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

基本信息

批准号：
8712539
负责人：
MICHAEL SD AGUS
金额：
$ 56.53万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
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/8712539
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

项目摘要

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）：心力衰竭和肺衰竭是儿科重症监护病房 (PICU) 危重儿童最常见的死亡原因。高血糖很常见，血糖升高的时间、强度、持续时间和变异性与发病率和死亡率相关。通过静脉注射胰岛素使血糖浓度正常化的严格血糖控制 (TGC) 显着降低了选定的危重成人手术患者的死亡率和发病率，但最近的大型成人研究表明，当在没有足够明确的算法或连续的情况下部署 TGC 时，死亡率和低血糖率在统计学上显着增加血糖监测。 TGC 唯一的单中心 PICU 试验显示，尽管严重低血糖发生率极高，但 30 天死亡率降低了 55%，PICU 住院时间 (LOS) 缩短了 10%。理论上，低血糖对发育中的儿童大脑的影响比对成人的威胁更大。因此，如果没有减轻这些风险的方案，就无法合理地提出临床实践建议。知识上的关键差距是安全有效的 TGC 是否可以充分降低心肺衰竭儿童的发病率和死亡率，从而证明低血糖风险较低。为了评估我们创新且安全的 TGC 方案在降低危重儿童死亡率和 PICU LOS 方面的功效，我们将在 20 个 PICU 中进行一项随机临床试验 (RCT)，称为 HALF-PINT：心肺衰竭 - 儿科胰岛素滴定试验。出现高血糖的心血管和/或呼吸衰竭患者将被随机分入正常 TGC 组（其中将注射胰岛素以将血糖浓度降低至 80-110 mg/dL 的正常目标范围）或高 TGC 组其中葡萄糖将降低至较高的 150-180 mg/dL 范围，这是一些成人数据所提倡的范围。两组都将以适合年龄的速率接受相同的标准化静脉注射葡萄糖，以提供基础热量并预防低血糖。胰岛素输注将通过明确的算法与连续血糖监测相结合，使用已在超过 500 名危重婴儿和儿童中安全实施的系统进行滴定。本研究将检验主要假设，即与 HI-TGC 组相比，分配到 NL-TGC 组的患者将获得更低的死亡率和更短的 PICU LOS 的综合结果。该方案还将评估 NL-TGC 在 PICU 疗程后 1 年内降低器官功能障碍累积率、增加无呼吸机天数、降低院内感染发生率和改善神经发育结果的能力。这项随机对照试验将对公共卫生产生重大影响，因为其结果将为全国儿科重症监护的广泛实践提供信息，就这一极其重要且有争议的问题提供循证指导。