Anakinra in Dengue With Hyperinflammation ( AnaDen )

Oxford University Clinical Research Unit, Vietnam

Status and phase: Active, not recruiting; Phase 2

Conditions: Dengue; Hyperinflammatory Syndrome; Anti-inflammatory Agents; Anakinra; Severe Dengue; Immuno-modulation; Macrophage Activation Syndrome; Dengue With Warning Signs; Cytokine Storm

Treatments: Drug: Anakinra; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05611710

223004/Z/21/Z (Other Grant/Funding Number)

60DX

Details and patient eligibility

About

This study aims to evaluate the effect of anakinra in dengue patients with hyperinflammation as compared to placebo

Primary Objective:

To evaluate the efficacy of Anakinra in moderate-severe dengue patients with hyperinflammation.

Secondary Objectives:

• To assess the safety of anakinra therapy in dengue with hyperinflammation
• To assess the effect of anakinra therapy in patients with dengue on physiological, clinical and virological parameters
• To assess the immunomodulation effects of anakinra in dengue
• Immune cell signatures in dengue with and without anakinra
• To assess difference in gene expression between treatment group compared to non-treatment population

Full description

This is a randomized double blinded placebo controlled trial investigating the effects of four days of anakinra treatment on dengue patients with hyperinflammatory syndrome. The anakinra/placebo will be given to eligible participants admitted to the Hospital for Tropical Diseases (HTD) in Ho Chi Minh City, Vietnam. 160 dengue patients will be randomly assigned to either anakinra or placebo intervention group to receive treatment for 4 days.

Patients admitted to the HTD with a clinical diagnosis of dengue and at least 1 warning sign(s) or severe dengue to Emergency department / inpatient wards / Intensive Care Units (ICU), will be invited to participate in the trial.

Eligible patients will be invited to participate in the screening phase during which, the collection of clinical information about this acute illness episode as well as some screening tests will be performed, including measurement ferritin, creatinine, pregnancy test (for all females).

- If ferritin level is greater than 2000ng/mL and meet all other inclusion/exclusion criteria, patients will be invited to participate in the randomization phase (second consent), which they will be randomly given either anakinra or placebo intravenous (IV) for four days.

The intervention:

• (i) 200mg bid for four days in adults participants (≥ 16 years) or in children (12-16 years), with weight > 50kg; and
• (ii) 2mg/kg bid for four days in children (12-16 years), with weight < 50Kg.

All patients will be followed up daily at the clinical wards until discharge.

Details of all AEs and SAEs will be recorded on specific forms, together with an assessment as to whether the events are likely to have been related to any treatment received. All SAEs will be reported promptly to the DMC and ECs according to policy. In cases of discontinuation due to AEs, participants will be followed up until the events have resolved or stabilized.

Enrollment: 160 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients hospitalised with a clinical diagnosis of dengue and at least 1 warning sign(s) (see appendix) or severe dengue to Emergency department/inpatient wards/Intensive Care wards (ICU),
• Ferritin levels > 2000ng/mL
• ≥ 12 years of age
• Written informed consent or assent to participate in the study
• Agree to come back for 2 follow up visits around day 30 of illness (maximum 5 weeks) and at 3 months

Exclusion criteria

• Pregnancy
• Localizing features suggesting an alternative/additional diagnosis, e.g. pneumonia, sepsis
• Patients taking immunosuppressive drugs or other biologics in last 1 month
• Patients with underlying malignancy or immunosuppression
• Children <12 years
• Have end-stage renal failure (baseline GFR < 30ml/min)
• Being treated for TB
• Taking any drug with significant interaction with anakinra
• The study physician judges that the patient is unlikely to attend follow up visit at around 3-4 weeks after fever onset - e.g. due to long travelling distance from the clinic

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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160 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

The control group will be formed of 80 dengue patients with warning signs or severe dengue receiving placebo.

Treatment:

Drug: Placebo

Anakinra

Experimental group

Description:

The intervention group will include 80 dengue patients with warning signs or severe dengue receiving anakinra.

Treatment:

Drug: Anakinra