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

Lassa Fever Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03889106
• Other study ID #: 38-18
• Status: Terminated
• Start date: March 1, 2019
• Est. completion date: October 1, 2020

Study information

• Verified date: March 2019
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: October 1, 2020
• Est. primary completion date: October 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years and older

Eligibility

Inclusion Criteria:

• Positive antigen or PCR test for Lassa fever

• Aged 10 years or above

Exclusion Criteria:

• Patients for end of life care only

Related Conditions & MeSH terms

• Fever
• Lassa Fever

Intervention

Drug:
• Ribavirin
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.

Locations

Country	Name	City	State
Sierra Leone	Kenema Government Hospital	Kenema

Sponsors (5)

Lead Sponsor	Collaborator
University of Oxford	Kenema Government Hospital, London School of Hygiene and Tropical Medicine, National Institute for Health Research, United Kingdom, Public Health England

Country where clinical trial is conducted

Sierra Leone, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cardiovascular function - primary	Death during hospitalization	Up to 28 days during hospitalisation
Primary	Ribavirin PK - primary	Proportion of patients with ribavirin CMIN above the IC90 at all measured CMIN during therapy	Up to 15 days during hospitalisation
Primary	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	Cardiovascular function - secondary	• Shock (shock is defined as a systolic BP < 90mmgHg [age specific in children] OR a MAP < 65mmgHg AND a lactate > 2 mEq/L)	Up to 28 days during hospitalisation
Secondary	Cardiovascular function - secondary	• Persistent shock (persistent shock is defined as a MAP < 65 mmHg OR a SBP < 90 mmHg [age specific in children] AND a lactate > 2 mEq/L on more than 2 occasions [at least 6 hours apart] DESPITE IV fluids +/- vasopressors)	Up to 28 days during hospitalisation
Secondary	Cardiovascular function - secondary	• Respiratory distress (respiratory distress is defined as a respiratory rate > 24 (age specific in children) AND oxygen saturations < 94% OR use of supplemental oxygen)	Up to 28 days during hospitalisation
Secondary	Ribavirin PK - secondary	• Proportion of patients with ribavirin CMIN above the IC50 at all measured CMIN during therapy	Up to 15 days during hospitalisation
Secondary	Ribavirin PK - secondary	• Peak Plasma Concentration	Up to 15 days during hospitalisation
Secondary	Ribavirin PK - secondary	• Minimum Plasma Concentration	Up to 15 days during hospitalisation
Secondary	Ribavirin PK - secondary	• Area under the plasma concentration versus time curve	Up to 15 days during hospitalisation
Secondary	Ribavirin PK - secondary	• Half life	Up to 15 days during hospitalisation
Secondary	Ribavirin PD (mechanism of action)	• Change in ISG expression from baseline to day 3/5	Up to 15 days during hospitalisation
Secondary	Ribavirin PD (mechanism of action)	• Change in RHI from baseline to day 3	Up to 15 days during hospitalisation
Secondary	Ribavirin PD (mechanism of action)	• Time to negative blood PCR for Lassa virus	Up to 15 days during hospitalisation
Secondary	Ribavirin PD (mechanism of action)	• Survival to hospital discharge	Up to 15 days during hospitalisation
Secondary	Ribavirin PD (mechanism of action)	Change in aspartate aminotransferase concentrations (units/litre) from baseline to day 3/5	Up to 15 days during hospitalisation
Secondary	Ribavirin PD (mechanism of action)	• Change in systemic nitric oxide concentrations from baseline to day 3/5	Up to 15 days during hospitalisation