Anakinra in Dengue With Hyperinflammation ( AnaDen )

Phase 2Active Not RecruitingNCT05611710

Oxford University Clinical Research Unit, Vietnam160 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Interventions

PlaceboDRUG

Drug: Placebo, with visually matched clear syringes * Adults (≥16 years) and children (12-16 years, \> 50Kg) will receive 2 syringes of placebo via IV route, twice daily for 4 days * Children (12-16 years, \< 50Kg) will receive no more than 1 syringe of placebo via IV route, twice daily for 4 days

AnakinraDRUG

Drug: Anakinra * Adults (≥16 years) and children (12-16 years, \> 50Kg) will receive 200mg of anakinra (2 syringes) via IV route, twice daily for 4 days * Children (12-16 years, \< 50Kg) will receive 2mg/Kg of anakinra via IV route, twice daily for 4 days (no more than 1 syringe of anakinra, twice daily for 4 days)

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Change in modified Sequential Organ Failure Assessment score (mSOFA core, modified for limited resource settings and dengue) within 4 days

Change in mSOFA score over 4 days after randomization (min score= 0, max score = 24, higher scores mean worse outcomes)

Time frame: baseline, up to day 4

Secondary Outcomes

Mortality

Number of death up to day 30

Time frame: Up to day 30

Change in modified Sequential Organ Failure Assessment score (mSOFA core, modified for limited resource settings and dengue) at day 7

Change in mSOFA score at day 7 post randomization (min score= 0, max score = 24, higher scores mean worse outcomes)

Time frame: baseline, day 7

Number of days treated in Intensive care unit (ICU)

Number of days treated in ICU

Time frame: Up to day 30

Number of days treated in hospital

Time frame: Up to day 30

Number of participants with Serious Adverse Events (SAEs)

Number of participants having SAEs within 2 time-periods, 1- 5 days and 6-30 days

Time frame: Day 1-5 and Day 6-30

Number of Adverse Events (AEs) per participant

Number of AEs per individual

Time frame: Up to day 30

Change in Platelets count

Change in blood levels (Platelets) over 5 days following randomization and at day 30