Anakinra in Dengue With Hyperinflammation ( AnaDen )
- Conditions
- Hyperinflammatory SyndromeMacrophage Activation SyndromeSevere DengueAnti-inflammatory AgentsDengueDengue With Warning SignsAnakinraImmuno-modulationCytokine Storm
- Interventions
- Drug: Placebo
- Registration Number
- NCT05611710
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 160
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Placebo Placebo The control group will be formed of 80 dengue patients with warning signs or severe dengue receiving placebo. Anakinra Anakinra The intervention group will include 80 dengue patients with warning signs or severe dengue receiving anakinra.
- Primary Outcome Measures
Name Time Method Change in modified Sequential Organ Failure Assessment score (mSOFA core, modified for limited resource settings and dengue) within 4 days baseline, up to day 4 Change in mSOFA score over 4 days after randomization (min score= 0, max score = 24, higher scores mean worse outcomes)
- Secondary Outcome Measures
Name Time Method Mortality Up to day 30 Number of death up to day 30
Change in Platelets count Up to day 5, at day 30 Change in blood levels (Platelets) over 5 days following randomization and at day 30
Change of ALT levels Up to day 5, at day 30 Change in blood levels (ALT) over 5 days following randomization and at day 30
Change of Ferritin levels Up to day 5, at day 30 Change in blood levels (Ferritin) over 5 days following randomization and at day 30
Fever clearance time Up to day 30 Time to temperature \<37.5 for at least 48 hours
Number of Adverse Events (AEs) per participant Up to day 30 Number of AEs per individual
Change of CRP levels Up to day 5, at day 30 Change in blood levels (CRP) over 5 days following randomization and at day 30
Area under the curve (AUC) of the serial viral load measurements during hospital stay at discharge (assessed up to day 8) AUC of viral load measurements during hospital stay will be reported
Number of days treated in hospital Up to day 30 Number of days treated in hospital
Number of participants with Serious Adverse Events (SAEs) Day 1-5 and Day 6-30 Number of participants having SAEs within 2 time-periods, 1- 5 days and 6-30 days
Change in neutrophils count Up to day 5, at day 30 Change in blood levels (neutrophils) over 5 days following randomization and at day 30
Time to normalization of blood levels Up to day 30 Time to normalization of platelets (defined as \>150 x109/l) and neutrophils (\>2 x109/l)
Duration of viraemia Up to day 30 Number of days from enrollment to the first undetectable viraemia (negative in qPCR and NS1)
Number of days treated in Intensive care unit (ICU) Up to day 30 Number of days treated in ICU
Platelet nadir Up to day 30 Lowest platelet count recorded during admission
Change in modified Sequential Organ Failure Assessment score (mSOFA core, modified for limited resource settings and dengue) at day 7 baseline, day 7 Change in mSOFA score at day 7 post randomization (min score= 0, max score = 24, higher scores mean worse outcomes)
Patients' quality of life questionnaire score at discharge (assessed up to day 8) and at day 30 Patients' quality of life during their hospitalisation will be explored at discharge and day 30 using the EQ-5D questionnaire.
Trial Locations
- Locations (1)
Hospital for Tropical Diseases
🇻🇳Ho Chi Minh, Vietnam