Explanatory
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacokinetics Explanatory
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacokinetics Explanatory
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacokinetics Explanatory
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacokinetics Explanatory
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacodynamics Explanatory
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacodynamics Explanatory
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacodynamics Explanatory
timeFrame: through study completion, an average of 2 weeks
measure: Ribavirin Pharmacodynamics Explanatory
timeFrame: through study completion, an average of 2 weeks
Locations:
city: Owo
country: Nigeria
facility: Owo Federal Medical Centre
state: Ondo State
Study officials:
References: