Heart And Lung Failure - Pediatric INsulin Titration Trial (HALF-PINT)
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.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Heart And Lung Failure - Pediatric INsulin Titration Trial (HALF-PINT)|
- ICU-Free Days [ Time Frame: Study day 28 ]28-day hospital mortality-adjusted ICU length of stay
- 90-day Hospital Mortality [ Time Frame: 90 days after randomization ]In order to enable direct comparisons between data gathered in HALF-PINT and the prior adult NICE-SUGAR trial, we will collect data on 90-day hospital mortality.
- Accumulation of Multiple Organ Dysfunction Syndrome (MODS) [ Time Frame: 28 days after randomization ]Accumulation of MODS during the 28 days following randomization will be measured. MODS is defined as the concurrent dysfunction of two or more organ systems (e.g., acute lung injury and renal failure). The clinical relevance of MODS as a surrogate outcome measure is well recognized in the intensive care community, and there is a clear relationship between the number of dysfunctional organ systems and the risk of death in critically ill children.
- Ventilator-Free Days [ Time Frame: 28 days following randomization ]Ventilator-free days during the 28 days following randomization encompasses both reduction in the duration of ventilation and improvement in mortality. The end of the subject's duration of ventilation is defined as the date/time of extubation for subjects who are intubated, or the date/time of the discontinuation of mechanical ventilation for subjects with tracheostomy.
- Incidence of Nosocomial Infections [ Time Frame: Up to 48 hours after ICU discharge ]We will use Centers for Disease Control's (CDC) most recently published definitions for the following nosocomial infections attributable to the ICU stay: total bloodstream infections including Central Venous Line (CVL)-associated bloodstream infections (BSI), respiratory tract infections including ventilator-associated pneumonias, urinary tract infections, and wound infections that occur in the ICU or within 48 hours of discharge to the non-ICU inpatient unit. Device-related infections will be counted per 1,000 device days, and non-device-related infections will be counted per 1,000 ICU days.
- Insulin Algorithm Safety [ Time Frame: Participants will be followed for the duration of ICU stay, an expected average of 8 days ]Hypoglycemia will be tracked and reported according to three ranges: severe (SH; <40 mg/dL), moderate (40-49 mg/dL), and mild (50-59 mg/dL) per subject and per subject per insulin day. Lipid activation and metabolic stress during SH will be measured by urgently drawing and sending blood to the local central laboratory for determination of serum glucose, serum triglycerides, free fatty acids, lipoprotein profile, and lactate. As insulin infusion can cause slight changes to serum potassium concentration, hypokalemia <2.5 mmol/L will also be tracked.
- Developmental Neurobehavioral Outcomes [ Time Frame: Baseline and 1 year after ICU course ]Reliable, reproducible measures of adaptive functioning, behavior, and quality of life will be used to determine outcomes at baseline (CBCL, PedsQL) and at one year after ICU discharge (Vineland-II, CBCL, PedsQL). The goal of baseline data collection is to assess pre-ICU health and quality of life.
- Nursing Workload [ Time Frame: Multiple intervals during the study period ]The cognitive burden placed upon bedside nurses when managing a patient on TGC will be described. Bedside nurses will be randomly selected to complete an anonymous survey describing their perceptions of workload burden associated with managing a patient on TGC. Nurses' perceptions of their capacity to complete both TGC‐related and non TGC-related nursing activities over several intervals of the study period will be described via qualitative and summary statistics.
- Insulin Algorithm Performance [ Time Frame: Until study discharge, up to 28 days following randomization ]Performance of the algorithm across diverse ages, weights, and disease processes will be critical to measure and compare to other published algorithm performance. Ideally, the algorithm will minimize time to glucose target range and maximize time spent in the glucose target range. We will track the overall glycemic profile using time-weighted glucose average because it is uniquely unaffected by the increased frequency of BG determinations that occur when glucose is abnormally low or high. Based upon insulin requirements, we will calculate insulin sensitivity index (ISI) in the first 24 hours of the protocol, as well as glucose variability index in the first 72 hours.
|Study Start Date:||March 2012|
|Estimated Study Completion Date:||November 2017|
|Primary Completion Date:||September 2016 (Final data collection date for primary outcome measure)|
Active Comparator: 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.
IV insulin titration to target a blood glucose of 80-110 mg/dL
Active Comparator: 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.
IV insulin titration to target a blood glucose of 150-180 mg/dL
Please refer to this study by its ClinicalTrials.gov identifier: NCT01565941
Show 35 Study Locations
|Principal Investigator:||Michael SD Agus, MD||Boston Children’s Hospital|
|Principal Investigator:||Vinay M Nadkarni, MD||Children's Hospital of Philadelphia|