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: 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
• 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' 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

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 脓毒症是一种医疗急症，定义为由于宿主调节失调而导致的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。多过 美国每年有7.5万名儿童和全球400万名儿童因败血症或感染性休克住院 年。脓毒症目前是美国最昂贵的医院疾病，对于危重患者来说- 包括儿童--是导致多器官功能障碍综合症和医院死亡的最常见原因。 世界卫生组织和美国疾病控制和预防中心呼吁 优化败血症的治疗。33因为液体复苏为败血症提供了最好的既定益处 休克(抗生素除外)，一直在努力确定最有效的液体给药 策略。尽管取得了进展，但幸存的脓毒症运动描绘出的知识方面的一个关键差距是 对于感染性休克的初始复苏，使用哪种晶体液体是最有效和最安全的。 败血症复苏使用两种晶体：0.9%生理盐水(NS)和平衡液 (BF)。BF与NS和最近的两项成人试验相比具有公认的生物学和生理学优势 BF减少了主要的不良肾脏事件和死亡率。然而，在缺乏儿科专科的情况下 数据显示，NS复苏仍然是儿科急诊医生的压倒性偏好。我们 因此提出了平衡盐水与正常盐水治疗败血症的实用儿科试验(PROMPT Bolus)研究，一项随机的、开放标签的、务实的比较有效性试验，以测试相对 BF与NS液体复苏对疑似感染性休克儿童的有效性和安全性。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网站合作，招募8800名疑似败血症儿童 令人震惊。符合条件的患者将通过预期知情同意或在适当的情况下进行登记 伦理保障，紧急研究的“知情同意例外”。受试者将被随机化 使用生理盐水或BF进行24-48小时的液体复苏和维持液，以及其他所有方面的护理 而不是液体类型，由护理团队自行决定。我们的主要结果是发生严重的肾脏不良事件 30天后随机化(MAKE30)，这是一个以患者为中心的复合终点，包括永久性肾脏 功能障碍、开始透析或死亡。这一结果解决了BF的生物学优势 与生理盐水相比，保存肾血流量和肾功能。次要结果包括个人 MAKE30的组成部分、无住院天数、住院时间、90天死亡率和指定的安全事件。 这一务实的试验将提供“范式转变”推进所需的确凿证据 感染性休克患儿从0.9%生理盐水到平衡液体复苏的临床实践。