Targeted Reversal of Inflammation in Pediatric Sepsis-induced MODS (TRIPS)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 500
- 试验地点
- 60
- 主要终点
- Cumulative 28-day Pediatric Logistic Organ Dysfunction (PELOD-2) score
研究概览
简要总结
The TRIPS study is a prospective, multi-center, double-blind, adaptively randomized, placebo-controlled clinical trial of the drug anakinra for reversal of moderate to severe hyperinflammation in children with sepsis-induced multiple organ dysfunction syndrome (MODS).
详细描述
The TRIPS study is a prospective, multi-center, double-blind, adaptively randomized, placebo-controlled clinical trial of the drug anakinra for reversal of moderate to severe hyperinflammation in children with sepsis-induced multiple organ dysfunction syndrome (MODS). Eligible subjects will undergo centralized immunophenotyping on day 2 of MODS. Subjects without immunoparalysis (a whole blood ex vivo LPS-induced TNF-alpha production capacity < 200 pg/ml) and a serum ferritin level of 500 - 2,000 ng/ml or a serum C-reactive protein (CRP) ≥ 4 mg/dl will be eligible for randomization, along with subjects with a serum ferritin level of 2,000 - 10,000 ng/ml regardless of their TNF-alpha response. Eligible subjects will receive intravenous (IV) anakinra at a dose of 4, 8, 12, or 16 mg/kg/day or placebo for 7 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 1 Day 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥ 40 weeks corrected gestational age to < 18 years; AND
- •Admission to the PICU or CICU; AND
- •Onset of ≥ 2 new organ dysfunctions within the last 3 calendar days (compared to pre-sepsis baseline) as measured by the modified Proulx criteria; AND
- •Documented or suspected infection as the MODS inciting event.
排除标准
- •Weight <3kg; OR
- •Limitation of care order at the time of screening; OR
- •Patients at high likelihood of progression to brain death in opinion of the clinical team; OR
- •Moribund condition in which the patient is unlikely to survive the next 48 hours in opinion of the clinical team; OR
- •Current or prior diagnosis of hemophagocytic lymphohistiocytosis or macrophage activation syndrome; OR
- •Peripheral white blood cell count < 1,000 cells/mm3 as the result of myeloablative therapy OR receipt of myeloablative therapy within the previous 14 days; OR
- •Known allergy to anakinra, or E. coli-derived products; OR
- •Known pregnancy; OR
- •Lactating females; OR
- •Receipt of anakinra within the previous 28 days; OR
- •Resolution of MODS by MODS Day 2; OR
- •Previous enrollment in the TRIPS study.
研究组 & 干预措施
Anakinra 4 mg/kg/day
IV Anakinra 4mg/kg/day x 7 days
干预措施: Anakinra (Drug)
Anakinra 8 mg/kg/day
IV Anakinra 8 mg/kg/day x 7 days
干预措施: Anakinra (Drug)
Anakinra 12 mg/kg/day
IV Anakinra 12 mg/kg/day x 7 days
干预措施: Anakinra (Drug)
Anakinra 16 mg/kg/day
IV Anakinra 16 mg/kg/day x 7 days
干预措施: Anakinra (Drug)
Placebo
IV placebo x 7 days
干预措施: Placebo (Drug)
结局指标
主要结局
Cumulative 28-day Pediatric Logistic Organ Dysfunction (PELOD-2) score
时间窗: 28 days from randomization
The cumulative Pediatric Logistic Organ Dysfunction (PELOD)-2 score over 28 days from randomization. The range of daily PELOD-2 scores is from 0 - 33, with higher scores representing worse organ function.
次要结局
- 3-month functional status(3 months post-randomization)
- 3-month health-related quality of life(3 months post-randomization)
研究者
Mark Hall
Chief, Division of Critical Care Medicine
Nationwide Children's Hospital