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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.

应激性氢化可的松治疗小儿感染性休克 (SHIPSS) 项目摘要败血症是全世界儿童死亡的最常见原因。在美国仅各州一家相关医院每天就诊断出 200 例小儿败血症病例死亡率为 5-10%，每年医疗保健支出接近 50 亿美元。此外，近 40% 的儿童因化脓性肺炎入住儿科重症监护病房 (PICU) 败血症一年后休克尚未恢复与健康相关的生活质量基线事件。在感染性休克儿童的早期复苏过程中，除了抗生素外，替代疗法和血管活性肌力支持是最新的儿科治疗指南如果患者“有以下风险”，建议医生考虑辅助氢化可的松治疗绝对肾上腺功能不全或肾上腺垂体轴衰竭“。然而，潜在的好处该建议的风险尚未经过严格审查。一方面，皮质类固醇价格便宜，并且经常被证明可以改善脓毒症儿童和成人的血流动力学状态。相反，已知该药物类别改变人类基因组约 30% 的转录。值得注意的是，皮质类固醇下降调节免疫反应的大部分方面，尤其是适应性免疫。而且，最近的数据表明，患有脓毒症的具有特定基因表达谱的儿童使用皮质类固醇治疗时死亡的可能性增加。 SHIPSS（小儿败血性休克中的应激氢化可的松）是一项前瞻性、随机、双盲、安慰剂对照试验，检验辅助治疗的潜在益处和风险氢化可的松用于治疗液体和血管活性肌力难治性危重儿童败血性休克。多达 1,032 名儿童将被纳入、随机分组并进行基线评估， PICU 出院，以及研究入组/随机分组后 28 和 90 天。主要假设是，与安慰剂相比，氢化可的松会降低结局不佳（定义为死亡或严重受损）的受试者比例（≥25% 从基线下降）健康相关的生活质量。我们也会跟踪受试者来检测侧面治疗的效果。最后，我们将检验以下假设：基于生物标志物的预后和预测丰富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受益于氢化可的松的辅助治疗，而这可能会受到损害。这随机对照试验将通过提供以下内容对公共卫生产生重大影响：迄今为止，缺乏证据来指导有关儿童感染性休克治疗的指南。