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

基本信息

批准号：
10663777
负责人：
MICHAEL SD AGUS
金额：
$ 172.3万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10663777
关键词：
Acute Address Admission activity Adrenal Cortex Hormones Adrenal gland hypofunction Adult Adverse event Algorithms Antibiotics Benefits and Risks Biological Markers Cessation of life Child Childhood Clinical Critically ill children Data Delirium Diagnosis Disease Double-Blind Method Electroconvulsive Therapy Enrollment Equipment and supply inventories Event Exhibits Extracorporeal Membrane Oxygenation Failure Family dynamics Functional disorder Funding Gastrointestinal Hemorrhage Gene Expression Genetic Transcription Glucocorticoids Guidelines Health Care Costs Health Expenditures Hospital Mortality Hospitalization 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 Placebo Control Placebos Public Health Quality of life Randomized Randomized, Controlled 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 biomarker performance biomarker validation clinical practice double-blind placebo controlled trial functional status health related quality of life hemodynamics improved innovation mortality mortality risk patient oriented pediatric sepsis prevent primary outcome prognostic prospective randomized, clinical trials secondary outcome treatment guidelines ventilation

项目摘要

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.

小儿败血性休克（SHIPS）项目摘要中的应力氢化可的松败血症代表了全世界儿童死亡率的最常见原因。在曼联仅州，每天都会诊断出200例儿科败血症病例目前，死亡率为5-10％，医疗保健支出每年接近50亿美元。此外，几乎有40％的儿童接受儿科重症监护病房（PICUS）败血症后一年的震惊尚未保持其基线健康相关的生活质量事件。在早期复兴儿童患有败血性休克的过程中，除了抗生素，体积最新的儿科治疗指南替换和血管活性 - 触发性支持建议从业者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失败。但是，潜在的好处并且尚未严格检查此建议的风险。一方面，皮质类固醇低廉，经常被证明可以改善败血症儿童和成人的血液动力学状态。相反，众所周知改变大约30％人类基因组的转录。值得注意的是，皮质类固醇会下降调节免疫响应的大多数方面，尤其是适应性免疫。而且，最近的数据表明，败血症中具有特定基因表达谱的儿童具有用皮质类固醇治疗死亡率的可能性增加。船舶（小儿败血性休克中的应力氢化可的松）是一种前瞻性，随机的，双盲，安慰剂对照试验，检查辅助的潜在益处和风险氢化可的松为患有液体和血管活性 - 触发性难治性的重症儿童开处方败血性冲击。在基线时，最多将招募，随机和评估1,032名儿童 PICU排放，研究入学/随机化后的28和90天。主要假设是，与安慰剂相比，氢化可的松将减少结果较差的受试者的比例，被定义为死亡或严重受损（≥25％）减少基线）与健康相关的生活质量。我们还将跟随受试者检测一侧治疗的影响。最后，我们将检验以下假设，即基于生物标志物的预后和预测性丰富策略可以提高我们确定哪些感染儿童的能力冲击更有可能受益于辅助氢化可的松，并且可能受到损害。这随机控制试验将对公共卫生产生重大影响迄今为止，缺少证据，以告知有关儿童败血性休克治疗的准则。