Clinical trial NCT05611710: Anakinra in Dengue With Hyperinflammation ( AnaDen )
Official title: Anakinra for Dengue Patients With Hyperinflammation - a Randomized Double-blind Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Dengue
Dengue With Warning Signs
Severe Dengue
Anakinra
Immuno-modulation
Anti-inflammatory Agents
Macrophage Activation Syndrome
Hyperinflammatory Syndrome
Cytokine Storm
Keywords: Dengue
Hyperinflammatory syndrome
Anakinra
Vietnam
Lead sponsor: Oxford University Clinical Research Unit, Vietnam
Sponsor class: OTHER
Collaborators: name: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
name: Wellcome Trust
First posted: 2022-11-10
Enrollment: 160
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This is a randomized, double blinded, placebo controlled trial of anakinra in patients with dengue with warning signs or severe dengue
Primary purpose: TREATMENT

Brief summary: 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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in modified Sequential Organ Failure Assessment score (mSOFA core, modified for limited resource settings and dengue) within 4 days
timeFrame: baseline, up to day 4
Secondary outcomes:
measure: Mortality
timeFrame: Up to day 30
measure: Change in modified Sequential Organ Failure Assessment score (mSOFA core, modified for limited resource settings and dengue) at day 7
timeFrame: baseline, day 7
measure: Number of days treated in Intensive care unit (ICU)
timeFrame: Up to day 30
measure: Number of days treated in hospital
timeFrame: Up to day 30
measure: Number of participants with Serious Adverse Events (SAEs)
timeFrame: Day 1-5 and Day 6-30
measure: Number of Adverse Events (AEs) per participant
timeFrame: Up to day 30
measure: Change in Platelets count
timeFrame: Up to day 5, at day 30
measure: Change in neutrophils count
timeFrame: Up to day 5, at day 30
measure: Change of ALT levels
timeFrame: Up to day 5, at day 30
measure: Change of Ferritin levels
timeFrame: Up to day 5, at day 30
measure: Change of CRP levels
timeFrame: Up to day 5, at day 30
measure: Time to normalization of blood levels
timeFrame: Up to day 30
measure: Platelet nadir
timeFrame: Up to day 30
measure: Fever clearance time
timeFrame: Up to day 30
measure: Duration of viraemia
timeFrame: Up to day 30
measure: Area under the curve (AUC) of the serial viral load measurements during hospital stay
timeFrame: at discharge (assessed up to day 8)
measure: Patients' quality of life questionnaire score
timeFrame: at discharge (assessed up to day 8) and at day 30
Other outcomes:
measure: Change in immune cells
timeFrame: Up to day 90
Locations:
city: Ho Chi Minh
country: Vietnam
facility: Hospital for Tropical Diseases
Study officials:
affiliation: University of Oxford, UK
name: Sophie Yacoub
role: PRINCIPAL_INVESTIGATOR
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