Cardiovascular Function and Ribavirin PK/PD in Lassa Fever in Lassa Fever

NCT04285034 | Completed

• 1 other identifier: 04-19
• Study Type: observational
• Target: 158
• Locations: 1 country
• Sites: 1

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. 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. 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.

Conditions

Lassa Fever

Outcome Measures

Primary Outcomes (3)

• Cardiovascular

  Mean Arterial Pressure is less than 65mmHg or Systolic Blood Pressure is less than 90mmgHg or pulse pressure \< 20mmHg

  through study completion, an average of 2 weeks

• Ribavirin Pharmacokinetics

  Proportion of patients with ribavirin CMIN above the IC90 at \> 80% of measured CMIN during therapy

  through study completion, an average of 2 weeks

• Ribavirin Pharmacodynamics

  Change in Lassa virus Viral Load from baseline to day 5

  5 days

Secondary Outcomes (23)

• Cardiovascular

  through study completion, an average of 2 weeks

• Cardiovascular

  through study completion, an average of 2 weeks

• Cardiovascular

  through study completion, an average of 2 weeks

• Cardiovascular

  through study completion, an average of 2 weeks

• Cardiovascular

  through study completion, an average of 2 weeks

Other Outcomes (14)

• Cardiovascular Explanatory

  through study completion, an average of 2 weeks

• Cardiovascular Explanatory

  through study completion, an average of 2 weeks

• Cardiovascular Explanatory

  through study completion, an average of 2 weeks

Study Arms (2)

Ribavirin only

Patients will receive ribavirin in accordance with Nigerian treatment guidelines. Patients will either receive the McCormick regimen or the Irrua regimen. PK blood tests will be done on Day 1,2,5,6,10,11,12,13, discharge; Paxgene RNA blood test on day 1, 3, 5, discharge Haematocrit finger prick test on day 1,2, 5, 6, 10, discharge

Cardiocascular study only

Cardiac tests (NICAS (daily), ECG (Day 1, 5, 10, discharge), Echocardiogram (Day 1, 5, discharge), Ultrasound (Day 1, 3, 5, 7, 10), Endopat (Day 1 and discharge)) will be done throughout; Haematocrit finger prick test daily PAXgene RNA blood test on day 1, 5, discharge

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• None
• Ribavirin PK/PD study
• Suspected or RT-PCR confirmed Lassa fever diagnosis
• Patient will receive ribavirin therapy
• Aged 10 years or above
• None

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Owo Federal Medical Centre

Owo, Ondo State, PMB 1053, Nigeria

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

PAXGene (RNA) DBS and FTA cards

MeSH Terms

Conditions

Lassa Fever

Condition Hierarchy (Ancestors)

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

Study Design

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

Study Record Dates

• First Submitted: February 18, 2020
• First Posted: February 26, 2020
• Study Start: November 26, 2019
• Primary Completion: July 15, 2021
• Study Completion: July 15, 2021
• Last Updated: October 13, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

NG (1)