Lassa FeverPhase 2LADEXNCT06222723
LAssa Fever Adjunct Treatment With DEXamethasone
A Phase 2 study testing Dexamethasone and Ribavirin in people with Lassa Fever, run by Bernhard Nocht Institute for Tropical Medicine at 1 site in Nigeria.
Trial summary
Dexamethasone is a corticosteroid which can modulate inflammatory-mediated tissue damage associated with a wide range of infectious diseases. Dexamethasone is routinely used for treatment of tuberculous meningitis and for pneumococcal meningitis in adults. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lassa Fever
- What is being tested?
- Dexamethasone and Ribavirin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteNigeria
- Study dates
- 5 Feb 2024to Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- LF confirmed by RT-PCR (reverse-transcription polymerase chain reaction) with a cycle threshold (Ct) value < 30
- Signs of significant health impairment as evidenced by any of the following:
- Alert, confusion, voice, pain, unresponsive (ACVPU) other than A
- Systolic blood pressure < 90 mmHg
- Seizure(s), meningism, coma, focal neurological deficit
Show all 11Show fewer
- AST (GOT) >3xULN
- ALT (GPT) > 3xULN
- KDIGO 2 or more severe based on serum creatinine only
- Active macroscopic bleeding
- O2 saturation < 92
Who cannot join
- Pregnancy (evidenced by positive urine pregnancy test in women of child-bearing potential)
- Lactation following live birth
- Known intolerance and contra-indications to ribavirin or dexamethasone
- Patients who already received a corticosteroid within the preceding 7 days
- Investigator's valuation that patient might be put to substantial risk by participating in this trial
- Patients receiving end-of-life care as judged by the investigator
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Nigeria1 site, 1 recruiting
- Recruiting
Irrua Specialist Teaching Hospital
Irrua, Edo
Sylvanus Okogbenin, Prof, +2348060476179, okogbenins@yahoo.co.uk
Cyril Erameh, Dr, +2348032413382, cyrilerameh@gmail.com
About this study
Official title: Safety and Tolerability of Adjunct Dexamethasone in Addition to Standard of Care Antiviral Therapy Compared to Standard of Care Antiviral Therapy Alone for the Treatment of Moderate to Severe Lassa Fever
Dexamethasone is a corticosteroid which can modulate inflammatory-mediated tissue damage associated with a wide range of infectious diseases. Dexamethasone is routinely used for treatment of tuberculous meningitis and for pneumococcal meningitis in adults. In Coronavirus Disease 2019 (COVID-19) dexamethasone is also effectively preventing immune mediated damage of the lungs. There is also indication that dexamethasone may be promising in severe LF.
Read the detailed description
Lassa fever (LF) is a severe and often fatal systemic disease in humans. It is caused by the Lassa virus (LASV). Vaccines are not available yet and treatment options are limited to supportive care and ribavirin. Recent LF outbreaks in Nigeria showed an exceptionally high and increasing incidence of LF cases LF affects a large number of countries in West Africa. The pathophysiology of LF is not fully understood yet. It is hypothesized that the damage mediated by the host's defence is plays a key role in the pathophysiology of severe LF. Dexamethasone is considered to dampen the overactive immune response in a range of infectious diseases and thus preventing consecutive damage mediated by the host's immune system, while the antiinfective therapy is effectively treating the underlying pathogen. At the Irrua Specialist Teaching Hospital (ISTH) in Nigeria, one of the largest treatment centres for LF in West-Africa, dexamethasone has been successfully used in clinical practice to manage co-infections of LASV and Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).
To evaluate Dexamethasone for the treatment of moderate to severe LF cases, a prospective open label randomized controlled phase II clinical trial will be conducted:
- Standard of care antiviral ribavirin therapy
- Standard of care antiviral ribavirin therapy + dexamethasone
The primary objective is to assess safety and tolerability of dexamethasone in moderate to severe LF when administered as adjunct treatment. Secondary objectives are to assess the effect of the study intervention on disease progression; to assess immunological and virological impact of dexamethasone therapy and the characterization of population pharmacokinetic characteristics for patients treated with adjunct dexamethasone therapy.
- Conditions
- Lassa Fever
- Being tested
- Dexamethasone, Ribavirin
- Medical subject headings
- Lassa Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
Dexamethasone will be administered for 10 days. For the first 48 hours, dexamethasone will be given iv. After 48 hours, a switch to oral dexamethasone (same dosage) is permitted at the discretion of the study physician.
RibavirinDrug
Ribavirin treatment will be administered iv for 10 days, as recommended in the Nigeria Centre for Disease Control and Prevention National Guidelines for LF Case Management.
| Study group | Role | What they receive |
|---|---|---|
| Standard of care | Active comparator | Standard of care antiviral ribavirin therapy Receives: Drug: Ribavirin |
| Standard of care + dexamethasone | Experimental | Standard of care antiviral ribavirin therapy + dexamethasone Receives: Drug: Dexamethasone; Drug: Ribavirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of treatment emergent adverse events and treatment emergent serious adverse events
Documentation of events
Measured: Participants will be followed up until day 10 after enrollment.
Secondary outcomes (10)
Unfavourable outcome
The outcome is measured by the proportion of participants reaching a composite endpoint.
The outcome is reached if there is a new onset of any of the following: acute kidney injury (KDIGO 3), acute respiratory distress syndrome (SpO2/FiO2 ≤ 315), shock (mean blood pressure < 65 mmHg or systolic blood pressure < 90 mmHg ), encephalopathy (CVPU or seizure), death (yes/no);
Measured: Participants will be followed up until day 10 after enrollment.
Mean/median decline and area under the curve (AUC) of AST, ALT, CK, LDH and CRP
Blood analyses
Measured: Participants will be followed up until day 10 after enrollment.
Description of: proinflammatory plasma cytokine levels and lymphocyte phenotype under treatment
Assays such as the enzyme-linked immunosorbent assays (ELISA) and/or immunofluorescence assays will be used to retrospectively determine LASV IgM and IgG, as well as further IgG subclassification if needed, and to monitor the development of LASV specific antibodies in blood.
Longitudinal development of inflammatory biomarkers such as IFNα, TNFα, IL-6, and IL-8 will be measured in plasma using bead-based multiplex assays. The phenotype of lymphocytes will be described using flow cytometry.
Measured: Participants will be followed up until day 10 after enrollment.
Description of evolution of viral loads and infectious titers over time until day 10
Virus titers will be determined. Viral growth, isolation of LASV in cell culture, virus sequencing and unbiased metagenomic sequencing will be used on selected samples to study the longitudinal impact of drug treatment (ribavirin and dexamethasone) on LASV genomes.
Measured: Participants will be followed up until day 10 after enrollment.
Evolution of selected virus gene sequences under treatment
Virus sequencing
Measured: Participants will be followed up until day 10 after enrollment.
Peak plasma concentration (Cmax)
Compartmental analysis
Measured: Participants will be followed up until day 10 after enrollment.
Time to peak plasma concentration (Tmax)
Compartmental analysis
Measured: Participants will be followed up until day 10 after enrollment.
Area under the plasma concentration versus time curve (AUC)
Compartmental analysis
Measured: Participants will be followed up until day 10 after enrollment.
Half life (T 1/2)
Compartmental analysis
Measured: Participants will be followed up until day 10 after enrollment.
Volume of distribution (Vd)
Compartmental analysis
Measured: Participants will be followed up until day 10 after enrollment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2024
- Study start5 Feb 2024
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
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.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bernhard Nocht Institute for Tropical Medicine
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Stephan Günther, Prof., Study director, Bernhard Nocht Institute for Tropical Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06222723
- Sponsor's protocol ID
- 1.0 (17 July 2023)
- Other IDs
- 20231908/486, 2023-101164-BO-ff, 2023
- Acronym
- LADEX
- Status last verified
- Feb 2025
- First submitted
- 29 Sep 2023
- Last updated
- 6 Feb 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Case by case decision upon request
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Tolerability of Adjunct Dexamethasone in Addition to Standard of Care Antiviral Therapy Compared to Standard of Care Antiviral Therapy Alone for the Treatment of Moderate to Severe Lassa Fever
- ClinicalTrials.gov ID
- NCT06222723
- Acronym / sponsor ID
- LADEX / 1.0 (17 July 2023)
- Conditions
- Lassa Fever
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Bernhard Nocht Institute for Tropical MedicineOther government
- Study start
- 5 Feb 2024 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 25 Jan 2024 (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.
Dexamethasone is a corticosteroid which can modulate inflammatory-mediated tissue damage associated with a wide range of infectious diseases. Dexamethasone is routinely used for treatment of tuberculous meningitis and for pneumococcal meningitis in adults. In Coronavirus Disease 2019 (COVID-19) dexamethasone is also effectively preventing immune mediated damage of the lungs. There is also indication that dexamethasone may be promising in severe LF.
Detailed description
Lassa fever (LF) is a severe and often fatal systemic disease in humans. It is caused by the Lassa virus (LASV). Vaccines are not available yet and treatment options are limited to supportive care and ribavirin. Recent LF outbreaks in Nigeria showed an exceptionally high and increasing incidence of LF cases LF affects a large number of countries in West Africa. The pathophysiology of LF is not fully understood yet. It is hypothesized that the damage mediated by the host's defence is plays a key role in the pathophysiology of severe LF. Dexamethasone is considered to dampen the overactive immune response in a range of infectious diseases and thus preventing consecutive damage mediated by the host's immune system, while the antiinfective therapy is effectively treating the underlying pathogen. At the Irrua Specialist Teaching Hospital (ISTH) in Nigeria, one of the largest treatment centres for LF in West-Africa, dexamethasone has been successfully used in clinical practice to manage co-infections of LASV and Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).
To evaluate Dexamethasone for the treatment of moderate to severe LF cases, a prospective open label randomized controlled phase II clinical trial will be conducted:
- Standard of care antiviral ribavirin therapy
- Standard of care antiviral ribavirin therapy + dexamethasone
The primary objective is to assess safety and tolerability of dexamethasone in moderate to severe LF when administered as adjunct treatment. Secondary objectives are to assess the effect of the study intervention on disease progression; to assess immunological and virological impact of dexamethasone therapy and the characterization of population pharmacokinetic characteristics for patients treated with adjunct dexamethasone therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard of care | Active comparator | Drug: RibavirinStandard of care antiviral ribavirin therapy |
| Standard of care + dexamethasone | Experimental | Drug: Dexamethasone, Drug: RibavirinStandard of care antiviral ribavirin therapy + dexamethasone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age ≥ 18 years
- LF confirmed by RT-PCR (reverse-transcription polymerase chain reaction) with a cycle threshold (Ct) value < 30
- Signs of significant health impairment as evidenced by any of the following:
- Alert, confusion, voice, pain, unresponsive (ACVPU) other than A
- Systolic blood pressure < 90 mmHg
Key exclusion criteria (6 listed)
- Pregnancy (evidenced by positive urine pregnancy test in women of child-bearing potential)
- Lactation following live birth
- Known intolerance and contra-indications to ribavirin or dexamethasone
- Patients who already received a corticosteroid within the preceding 7 days
- Investigator's valuation that patient might be put to substantial risk by participating in this trial
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexamethasoneDexamethasone will be administered for 10 days. For the first 48 hours, dexamethasone will be given iv. After 48 hours, a switch to oral dexamethasone (same dosage) is permitted at the discretion of the study physician. | Drug | Standard of care + dexamethasone |
| RibavirinRibavirin treatment will be administered iv for 10 days, as recommended in the Nigeria Centre for Disease Control and Prevention National Guidelines for LF Case Management. | Drug | Standard of care, Standard of care + dexamethasone |
Primary outcome
Proportion of treatment emergent adverse events and treatment emergent serious adverse events
Time frame: Participants will be followed up until day 10 after enrollment.
Documentation of events
10 secondary outcomes
Unfavourable outcome
Time frame: Participants will be followed up until day 10 after enrollment.
Mean/median decline and area under the curve (AUC) of AST, ALT, CK, LDH and CRP
Time frame: Participants will be followed up until day 10 after enrollment.
Description of: proinflammatory plasma cytokine levels and lymphocyte phenotype under treatment
Time frame: Participants will be followed up until day 10 after enrollment.
Description of evolution of viral loads and infectious titers over time until day 10
Time frame: Participants will be followed up until day 10 after enrollment.
Evolution of selected virus gene sequences under treatment
Time frame: Participants will be followed up until day 10 after enrollment.
Peak plasma concentration (Cmax)
Time frame: Participants will be followed up until day 10 after enrollment.
Time to peak plasma concentration (Tmax)
Time frame: Participants will be followed up until day 10 after enrollment.
Area under the plasma concentration versus time curve (AUC)
Time frame: Participants will be followed up until day 10 after enrollment.
Half life (T 1/2)
Time frame: Participants will be followed up until day 10 after enrollment.
Volume of distribution (Vd)
Time frame: Participants will be followed up until day 10 after enrollment.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2025.
- Individual participant dataSharing planned: No. Case by case decision upon request
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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.
Stephan Günther, Prof. study director
Bernhard Nocht Institute for Tropical Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dexamethasone and Ribavirin in people with Lassa Fever, run by Bernhard Nocht Institute for Tropical Medicine 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 11 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 6 Feb 2025. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mirjam Groger, Dr. (+4940285380480, groger@bnitm.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of treatment emergent adverse events and treatment emergent serious adverse events (time frame: Participants will be followed up until day 10 after enrollment.). 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 6 Feb 2025.