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.

项目摘要败血症是一种医疗紧急事件，定义为由于宿主失调而导致的威胁生命的器官功能障碍对感染的反应。败血性休克是最严重的形式，涉及心血管衰竭。多于美国的75,000名儿童和全世界的400万儿童都有败血症或化粪池冲击住院年。败血症目前是美国最昂贵的医院病，对于重症患者，包括儿童 - 是多个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败血症的疗法33，因为流体复苏为化粪池提供了最佳的益处休克（抗生素除外），努力识别最有效的流体给药战略。尽管取得了进展，但幸存的败血症运动描述的知识剩余关键差距是哪种结晶液是最初用于初始复苏败血性休克的最有效和最安全的。两种类型的晶体用于败血症的复苏：0.9％“正常”盐水（NS）和均衡的液体（BF）。 BF在NS中具有完善的生物学和生理优势，发现了两项最近的成人试验 BF降低了主要的不良肾脏事件和死亡率。但是，在没有小儿特异的情况下数据，NS复苏仍然是小儿急诊临床医生的压倒性偏好。我们因此，建议败血症中平衡与正常盐水液的务实的儿科试验 Bolus）研究是一项随机，开放标签的务实比较有效性试验，以测试相对怀疑性败血性休克儿童中BF与NS液复苏的有效性和安全性。八小儿急诊应用研究网络（PECARN）的儿科急诊室将与加拿大，澳大利亚和新西兰的网站合作，注册8,800名涉嫌化味的儿童震惊。符合条件的患者将通过预期知情同意书或经过适当的道德保障措施，“知情同意书的例外”，以进行紧急研究。受试者将是随机的用NS或BF进行24-48小时的液体复苏和维护流体，以及其他各个方面由护理团队酌情决定的流体类型。我们的主要结果是其中的主要不良肾脏事件随机化30天（Make30），一个以患者为中心的复合终点，包括持续肾脏功能障碍，透析或死亡的启动。该结果解决了BF的生物学优势与NS相比，保持肾血流和功能。次要结果包括个人 Make30的组成部分，无医院日期，住院时间，90天死亡率和指定的安全活动。这项务实的审判将为“范式转变”提供确定的证据，以移动从0.9％盐水到败血性休克儿童的临床实践。