LAssa Fever Adjunct Treatment With DEXamethasone (LADEX)

Bernhard Nocht Institute for Tropical Medicine

Status and phase: Enrolling; Phase 2

Conditions: Lassa Fever

Treatments: Drug: Ribavirin; Drug: Dexamethasone

Study type: Interventional

Funder types: Other

Identifiers

NCT06222723

20231908/486 (Other Identifier)

1.0 (17 July 2023)

2023-101164-BO-ff (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 42 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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42 participants in 2 patient groups

Standard of care

Active Comparator group

Description:

Standard of care antiviral ribavirin therapy

Treatment:

Drug: Ribavirin

Standard of care + dexamethasone

Experimental group

Description:

Standard of care antiviral ribavirin therapy + dexamethasone

Treatment:

Drug: Dexamethasone

Drug: Ribavirin