LAssa Fever Adjunct Treatment With DEXamethasone
ConditionLassa Fever
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorBernhard Nocht Institute for Tropical Medicine
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 18 years
LF confirmed by RT-PCR (reverse-transcription polymerase chain reaction) with a cycle threshold (Ct) value < 30
Alert, confusion, voice, pain, unresponsive (ACVPU) other than A
Systolic blood pressure < 90 mmHg
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Dexamethasone
DrugDexamethasone 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.
Ribavirin
DrugRibavirin 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.
Treatment groups
42 Participants
are divided into 2 treatment groupsGroup A: Standard of careActive comparator 1 intervention
Group B: Standard of care + dexamethasoneExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Proportion of treatment emergent adverse events and treatment emergent serious adverse events
Documentation of events
Time frame
Participants will be followed up until day 10 after enrollment.Secondary outcomes
1
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);
Time frame
Participants will be followed up until day 10 after enrollment.2
Mean/median decline and area under the curve (AUC) of AST, ALT, CK, LDH and CRP
Blood analyses
Time frame
Participants will be followed up until day 10 after enrollment.3
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.
Time frame
Participants will be followed up until day 10 after enrollment.4
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.
Time frame
Participants will be followed up until day 10 after enrollment.Sponsors and contacts
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Source ClinicalTrials.gov