Protocolized Goal-directed Resuscitation of Septic Shock to Prevent AKI (ProGReSS

脓毒性休克的目标导向复苏方案以预防 AKI (ProGReSS

• 批准号: 7884826
• 负责人: John A Kellum
• 金额: $ 76.67万
• 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 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7884826
• 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; Rifles; 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; 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). PUBLIC HEALTH RELEVANCE: The incidence of acute kidney injury (AKI) is estimated at approximately 2000 per million population. This study will examine the effectiveness of the most common treatment (fluids) for the prevention and/or attenuation of AKI resulting from its most common cause (sepsis). To guide future studies, this project will also determine which pathophysiologic derangements are associated with the development of AKI, and determine whether currently available biomarkers can predict AKI and recovery from AKI in the setting of sepsis.

描述（由申请人提供）：根据 PAR-07-024，主要正在进行的 NIDDK 和 NHLBI 临床研究的辅助研究 NIDDK，我们建议进行一项研究，旨在检查以下疾病引起的急性肾损伤 (AKI) 的自然史：败血症患者。超过 50% 的 AKI 危重患者患有败血症。3 NIH 最近资助了一项早期败血性休克的大型治疗试验 (P50 GM076659)。这项名为早期感染性休克治疗方案 (ProCESS) 的试验将把 19 个中心的 1935 名患者随机分配到三个不同的治疗组。对 ProCESS 队列中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 AKI 的环境中前瞻性地进行一项大型自然史研究，辅助进行广泛的多中心试验。我们的提案“脓毒性休克目标导向复苏方案预防急性肾损伤 (ProGReSS AKI)”将研究方案复苏对 AKI 发展的影响。我们还寻求探索干预效果的潜在机制，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。根据 NIH 路线图，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. 检验方案复苏可预防或减轻 AKI 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 AKI 的发展相关，并且 3. 确定生物标志物是否可以预测脓毒症情况下的 AKI 和 AKI 的恢复。我们研究的一部分将包括家访，为此我们选择与家长试验分开，以避免辅助研究造成的任何入学损失。我们将在出院后重新联系 ProCESS 受试者，并在三年内的五个时间点对他们进行跟踪。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生物标志物显示 AKI 证据的亚群的长期结局（生存、肾脏恢复、CKD 进展减缓）。生物标志物阳性 AKI）。 公共卫生相关性：急性肾损伤 (AKI) 的发病率估计约为每百万人口 2000 人。本研究将探讨最常见的治疗方法（液体）对于预防和/或减轻由最常见原因（脓毒症）引起的 AKI 的有效性。为了指导未来的研究，该项目还将确定哪些病理生理紊乱与 AKI 的发生相关，并确定当前可用的生物标志物是否可以预测脓毒症情况下的 AKI 和 AKI 的恢复。