Plain English Summary
Background and study aims
Lassa fever (LF) is a severe and often fatal systemic disease in humans. It is caused by Lassa virus (LASV) which belongs to the segmented negative-strand RNA viruses of the family Arenaviridae. LF affects a large number of countries in West Africa. The currently used antiviral, which is also recommended by WHO, is ribavirin. However, evidence for ribavirin efficacy in LF patients is poor and pharmacokinetic (PK) data for currently used regimens are not available. This study will describe blood concentrations of ribavirin and will provide evidence for further dose optimization studies with the ultimate goal of improving patient care.
Who can participate?
Patients aged 18 years or older, suffering from Lassa fever.
What does the study involve?
Participants will receive ribavirin treatment using the Irrua hospital dosing regimen.
Blood samples will be collected at 0.5, 1, 3, 5, 8, 12 and 24 hours after doses on day 1, day 4 and day 10.
What are the possible benefits and risks of participating?
Benefits: Participants will be provided with protein bars and long-lasting insecticide-treated bednets as compensation for taking part in this observational study.
Risks: Participants may experience side effects from taking the drug.
Where is the study run from?
Irrua Specialist Teaching Hospital (Nigeria)
When is the study starting and how long is it expected to run for?
February 2020 to December 2021
Who is funding the study?
Federal German Ministry for Health (Germany)
Who is the main contact?
Dr Mirjam Groger
groger@bnitm.de
Trial website
Contact information
Type
Public
Primary contact
Dr Mirjam Groger
ORCID ID
http://orcid.org/0000-0001-7375-3685
Contact details
Bernhard Nocht Institute for Tropical Medicine
Hamburg
20359
Germany
+49 4042818511
groger@bnitm.de
Additional identifiers
EudraCT number
Nil known
ClinicalTrials.gov number
Nil known
Protocol/serial number
v03 06DEC2019, amended version of v02 25OCT2019
Study information
Scientific title
Prospective observational study on the pharmacokinetic properties of the Irrua ribavirin regimen used in routine clinical practice in Lassa fever patients in Nigeria
Acronym
PAIR
Study hypothesis
Evaluating the pharmacokinetic (PK) characteristics of ribavirin when administered as per local standard in a national reference centre for treatment of Lassa fever (LF). Descriptive analysis of drug exposure and viral kinetics will be performed to elucidate the PK/PD (pharmacodynamic) profile of ribavirin in the treatment of LF.
Ethics approval
Approved 07/11/2019, Human Research Ethics Committee of ISTH (Irrua Specialist Teaching Hospital, km87 Benin Auchi Road, Irrua, P.M.B. 8 Edo State, Nigeria; +234 815 299 8878; isth.rec.2015@gmail.com), ref: ISTH/HREC/20190104/009
Study design
Prospective observational clinical study
Primary study design
Observational
Secondary study design
Longitudinal study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
No participant information sheet available
Condition
Lassa fever
Intervention
Pharmacokinetic analysis of ribavirin treatment
Blood samples will be collected at 0.5, 1, 3, 5, 8, 12 and 24 hours after doses on day 1, day 4 and day 10 of ribavirin treatment using the Irrua dosing regimen. Additionally, blood will be collected during screening before the first dose of ribavirin. Blood samples will be centrifuged and the plasma supernatant will be frozen at -80° C within 2 h after blood sampling. Plasma samples will be inactivated using a validated protocol. The samples will then be shipped frozen to the bioanalysis site (Dept. of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, Germany). Ribavirin plasma concentrations will be determined using liquid chromatography coupled to tandem mass spectrometry (LCMS/ MS).
PCR analyses
Blood for RT-PCR, LASV serology and metagenomic sequencing will be sampled at inclusion, 24 hours after first drug administration and then every second day until end of treatment. Two RT-PCR assays for the detection of LASV, Altona Diagnostics (Hamburg, Germany) and an inhouse assay will be used to determine the viral load. These analyses will be performed at site in Irrua.
Biochemistry and hematology
Blood for biochemical safety and tolerability will be collected every second day starting with screening. Biochemistry and hematology analyses will be performed using automated systems at ISTH.
Intervention type
Drug
Phase
Phase IV
Drug names
Ribavirin
Primary outcome measure
Pharmacokinetic parameters (maximum concentration (Cmax), maximum time (Tmax), area under the curve (AUC), half-life time (T1/2), volume of distribution) using blood samples will be collected at 0.5, 1, 3, 5, 8, 12 and 24 hours after doses on day 1, day 4 and day 10 of ribavirin treatment using the Irrua dosing regimen
Secondary outcome measures
1. Safety and tolerability of the Irrua Ribavirin regimen measured using clinical, hematological, and biochemical parameters:
1.1. Clinical: every day from day 0 to day 10
1.2. Haematology: standarad full blood count (hb; wbc; pla; diff) every 48 hours
1.3. Biochemistry: creatinine; alt; ast; bun; ldh every 48 hours
2. Viral kinetics in patients measured using at day 0, 5, 10
3. LASV genome changes under the Irrua ribavirin regimen measured at day 0, 5, 10
Overall trial start date
01/06/2019
Overall trial end date
31/12/2021
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Age ≥ 18 years
2. Lassa fever confirmed by RT-PCR
3. Written informed consent
4. Anticipated treatment with intravenous ribavirin
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
20 evaluable patients
Participant exclusion criteria
1. Inability to give consent (e.g. unconscious patients/ cognitively impaired patients)
2. Critical illness (based on investigator’s clinical evaluation)
3. Severe malnutrition
4. Hemodialysis
5. History of hemophilia / bleeding disorder
6. Hematocrit <30 %
7. History of hemoglobinopathies (i.e., sickle-cell anaemia or thalassemia major)
8. Known intolerance to ribavirin
9. Known pregnancy
10. Women who plan to get pregnant within the upcoming 3 months
11. Patients who already received ribavirin within the last 7 days
Recruitment start date
06/02/2020
Recruitment end date
31/12/2021
Locations
Countries of recruitment
Nigeria
Trial participating centre
Irrua Specialist Teaching Hospital
km87 Benin Auchi Road
Irrua
P.M.B. 8 Edo State
Nigeria
Sponsor information
Organisation
Bernhard Nocht Institute for Tropical Medicine
Sponsor details
Bernhard Nocht Strasse 74
Hamburg
20359
Germany
+49 40 42818-930
GUENTHER@BNITM.DE
Sponsor type
Research organisation
Website
Funders
Funder type
Government
Funder name
Bundesministerium für Gesundheit
Alternative name(s)
Federal Ministry of Health, Germany, Federal Ministry of Health, BMG
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
Germany
Results and Publications
Publication and dissemination plan
All results will be published in agreement between the Sponsor and the PI in international peer-reviewed scientific journals with preference to open access journals.
IPD sharing statement:
All data generated or analysed during this study will be included in the subsequent results publication.
Intention to publish date
31/12/2022
Participant level data
Other
Basic results (scientific)
Publication list