HALF-PINT: Heart and Lung Failure - Pediatric INsulin Titration trial - CCC

半品脱：心肺衰竭 - 儿科胰岛素滴定试验 - CCC

• 批准号: 9111467
• 负责人: MICHAEL SD AGUS
• 金额: $ 8.25万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9111467
• 关键词: Acute; Acute Lung Injury; Adult; Advocate; Age; Algorithms; Behavioral; Blood Circulation; Blood Glucose; Brain; Calories; Cardiovascular system; Cause of Death; Child; Child Behavior Checklist; Childhood; Clinical Trials; Complication; Consensus; Control Groups; Critical Care; Critical Illness; Critically ill children; Data; Development; Diagnosis; Equipment and supply inventories; Failure; Functional disorder; Glucose; Heart; Hospital Mortality; Hour; Hyperglycemia; Hypoglycemia; Incidence; Infant; Infusion procedures; Insulin; Intravenous; Knowledge; Length of Stay; Lipids; Lipoproteins; Literature; Lung; Measures; Metabolic; Metabolic stress; Methodology; Morbidity - disease rate; Multicenter Trials; Multiple Organ Failure; Neurologic; Nonesterified Fatty Acids; Nosocomial Infections; Operative Surgical Procedures; Organ; Outcome; Outcome Measure; Patients; Pediatric Intensive Care Units; Performance; Pilot Projects; Procedures; Protocols documentation; Public Health; Publishing; Quality of life; Randomized; Randomized Clinical Trials; Recommendation; Research; Research Personnel; Respiratory Failure; Risk; Safety; Sepsis; Serum; System; Testing; Time; Titrations; Triglycerides; United States National Institutes of Health; Urinary tract; Ventilator; Weight; clinical practice; comparative effectiveness; compare effectiveness; evidence base; experience; glucose monitor; glycemic control; improved; indexing; innovation; insulin sensitivity; mortality; neurobehavioral; novel; pediatric patients; prevent; primary outcome; randomized trial; secondary outcome; treatment strategy; wound

DESCRIPTION (provided by applicant): Heart and lung failure are the most common causes of death in critically ill children in Pediatric Intensive Care Units (PICUs). Hyperglycemia is common, and the timing, intensity, duration and variability of serum glucose are associated with morbidity and mortality. Tight glycemic control (TGC) to normalize blood glucose concentrations with intravenous insulin significantly reduced mortality and morbidity in selected critically ill adult surgical patients, but recent large adult studies show statistically significant increases in mortality and hypoglycemia when TGC is deployed without adequately explicit algorithms or continuous glucose monitoring. The only single-center PICU trial of TGC showed a 55% decrease in 30-day mortality and 10% reduction in PICU length of stay (LOS), despite an extremely high rate of severe hypoglycemia. Theoretical consequences of hypoglycemia in the developing pediatric brain are greater threats than for adults. Therefore, recommendations for clinical practice cannot legitimately be made without a protocol that mitigates these risks. The critical gap in knowledge is whether safe and effective TGC can reduce morbidity and mortality in children with heart and lung failure sufficiently to justify a low risk of hypoglycemia. To evaluate the efficacy of our innovative and safe TGC protocol to reduce mortality and PICU LOS in critically ill children, we will conduct a randomized clinical trial (RCT) in 20 PICUs, called HALF-PINT: Heart and Lung Failure - Pediatric INsulin Titration trial. Patients with cardiovascular and/or respiratory failure who develop hyperglycemia will be randomized to either a Normal-TGC group in which insulin will be infused to reduce glucose concentrations into the normal target range of 80-110 mg/dL or to a High-TGC group in which glucose will be reduced into the higher 150-180 mg/dL range, a range advocated by some adult data. Both groups will receive identical standardized intravenous glucose at an age-appropriate rate in order to provide basal calories and prevent hypoglycemia. Insulin infusions will be titrated with an explicit algorithm combined with continuous glucose monitoring using a system that has been safely implemented in >500 critically ill infants and children. This study will test the primary hypothesis that patients assigned to the NL-TGC group will have a combined outcome of lower mortality and shorter PICU LOS compared with HI-TGC. The protocol will also evaluate the ability of NL-TGC to reduce the rate of accumulation of organ dysfunction, increase ventilator-free days, reduce incidence of nosocomial infections and improve neurodevelopmental outcomes at 1 year after their PICU course. This RCT will have a significant impact on public health in that its results will inform the broad practice of pediatric critical care nationally by providing evidence-based guidance regarding this critically important and controversial issue.

描述（由申请人提供）：心脏和肺部失败是小儿重症监护病房（PICUS）中重症儿童死亡的最常见原因。高血糖很常见，血清葡萄糖的时机，强度，持续时间和变异性与发病率和死亡率有关。紧密的血糖对照（TGC）使静脉内胰岛素的血糖浓度正常化，可显着降低选定的成年成人手术患者的死亡率和发病率，但是最近的大型成人研究表明，当TGC被统计上显着增加，而当TGC被统计学上显着增加而无需明确地透明的Algorice Algorice Algorithams contraclicit Algorithm contress contince contress contince contracemiation。 TGC的唯一单中心PICU试验显示，尽管严重低血糖率极高，但TGC的30天死亡率降低了55％，PICU住院时间降低了10％（LOS）。与成年人相比，发育中的小儿大脑中低血糖的理论后果是更大的威胁。因此，没有减轻这些风险的方案，就无法合法提出有关临床实践的建议。知识的关键差距是安全有效的TGC是否可以降低心脏和肺部失败儿童的发病率和死亡率，以证明低血糖的风险低。 为了评估我们创新且安全的TGC方案的疗效，以降低重症儿童的死亡率和PICU LOS，我们将在20个PICUS中进行一项随机临床试验（RCT），称为Half Pint：Heart and Lung Fail-肺部和肺衰竭 - 小儿胰岛素滴定试验。心血管和/或呼吸衰竭的患者将随机分为正常TGC组，其中胰岛素将被注入以降低葡萄糖浓度为80-110 mg/dl的正常靶标范围，或者降低了高-TGC组的葡萄糖，在该靶标范围内将葡萄糖降低到高于150-180 mg/dl范围的高等150-180 mg/dl范围。两组将以适合年龄的速率获得相同的标准静脉葡萄糖，以提供基础卡路里并预防低血糖。胰岛素输注将使用一种明确的算法与连续葡萄糖进行滴定，并使用已在> 500个重症患者和儿童中安全实施的系统进行连续的葡萄糖监测。 这项研究将测试分配给NL-TGC组的患者的主要假设，将其与HI-TGC相比，其死亡率较低和较短的PICU LOS的综合结果。该方案还将评估NL-TGC降低器官功能障碍积累的能力，增加无通风机的天数，降低医生感染的发生率并在其PICU课程后1年改善神经发育结果。该RCT将对公共卫生产生重大影响，因为其结果将通过提供有关这一至关重要且有争议的问题的基于证据的指导来为全国儿科重症监护的广泛实践提供依据。