SHIPSS: Stress Hydrocortisone In Pediatric Septic Shock

SHIPSS：应激性氢化可的松治疗小儿感染性休克

• 批准号: 9764560
• 负责人: MICHAEL SD AGUS
• 金额: $ 189.35万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9764560
• 关键词: Acute; Address; Adrenal Cortex Hormones; Adrenal gland hypofunction; Adult; Adverse event; Algorithms; Antibiotics; Benefits and Risks; Biological Markers; Cessation of life; Child; Childhood; Clinical; Conflict (Psychology); Critically ill children; Data; Delirium; Diagnosis; Disease; Double-Blind Method; Electroconvulsive Therapy; Enrollment; Environmental air flow; Equipment and supply inventories; Event; Exhibits; Expression Profiling; Extracorporeal Membrane Oxygenation; Failure; Family dynamics; Functional disorder; Funding; Gastrointestinal Hemorrhage; Gene Expression; Genetic Transcription; Glucocorticoids; Guidelines; Health Care Costs; Health Expenditures; Hospital Mortality; Hospitals; Human Genome; Hydrocortisone; Hyperglycemia; Immune response; Impairment; Infusion procedures; Institution; Intervention; Intervention Trial; Knowledge; Liquid substance; Meta-Analysis; Modeling; Multiple Organ Failure; Neonatal; Nosocomial Infections; Organ; Outcome; Outcome Measure; Parents; Pathogenesis; Patients; Pediatric Intensive Care Units; Pharmaceutical Preparations; Pituitary-Adrenal System; Placebos; Public Health; Quality of life; Randomized; Randomized Clinical Trials; Recommendation; Refractory; Renal Replacement Therapy; Reporting; Research; Resources; Resuscitation; Risk; Sepsis; Septic Shock; Severity of illness; Specific qualifier value; Stress; Subgroup; Testing; Therapeutic Intervention; Time; Treatment Side Effects; United States; adaptive immunity; base; biomarker performance; clinical practice; control trial; double-blind placebo controlled trial; functional status; health related quality of life; hemodynamics; improved; innovation; mortality; mortality risk; patient oriented; prevent; primary outcome; prognostic; prospective; secondary outcome; treatment guidelines

Stress Hydrocortisone In Pediatric Septic Shock (SHIPSS) Project Summary Sepsis represents the most common cause of childhood mortality worldwide. In the United States alone, 200 cases of pediatric sepsis are diagnosed each day, with an associated hospital mortality rate of 5-10% and health care expenditures now approaching $5 billion annually. Moreover, nearly 40% of children admitted to pediatric intensive care units (PICUs) for septic shock have not regained their baseline health-related quality of life one year following the sepsis event. During early resuscitation of the child with septic shock, in addition to antibiotics, volume replacement, and vasoactive-inotropic support, the most recent pediatric treatment guidelines advise the practitioner to consider adjunctive hydrocortisone therapy if the patient “is at risk of absolute adrenal insufficiency or adrenal pituitary axis failure”. However, the potential benefits and risks of this recommendation have not been rigorously examined. On the one hand, corticosteroids are inexpensive and have been frequently demonstrated to improve hemodynamic status in children and adults with sepsis. Conversely, this drug class is known to alter transcription of approximately 30% of the human genome. Notably, corticosteroids down regulate most aspects of the immune response, but particularly adaptive immunity. Moreover, recent data suggests that children with particular gene expression profiles in sepsis have increased likelihood of mortality when treated with corticosteroids. SHIPSS (Stress Hydrocortisone In Pediatric Septic Shock) is a prospective, randomized, double-blinded, placebo-controlled trial examining the potential benefits and risks of adjunctive hydrocortisone prescribed to critically ill children with fluid and vasoactive-inotropic refractory septic shock. Up to 1,032 children will be enrolled, randomized, and evaluated at baseline, PICU discharge, and 28 and 90 days following study enrollment/randomization. The primary hypothesis is that hydrocortisone, compared to placebo, will decrease the proportion of subjects with poor outcomes, defined as death or severely impaired (≥25% decrease from baseline) health-related quality of life. We will also follow subjects to detect side effects of the treatment. Finally, we will test the hypothesis that biomarker-based prognostic and predictive enrichment strategies can improve our ability to identify which children with septic shock are more likely to benefit from adjunctive hydrocortisone, and which may be harmed. This randomized control trial will have a significant impact on public health by providing the heretofore missing evidence to inform guidelines regarding therapy for septic shock in children.

应激性氢化可的松治疗小儿感染性休克(SHIPSS)项目总结 败血症是全世界儿童死亡的最常见原因。在美国 仅在美国，一家附属医院每天就诊断出200例儿童脓毒症。 死亡率为5%-10%，医疗保健支出现在每年接近50亿美元。 此外，近40%的儿童因败血症而住进儿科重症监护病房(PICU) 脓毒症后一年，休克仍未恢复与健康相关的基线生活质量 事件。 在感染性休克患儿的早期复苏过程中，除使用抗生素外，还要增加容量 替代和血管活性肌力支持，这是最新的儿科治疗指南 建议医生考虑辅助氢化可的松治疗，如果患者“有 绝对肾上腺功能不全或肾上腺垂体轴衰竭“。然而，潜在的好处是 而且这一建议的风险还没有得到严格的审查。一方面， 皮质类固醇价格低廉，经常被证明可以改善病情。 脓毒症儿童和成人的血流动力学状态。相反，这类药物已知为 改变大约30%的人类基因组的转录。值得注意的是，皮质类固醇激素下降 调节免疫反应的大部分方面，尤其是适应性免疫。此外， 最近的数据表明，在脓毒症中有特殊基因表达谱的儿童 当使用皮质类固醇治疗时，死亡率增加。 SHIPSS(应激性氢化可的松治疗小儿感染性休克)是一种前瞻性、随机、 双盲、安慰剂对照试验，检查辅助剂的潜在益处和风险 氢化可的松用于液体和血管活性变力难治性危重患儿 感染性休克。多达1,032名儿童将在基线水平上进行登记、随机和评估， PICU出院，以及研究登记/随机分组后28天和90天。 主要的假设是，与安慰剂相比，氢化可的松将降低 预后不佳的受试者比例，定义为死亡或严重受损(≥25% 从基线开始下降)与健康相关的生活质量。我们也会跟随受试者去侦测侧面 治疗效果。最后，我们将检验基于生物标记物的预后和 预见性充实策略可以提高我们识别哪些儿童患有败血症的能力 休克更有可能从辅助性氢化可的松中受益，而氢化可的松可能会受到伤害。这 随机对照试验将通过提供 到目前为止，缺乏证据来指导儿童感染性休克的治疗。