Lassa FeverNCT04285034
Cardiovascular Function and Ribavirin PK/PD in Lassa Fever in Lassa Fever
An observational study of Lassa Fever, run by University of Oxford at 1 site in Nigeria.
Trial 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. Read more about this study
- Who is it for?
- Ages 10 years and older
- Conditions the study is for
- Lassa Fever
- How many people
- 158 participants
- Where
- 1 siteNigeria
- Study dates
- 26 Nov 2019to 15 Jul 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients admitted to Lassa fever treatment centres with a diagnosis of suspected or RT-PCR confirmed Lassa fever.
Who may be able to join
- Suspected or RT-PCR confirmed Lassa fever diagnosis
- Aged 10 years or above
- Suspected or RT-PCR confirmed Lassa fever diagnosis
- Patient will receive ribavirin therapy
- Aged 10 years or above
Who cannot join
- None
- Ribavirin PK/PD study
- None
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Cardiovascular Function and Ribavirin Pharmacokinetics and Pharmacodynamics in Lassa Fever Patients in Nigeria: a Prospective Observational Cohort Study
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.
- 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.
- 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.
Read the 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.
- Conditions
- Lassa Fever
- Medical subject headings
- Lassa Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiovascular
Mean Arterial Pressure is less than 65mmHg or Systolic Blood Pressure is less than 90mmgHg or pulse pressure < 20mmHg
Measured: 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
Measured: through study completion, an average of 2 weeks
Ribavirin Pharmacodynamics
Change in Lassa virus Viral Load from baseline to day 5
Measured: 5 days
Secondary outcomes (23)
Cardiovascular
To identify the frequency of shock
Measured: through study completion, an average of 2 weeks
Cardiovascular
To identify the frequency of persistent shock
Measured: through study completion, an average of 2 weeks
Cardiovascular
To identify the frequency of respiratory distress
Measured: through study completion, an average of 2 weeks
Cardiovascular
To identify the frequency of shock and respiratory distress
Measured: through study completion, an average of 2 weeks
Cardiovascular
To identify the frequency of Death
Measured: through study completion, an average of 2 weeks
Ribavirin Pharmacokinetics
Proportion of patients with ribavirin CMIN above the IC50 at all measured CMIN during therapy
Measured: through study completion, an average of 2 weeks
Ribavirin Pharmacokinetics
Duration of time that ribavirin levels are above the IC90 and IC50
Measured: through study completion, an average of 2 weeks
Ribavirin Pharmacokinetics
Calculation of AUC [AUC∞ and AUCLAST] (ribavirin, ribavirin metabolites)
Measured: through study completion, an average of 2 weeks
Ribavirin Pharmacokinetics
Calculation of CMAX (ribavirin, ribavirin metabolites)
Measured: through study completion, an average of 2 weeks
Ribavirin Pharmacokinetics
Calculation of CMIN (ribavirin, ribavirin metabolites)
Measured: through study completion, an average of 2 weeks
Ribavirin Pharmacokinetics
Calculation of T1/2 (ribavirin, ribavirin metabolites)
Measured: through study completion, an average of 2 weeks
Ribavirin Pharmacokinetics
Volume of distribution (ribavirin, ribavirin metabolites)
Measured: through study completion, an average of 2 weeks
Ribavirin Pharmacokinetics
Calculation of Clearance (ribavirin, ribavirin metabolites)
Measured: through study completion, an average of 2 weeks
Ribavirin Pharmacodynamics
Change in Lassa virus Viral Load from baseline to day 3 and day 10
Measured: 10 days
Ribavirin Pharmacodynamics
Change in AST, ALT concentrations from baseline to day 3, 5, 10
Measured: 10 days
Ribavirin Pharmacodynamics
Change in eGFR from baseline to day 3, 5, 10
Measured: 10 days
Ribavirin Pharmacodynamics
Change in Haemoglobin from baseline to day 5, 10
Measured: 10 days
Ribavirin Pharmacodynamics
Change in ISG expression from baseline to day 3, 5
Measured: 5 days
Ribavirin Pharmacodynamics
Time to negative blood RT-PCR for Lassa virus
Measured: through study completion, an average of 2 weeks
Ribavirin Pharmacodynamics
Requirement for blood transfusion during hospitalisation
Measured: through study completion, an average of 2 weeks
Ribavirin Pharmacodynamics
Reaching KDIGO stage 3 during hospitalisation
Measured: through study completion, an average of 2 weeks
Ribavirin Pharmacodynamics
Requirement for dialysis during hospitalisation
Measured: through study completion, an average of 2 weeks
Ribavirin Pharmacodynamics
Duration of hospitalisation
Measured: through study completion, an average of 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2020
- Study start26 Nov 2019
- Primary completion15 Jul 2021
- Study completion15 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lassa FeverStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 158 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04285034
- Sponsor's protocol ID
- 04-19
- Status last verified
- Oct 2021
- First submitted
- 18 Feb 2020
- Last updated
- 13 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiovascular Function and Ribavirin Pharmacokinetics and Pharmacodynamics in Lassa Fever Patients in Nigeria: a Prospective Observational Cohort Study
- ClinicalTrials.gov ID
- NCT04285034
- Acronym / sponsor ID
- 04-19
- Conditions
- Lassa Fever
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 158 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- 26 Nov 2019 (actual)
- Primary completion
- 15 Jul 2021 (actual)
- Study completion
- 15 Jul 2021 (actual)
- First posted
- 26 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- 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.
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 10 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients admitted to Lassa fever treatment centres with a diagnosis of suspected or RT-PCR confirmed Lassa fever.
Key inclusion criteria (5 listed)
- Suspected or RT-PCR confirmed Lassa fever diagnosis
- Aged 10 years or above
- Suspected or RT-PCR confirmed Lassa fever diagnosis
- Patient will receive ribavirin therapy
- Aged 10 years or above
Key exclusion criteria (3 listed)
- None
- Ribavirin PK/PD study
- None
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Cardiovascular
Time frame: through study completion, an average of 2 weeks
Mean Arterial Pressure is less than 65mmHg or Systolic Blood Pressure is less than 90mmgHg or pulse pressure < 20mmHg
Ribavirin Pharmacokinetics
Time frame: through study completion, an average of 2 weeks
Proportion of patients with ribavirin CMIN above the IC90 at > 80% of measured CMIN during therapy
Ribavirin Pharmacodynamics
Time frame: 5 days
Change in Lassa virus Viral Load from baseline to day 5
23 secondary outcomes
Cardiovascular
Time frame: through study completion, an average of 2 weeks
Cardiovascular
Time frame: through study completion, an average of 2 weeks
Cardiovascular
Time frame: through study completion, an average of 2 weeks
Cardiovascular
Time frame: through study completion, an average of 2 weeks
Cardiovascular
Time frame: through study completion, an average of 2 weeks
Ribavirin Pharmacokinetics
Time frame: through study completion, an average of 2 weeks
Ribavirin Pharmacokinetics
Time frame: through study completion, an average of 2 weeks
Ribavirin Pharmacokinetics
Time frame: through study completion, an average of 2 weeks
Ribavirin Pharmacokinetics
Time frame: through study completion, an average of 2 weeks
Ribavirin Pharmacokinetics
Time frame: through study completion, an average of 2 weeks
Ribavirin Pharmacokinetics
Time frame: through study completion, an average of 2 weeks
Ribavirin Pharmacokinetics
Time frame: through study completion, an average of 2 weeks
Ribavirin Pharmacokinetics
Time frame: through study completion, an average of 2 weeks
Ribavirin Pharmacodynamics
Time frame: 10 days
Ribavirin Pharmacodynamics
Time frame: 10 days
Ribavirin Pharmacodynamics
Time frame: 10 days
Ribavirin Pharmacodynamics
Time frame: 10 days
Ribavirin Pharmacodynamics
Time frame: 5 days
Ribavirin Pharmacodynamics
Time frame: through study completion, an average of 2 weeks
Ribavirin Pharmacodynamics
Time frame: through study completion, an average of 2 weeks
Ribavirin Pharmacodynamics
Time frame: through study completion, an average of 2 weeks
Ribavirin Pharmacodynamics
Time frame: through study completion, an average of 2 weeks
Ribavirin Pharmacodynamics
Time frame: through study completion, an average of 2 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Lassa Fever, run by University of Oxford at 1 site in Nigeria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Nigeria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cardiovascular (time frame: through study completion, an average of 2 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2021.