Anakinra for Dengue Patients With Hyperinflammation - a Randomized Double-blind Placebo-controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Change in modified Sequential Organ Failure Assessment score (mSOFA core, modified for limited resource settings and dengue) within 4 days
研究概览
简要总结
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
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Double blinded
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Placebo
The control group will be formed of 80 dengue patients with warning signs or severe dengue receiving placebo.
干预措施: Placebo (Drug)
Anakinra
The intervention group will include 80 dengue patients with warning signs or severe dengue receiving anakinra.
干预措施: Anakinra (Drug)
结局指标
主要结局
Change in modified Sequential Organ Failure Assessment score (mSOFA core, modified for limited resource settings and dengue) within 4 days
时间窗: 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)
次要结局
- Mortality(Up to day 30)
- Change in Platelets count(Up to day 5, at day 30)
- Change of ALT levels(Up to day 5, at day 30)
- Change of Ferritin levels(Up to day 5, at day 30)
- Fever clearance time(Up to day 30)
- Change of CRP levels(Up to day 5, at day 30)
- Area under the curve (AUC) of the serial viral load measurements during hospital stay(at discharge (assessed up to day 8))
- Number of days treated in hospital(Up to day 30)
- Number of participants with Serious Adverse Events (SAEs)(Day 1-5 and Day 6-30)
- Change in neutrophils count(Up to day 5, at day 30)
- Time to normalization of blood levels(Up to day 30)
- Duration of viraemia(Up to day 30)
- Number of days treated in Intensive care unit (ICU)(Up to day 30)
- Platelet nadir(Up to day 30)
- Change in modified Sequential Organ Failure Assessment score (mSOFA core, modified for limited resource settings and dengue) at day 7(baseline, day 7)
- Number of Adverse Events (AEs) per participant(Up to day 30)
- Patients' quality of life questionnaire score(at discharge (assessed up to day 8) and at day 30)