Condition category
Infections and Infestations
Date applied
02/02/2020
Date assigned
06/02/2020
Last edited
07/02/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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

https://www.tropmed-hamburg.de

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

Publication citations

Additional files

Editorial Notes

07/02/2020: Internal review. 05/02/2020: Trial’s existence confirmed by Human Research Ethics Committee of ISTH (Irrua Specialist Teaching Hospital)