GM-CSF for Reversal of Immunoparalysis in Pediatric Sepsis-induced MODS
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 141
- 试验地点
- 25
- 主要终点
- Cumulative 28-day Pediatric Logistic Organ Dysfunction (PELOD)-2 score
研究概览
简要总结
The GRACE-2 study is a prospective, multi-center, double-blind, randomized controlled trial of the drug GM-CSF vs placebo in children with sepsis-induced multiple organ dysfunction syndrome (MODS) who have immunoparalysis with mild to moderate inflammation.
详细描述
The GRACE-2 study is a is a prospective, multi-center, double-blind, randomized controlled trial of the drug GM-CSF vs placebo in children with sepsis-induced multiple organ dysfunction syndrome (MODS) who have immunoparalysis with mild to moderate inflammation. Eligible subjects will undergo centralized immunophenotyping on MODS Day 2. Those who are found to have immunoparalysis (a whole blood LPS-induced TNF-alpha production capacity < 200 pg/ml) with mild to moderate inflammation (serum ferritin level < 2000 ng/ml) will be randomized to receive intravenous (IV) GM-CSF at a dose of 125 mcg/m2/day x 7 days or placebo. The primary outcome variable is the cumulative 28-day Pediatric Logistic Organ Dysfunction (PELOD)-2 score. Secondary outcomes include measures of health-related quality of life and function status at 3 months from randomization.
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
- •History of myeloid leukemia, myelodysplasia, or autoimmune thrombocytopenia; 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 GM-CSF; OR
- •Known pregnancy; OR
- •Lactating females; OR
- •Receipt of anakinra or GM-CSF within the previous 28 days; OR
- •Resolution of MODS by MODS Day 2; OR
- •Previous enrollment in the GRACE-2 study.
研究组 & 干预措施
GM-CSF
Intravenous GM-CSF 125 mcg/m2/day x 7 days
干预措施: GM-CSF (Drug)
Placebo
Intravenous placebo x 7 days
干预措施: Placebo (Other)
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
Cumulative Pediatric Logistic Organ Dysfunction (PELOD)-2 score through 28 days post-randomization. The range of PELOD-2 score for a given day is 0 - 33 with a higher number being worse.
次要结局
- 3-month health-related quality of life(3 months post-randomization)
- 3-month functional status(3 months post-randomization)
研究者
Mark Hall
Chief, Critical Care Medicine
Nationwide Children's Hospital