PRagMatic Pediatric Trial of Balanced versus NOrmaL Saline FlUid in Sepsis (PRoMPT BOLUS)

平衡与普通生理盐水治疗脓毒症的实用儿科试验（快速推注）

基本信息

批准号：
10261344
负责人：
Frances B Balamuth
金额：
$ 83.13万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-11 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10261344
关键词：
Accident and Emergency department Acute Acute Renal Failure with Renal Papillary Necrosis Address Adherence Adult Adverse event Affect Anions Antibiotics Applied Research Australia Biological Blood Coagulation Disorders Buffers Canada Cardiovascular system Caring Centers for Disease Control and Prevention (U.S.)Cessation of life Child Childhood Chlorides Clinical Collaborations Companions Critical Care Critical Illness Data Dialysis procedure Emergency Care Emergency Department Physician Emergency research Enrollment Equipoise Ethics Event Failure Feasibility Studies Follow-Up Studies Frequencies Functional disorder Funding Guidelines Hospital Mortality Hospitals Hour Immune System Diseases Immune response Individual Infection Informed Consent International Isotonic Exercise Kidney Knowledge Lactated Ringer&apos s Solution Length of Stay Life Liquid substance Literature Maintenance Medical emergency Monitor Multicenter Trials Multiple Organ Failure New Zealand Normal saline Organ Outcome Patients Personal Communication Physicians Physiological Pilot Projects Population Provider Public Health Randomized Registries Relative Risks Renal Blood Flow Reporting Research Design Resuscitation Risk Reduction Safety Saline Sample Size Sepsis Septic Shock Shock Site Specific qualifier value Surveys Testing Therapeutic Translational Research United States World Health Organization base clinical practice comparative effectiveness comparative effectiveness trial cost cost efficient crystalloid day length improved innovation kidney dysfunction mortality open label patient oriented pediatric emergency pragmatic trial preference preservation primary outcome prospective randomized trial relative effectiveness secondary outcome treatment optimization

项目摘要

Project Summary Sepsis is a medical emergency defined as life-threatening organ dysfunction due to a dysregulated host response to infection. Septic shock is the most severe form, involving cardiovascular failure. More than 75,000 children in the US and four million children worldwide are hospitalized with sepsis or septic shock every year. Sepsis is currently the most expensive hospital condition in the US and, for critically ill patients— including children—is the most common cause of multiple organ dysfunction syndrome and hospital death.1,26 The World Health Organization and the US Centers for Disease Control and Prevention have called for optimizing therapies for sepsis.33 Because fluid resuscitation provides the best established benefit for septic shock (other than antibiotics), there has been an effort to identify the most effective fluid administration strategy. Despite progress, a remaining key gap in knowledge delineated by the Surviving Sepsis Campaign is which crystalloid fluid is the most effective and safest to use for initial resuscitation of septic shock. Two types of crystalloids are used for resuscitation in sepsis: 0.9% “normal” saline (NS) and balanced fluids (BF). BF have well-established biologic and physiologic advantages over NS and two recent adult trials found that BF reduced major adverse kidney events and mortality. However, in the absence of pediatric-specific data, NS resuscitation remains the overwhelming preference among pediatric emergency clinicians. We therefore propose the PRagMatic Pediatric Trial of Balanced versus NOrmaL Saline FlUid in Sepsis (PRoMPT BOLUS) study, a randomized, open-label, pragmatic comparative effectiveness trial, to test the relative effectiveness and safety of BF versus NS fluid resuscitation in children with suspected septic shock. Eighteen pediatric emergency departments in the Pediatric Emergency Care Applied Research Network (PECARN) will collaborate with sites in Canada, Australia, and New Zealand to enroll 8,800 children with suspected septic shock. Eligible patients will be enrolled either through prospective informed consent or, after appropriate ethical safeguards, “Exception From Informed Consent” for emergency research. Subjects will be randomized to fluid resuscitation and maintenance fluids with either NS or BF for 24-48 hours, with all aspects of care other than fluid type at the discretion of the care team. Our primary outcome is major adverse kidney events within 30 days from randomization (MAKE30), a patient-centered composite endpoint that includes persistent kidney dysfunction, initiation of dialysis, or death. This outcome addresses the biological advantages of BF to preserve renal blood flow and function compared to NS. Secondary outcomes include the individual components of MAKE30, hospital-free days, length of stay, 90-day mortality, and specified safety events. This pragmatic trial will provide the definitive evidence necessary for a “paradigm shift” to move clinical practice from 0.9% saline to balanced fluid-based resuscitation in children with septic shock.

项目概要败血症是一种医疗紧急情况，定义为由于宿主失调而导致危及生命的器官功能障碍对感染的反应是最严重的形式，涉及心血管衰竭。美国每年有 75,000 名儿童和全球 400 万儿童因败血症或败血性休克住院治疗今年，败血症是美国目前最昂贵的医院疾病，对于重症患者来说—— 包括儿童——是多器官功能障碍综合征和医院死亡的最常见原因。1,26 世界卫生组织和美国疾病控制与预防中心呼吁优化脓毒症的治疗方法。33 因为液体复苏为脓毒症提供了最佳的既定益处休克（抗生素除外），一直在努力确定最有效的输液方法尽管取得了进展，但“拯救脓毒症运动”所描绘的知识仍然存在关键差距。哪种晶体液用于感染性休克的初始复苏最有效且最安全。两种类型的晶体用于脓毒症复苏：0.9%“生理”盐水 (NS) 和平衡液 (BF) 与 NS 相比，BF 具有明确的生物学和生理学优势，最近的两项成人试验发现。然而，在缺乏儿科特异性的情况下，BF 减少了主要的肾脏不良事件和死亡率。数据显示，NS 复苏仍然是儿科急诊人群的压倒性偏好。因此，建议进行平衡与普通生理盐水治疗脓毒症的实用儿科试验（PRoMPT） BOLUS）研究，一项随机、开放标签、务实的比较有效性试验，旨在测试相对 BF 与 NS 液体复苏在疑似感染性休克儿童中的有效性和安全性 18。儿科急诊应用研究网络 (PECARN) 的儿科急诊科将与加拿大、澳大利亚和新西兰的机构合作，招募 8,800 名疑似败血症儿童符合条件的患者将通过前瞻性知情同意或在适当的情况下入组。道德保障，紧急研究的“知情同意例外”受试者将被随机化。使用 NS 或 BF 进行液体复苏和维持液体 24-48 小时，以及其他各方面的护理我们的主要结局是由护理团队决定的液体类型。随机化后 30 天 (MAKE30)，一个以患者为中心的复合终点，包括持续性肾病该结果体现了 BF 的生物学优势。与 NS 相比，保留肾血流量和功能次要结果包括个体。 MAKE30 的组成部分、无住院天数、住院时间、90 天死亡率和特定安全事件。这项务实的试验将为推动“范式转变”提供必要的明确证据感染性休克儿童从 0.9% 生理盐水到平衡液体复苏的临床实践。