Heart And Lung Failure - Pediatric INsulin Titration Trial (HALF-PINT)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 713
- 试验地点
- 35
- 主要终点
- ICU-Free Days
研究概览
简要总结
Stress hyperglycemia, a state of abnormal metabolism with supra-normal blood glucose levels, is often seen in critically ill patients. Tight glycemic control (TGC) was originally shown to reduce morbidity and mortality in a landmark randomized clinical trial (RCT) of adult critically ill surgical patients but has since come under intense scrutiny due to conflicting results in recent adult trials. One pediatric RCT has been published to date that demonstrated survival benefit but was complicated by an unacceptably high rate of severe hypoglycemia. The Heart And Lung Failure - Pediatric INsulin Titration (HALF-PINT) trial is a multi-center, randomized clinical treatment trial comparing two ranges of glucose control in hyperglycemic critically ill children with heart and/or lung failure. Both target ranges of glucose control fall within the range of "usual care" for critically ill children managed in pediatric intensive care units.
The purpose of the study is to determine the comparative effectiveness of tight glycemic control to a target range of 80-110 mg/dL (TGC-1, 4.4-6.1 mmol/L) vs. a target range of 150-180 mg/dL (TGC-2, 8.3-10.0 mmol/L) on hospital mortality and intensive care unit (ICU) length of stay (LOS) in hyperglycemic critically ill children with cardiovascular and/or respiratory failure. This will be accomplished using an explicit insulin titration algorithm and continuous glucose monitoring to safely achieve these glucose targets. Both groups will receive identical standardized intravenous glucose at an age-appropriate rate in order to provide basal calories and mitigate hypoglycemia. Insulin infusions will be titrated with an explicit algorithm combined with continuous glucose monitoring using a protocol that has been safely implemented in 490 critically ill infants and children.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Weeks 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cardiovascular failure and/or respiratory failure:
- •Cardiovascular Failure: Dopamine or dobutamine > 5 mcg/kg/min, or any dose of epinephrine, norepinephrine, phenylephrine, milrinone or vasopressin if used to treat hypotension.
- •Respiratory Failure: Acute mechanical ventilation via endotracheal tube or tracheostomy.
- •Age >= 2 weeks and corrected gestational age >= 42 weeks
- •Age < 18 years (has not yet had 18th birthday)
排除标准
- •No longer has cardiovascular or respiratory failure (as defined in inclusion criterion 1), or is expected to be extubated in the next 24 hours
- •Expected to remain in ICU < 24 hours
- •Previously randomized in HALF-PINT
- •Enrolled in a competing clinical trial
- •Family/team decision to limit/redirect from aggressive ICU technological support
- •Chronic ventilator dependence prior to ICU admission (non-invasive ventilation and ventilation via tracheostomy overnight or during sleep are acceptable)
- •Type 1 or 2 diabetes
- •Cardiac surgery within prior 2 months or during/planned for this hospitalization (extra-corporeal life support or non-cardiac surgery is acceptable)
- •Diffuse skin disease that does not allow securement of a subcutaneous sensor
- •Therapeutic plan to remain intubated for >28 days
- •Receiving therapeutic cooling with targeted body temperatures <34 degrees Celsius
- •Current or planned ketogenic diet
- •Ward of the state
- •Pregnancy
研究组 & 干预措施
Tight Glycemic Control 1 (TGC-1)
Approximately half of the subjects randomized into HALF-PINT will be randomized into TGC-1 which will seek to maintain the subject's blood sugar between 80-110 mg/dL. Intravenous insulin may be administered per insulin algorithm.
干预措施: Insulin (Drug)
Tight Glycemic Control 2 (TGC-2)
Approximately half of the subjects randomized into HALF-PINT will be randomized into TGC-2 which will seek to maintain the subject's blood sugar between 150-180 mg/dL. Intravenous insulin may be administered per insulin algorithm.
干预措施: Insulin (Drug)
结局指标
主要结局
ICU-Free Days
时间窗: Study day 28
28-day hospital mortality-adjusted ICU length of stay.
次要结局
- 28-day Hospital Mortality(28 days after randomization)
- Ventilator-Free Days(28 days following randomization)
- Nursing Workload: NASA-TLX (National Aeronautics and Space Administration - Task Load Index) Instrument(One nursing shift caring for patient on TGC, at anytime during the patient's hospital stay through the tenth nursing shift for the patient. Shift determined randomly by the last digit of the study ID number, 0-9 (0=shift 10, 1=shift 1, 2=shift 2, etc.).)
- Insulin Algorithm Performance: Time in the Target Range(Until study discharge, up to 28 days following randomization)
- 90-day Hospital Mortality(90 days after randomization)
- Accumulation of Multiple Organ Dysfunction Syndrome (MODS)(28 days after randomization)
- Participants With Severe Hypoglycemia (<40 mg/dL), Related to Insulin Infusion (Insulin Algorithm Safety)(Participants will be followed for the duration of ICU stay, an expected average of 8 days)
- Participants With Any Hypoglycemia (<60 mg/dL), Unrelated to Insulin Infusion (Insulin Algorithm Safety)(Participants will be followed for the duration of ICU stay, an expected average of 8 days)
- Participants With Any Hypoglycemia (<60 mg/dL), Related to Insulin Infusion (Insulin Algorithm Safety)(Participants will be followed for the duration of ICU stay, an expected average of 8 days)
- Developmental Neurobehavioral Outcomes: VABS-II Composite(One year after ICU course)
- Participants With Device-Related or Non-Device Related Nosocomial Infection(Up to 48 hours after ICU discharge)
- Incidence of Catheter-Associated Urinary Tract Infection(Up to 48 hours after ICU discharge)
- Participants With Severe Hypoglycemia (<40 mg/dL), Unrelated to Insulin Infusion (Insulin Algorithm Safety)(Participants will be followed for the duration of ICU stay, an expected average of 8 days)
- Insulin Algorithm Performance: Time to the Target Range(Until study discharge, up to 28 days following randomization)
- Incidence of Catheter-Associated Bloodstream Infection(Up to 48 hours after ICU discharge)
- Incidence of Ventilator-Associated Pneumonia(Up to 48 hours after ICU discharge)
- Incidence of Wound Infection Incidence of Wound Infection(Up to 48 hours after ICU discharge)
- Participants With Hypokalemia (<2.5 mmol/L)(Participants will be followed for the duration of ICU stay, an expected average of 8 days)
- Nursing Workload: SWAT (Subjective Workload Assessment Technique) Instrument(One nursing shift caring for patient on TGC, at anytime during the patient's hospital stay through the tenth nursing shift for the patient. Shift determined randomly by the last digit of the study ID number, 0-9 (0=shift 10, 1=shift 1, 2=shift 2, etc.).)
- Insulin Algorithm Performance: Time-Weighted Glucose Average(Until study discharge, up to 28 days following randomization)
研究者
Michael Agus
Associate Professor of Pediatrics, Harvard Medical School
Boston Children's Hospital