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）

• 批准号: 10477384
• 负责人: Frances B Balamuth
• 金额: $ 83.22万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 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/10477384
• 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' s Solution; Length of Stay; Life; Liquid substance; Literature; Maintenance; Medical emergency; Monitor; Multicenter Trials; Multiple Organ Failure; National Center for Advancing Translational Sciences; 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; 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; pediatric sepsis; pragmatic trial; preference; preservation; primary outcome; prospective; randomized trial; relative effectiveness; secondary outcome; treatment optimization

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。感染性休克是最严重的形式，涉及心血管衰竭。多于 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 年。脓毒症目前是美国最昂贵的医院疾病，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 战略。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）。 BF 相对于 NS 具有公认的生物学和生理学优势，最近的两项成人试验发现 BF 减少了主要的肾脏不良事件和死亡率。然而，在缺乏儿科特异性的情况下 数据显示，NS 复苏仍然是儿科急诊临床医生的压倒性偏好。我们 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。十八 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 震惊。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”。受试者将被随机分配 使用 NS 或 BF 进行液体复苏和维持液体 24-48 小时，并进行各方面的护理 液体类型由护理团队自行决定。我们的主要结局是体内主要的肾脏不良事件 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 功能障碍、开始透析或死亡。这一结果体现了 BF 的生物学优势 与 NS 相比，可以保留肾血流量和功能。次要结果包括个人 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。