Clinical trial NCT06222723: LAssa Fever Adjunct Treatment With DEXamethasone
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Lassa Fever
Lead sponsor: Bernhard Nocht Institute for Tropical Medicine
Sponsor class: OTHER_GOV
First posted: 2024-01-25
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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:

1. Standard of care antiviral ribavirin therapy
2. 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.

Eligibility criteria: Inclusion Criteria:

* 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
* AST (GOT) \>3xULN
* ALT (GPT) \> 3xULN
* KDIGO 2 or more severe based on serum creatinine only
* Active macroscopic bleeding
* O2 saturation \< 92

Exclusion Criteria:

* 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

Primary outcomes:
measure: Proportion of treatment emergent adverse events and treatment emergent serious adverse events
timeFrame: Participants will be followed up until day 10 after enrollment.
Secondary outcomes:
measure: Unfavourable outcome
timeFrame: Participants will be followed up until day 10 after enrollment.
measure: Mean/median decline and area under the curve (AUC) of AST, ALT, CK, LDH and CRP
timeFrame: Participants will be followed up until day 10 after enrollment.
measure: Description of: proinflammatory plasma cytokine levels and lymphocyte phenotype under treatment
timeFrame: Participants will be followed up until day 10 after enrollment.
measure: Description of evolution of viral loads and infectious titers over time until day 10
timeFrame: Participants will be followed up until day 10 after enrollment.
measure: Evolution of selected virus gene sequences under treatment
timeFrame: Participants will be followed up until day 10 after enrollment.
measure: Peak plasma concentration (Cmax)
timeFrame: Participants will be followed up until day 10 after enrollment.
measure: Time to peak plasma concentration (Tmax)
timeFrame: Participants will be followed up until day 10 after enrollment.
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: Participants will be followed up until day 10 after enrollment.
measure: Half life (T 1/2)
timeFrame: Participants will be followed up until day 10 after enrollment.
measure: Volume of distribution (Vd)
timeFrame: Participants will be followed up until day 10 after enrollment.
Other outcomes:
Locations:
city: Irrua
country: Nigeria
facility: Irrua Specialist Teaching Hospital
state: Edo State
Study officials:
affiliation: Bernhard Nocht Institute for Tropical Medicine
name: Stephan Günther, Prof.
role: STUDY_DIRECTOR
References: