Protocolized Goal-directed Resuscitation of Septic Shock to Prevent AKI

脓毒性休克的目标导向复苏方案以预防 AKI

• 批准号: 8486422
• 负责人: John A Kellum
• 金额: $ 57.45万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-15 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8486422
• 关键词: Acute Renal Failure with Renal Papillary Necrosis; Address; Affect; American; Ancillary Study; Biological Markers; Blood; Caring; Central venous pressure; Chronic Kidney Failure; Clinical; Clinical Research; Coagulation Process; Cohort Studies; Critical Illness; Development; Effectiveness; Enrollment; Erythrocytes; Functional disorder; Funding; Future; Goals; Home visitation; Hospitals; House Call; Hypotension; IV Fluid; Immune response; Impairment; Incidence; Infection; Inflammation; Inflammatory; Injury; Injury to Kidney; Interleukin-18; Intervention; Ischemia; Kidney; Laboratories; Liquid substance; Modeling; Monitor; Multicenter Trials; National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; Natural History; Nephrotoxic; Organ; Outcome; Oxidative Stress; Parents; Pathway interactions; Patients; Population; Prevention; Protocols documentation; Randomized; Recording of previous events; Recovery; Reporting; Resolution; Resuscitation; Risk; Rivers; Sepsis; Septic Shock; Serum Markers; Severities; Staging; Survivors; Syndrome; TNFRSF5 gene; Testing; Therapeutic; Therapy Clinical Trials; Thrombosis; Time; United States National Institutes of Health; Urine; Vasoconstrictor Agents; Venous; Work; arm; attenuation; clinical risk; cohort; common treatment; cost; follow-up; hemodynamics; improved; injury and repair; intervention effect; outcome forecast; patient population; post gamma-globulins; pressure; prevent; public health relevance; research study; response; standard care; treatment as usual; urinary; vasoactive agent

DESCRIPTION (provided by applicant): Under PAR-07-024, Ancillary Studies to Major Ongoing NIDDK and NHLBI Clinical Research Studies NIDDK, we are proposing to conduct a study which aims to examine the natural history of Acute Kidney Injury (AKI) arising in patients with sepsis. Sepsis is found in more than 50% of critically-ill patients with AKI.3 The NIH has recently funded a large therapeutic trial of early septic shock (P50 GM076659). This trial, Protocolized Care for Early Septic Shock (ProCESS), will randomize 1935 patients at 19 centers to three different treatment arms. The opportunity to study patients from the ProCESS cohort presents us with an historic opportunity to prospectively conduct a large natural history study ancillary to an extensive multi-center trial in a setting which is most likely to result in AKI. Our proposal, Protocolized Goal-directed Resuscitation of Septic Shock to Prevent Acute Kidney Injury (ProGReSS AKI), will examine the effect of protocolized resuscitation on the development of AKI. We also seek to explore mechanisms underlying the effect of the intervention and to evaluate markers of renal injury and repair in order to help select patients for future interventional trials. In keeping with the NIH roadmap, in order to understand the clinical utility of this work, we will build a clinical risk prediction model that will consider biomarkers and clinical variables. We have organized these tasks as three specific aims: 1. test the hypothesis that protocolized resuscitation prevents or lessens severity or duration of AKI, 2. determine which pathophysiologic derangements (inflammation, ischemia, oxidative stress, and coagulation/ thrombosis), in combination or individually, are associated with the development of AKI, and 3. determine whether biomarkers can predict AKI and recovery from AKI in the setting of sepsis. Part of our study will include home visits, for which we have opted to separate from the parent trial so as to avoid any loss of enrollment incurred by the ancillary study. We will re-contact ProCESS subjects after discharge from the hospital and follow them at five time points for three years. Through this part of the study, we will determine if protocolized resuscitation is more effective in improving long term outcomes (survival, renal recovery, reduced progression of CKD) in the entire cohort as well as in the subpopulation that has evidence of AKI by biomarkers (biomarker-positive AKI).

描述（由申请方提供）：根据PAR-07-024，正在进行的主要NIDDK和NHLBI临床研究NIDDK的辅助研究，我们提议进行一项旨在检查脓毒症患者发生的急性肾损伤（阿基）自然史的研究。在超过50%的AKI危重患者中发现脓毒症。3 NIH最近资助了一项早期脓毒性休克的大型治疗试验（P50 GM 076659）。这项试验，早期感染性休克的方案化护理（ProCESS），将19个中心的1935例患者随机分配到3个不同的治疗组。对来自ProCESS队列的患者进行研究的机会为我们提供了一个历史性的机会，可以在最有可能导致阿基的环境中前瞻性地进行一项大型自然史研究，以辅助一项广泛的多中心试验。我们的提案，即预防急性肾损伤的感染性休克协议化目标导向复苏（ProGReSS阿基），将检查协议化复苏对阿基发展的影响。我们还试图探索干预效果的机制，并评估肾损伤和修复的标志物，以帮助选择患者进行未来的干预试验。为了与NIH路线图保持一致，为了了解这项工作的临床效用，我们将建立一个考虑生物标志物和临床变量的临床风险预测模型。我们将这些任务分为三个具体目标：1.检验协议复苏预防或减轻阿基的严重程度或持续时间的假设，2.确定哪些病理生理紊乱（炎症、缺血、氧化应激和凝血/血栓形成）组合或单独地与阿基的发展相关，以及3.确定生物标志物是否可以预测脓毒症背景下的阿基和阿基恢复。我们的部分研究将包括家庭访视，我们选择将其与母试验分开，以避免辅助研究导致的任何入组损失。我们将在出院后重新联系ProCESS受试者，并在五个时间点对他们进行为期三年的随访。通过这部分研究，我们将确定方案复苏是否能更有效地改善整个队列以及通过生物标志物（生物标志物阳性阿基）证明阿基的亚群的长期结局（生存期、肾脏恢复、CKD进展减缓）。