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（由申请人提供）：根据PAR-07-024，对正在进行的NIDDK和NHLBI临床研究研究NIDDK进行的辅助研究NIDDK，我们提议进行一项研究，旨在研究sepsis患者急性肾脏损伤（AKI）的自然历史。在超过50％的AKI患者中发现了败血症。3NIH最近资助了早期败血性休克的大型治疗试验（P50 GM076659）。这项试验是对早期败血性休克（过程）的方案护理，将在1935年中心将1935例患者随机，至三个不同的治疗臂。从该过程中研究患者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AKI的环境中进行广泛的多中心试验进行大规模的自然历史研究。我们的提案，方案实现的败血性休克的目标复苏以防止急性肾脏损伤（AKI），将检查协议复苏对AKI发展的影响。我们还寻求探索干预效果的基础机制，并评估肾脏损伤和修复的标志物，以帮助选择患者以后的介入试验。为了与NIH路线图保持一致，为了了解这项工作的临床实用性，我们将建立一个临床风险预测模型，该模型将考虑生物标志物和临床变量。我们已经将这些任务组织为三个特定的目的：1。测试协议复苏的假设可预防或减少AKI的严重程度或持续时间，2。确定哪些病理生理危险（炎症，缺血，缺血，氧化压力，氧化压力，氧化压力和凝结/凝结/凝结剂），结合或单独地与AKI的发展相关。败血症的设置。我们研究的一部分将包括家庭访问，我们选择与父母试验分开，以免辅助研究造成的任何入学损失。从医院出院后，我们将重新接触过程受试者，并在五个时间点关注三年。通过这一研究，我们将确定整个队列中的方案复苏是否更有效地改善了长期结果（生存，肾脏恢复，CKD的降低）以及在亚种群中具有生物标志物（生物标志物-prosentive Aki）的AKI证据。