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 >900 critically ill infants and children.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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 ] [ Designated as safety issue: No ]28-day hospital mortality-adjusted ICU length of stay
- 90-day Hospital Mortality [ Time Frame: 90 days after randomization ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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. ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: No ]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 hospitalization (Vineland-II, CBCL, PedsQL). The goal of baseline data collection is to assess pre-ICU health and quality of life.
|Study Start Date:||March 2012|
|Estimated Study Completion Date:||January 2017|
|Estimated Primary Completion Date:||January 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.
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.
IV insulin titration to target a blood glucose of 150-180 mg/dL
|Contact: Michael SD Agus, MD||617 355-6000|
|Contact: Vinay M Nadkarni, MD||215 590-1000|
|United States, California|
|Children's Hospital of Los Angelos||Not yet recruiting|
|Los Angeles, California, United States, 90027|
|Contact: Christopher Newth, MD 323-660-2450|
|Principal Investigator: Christopher Newth, MD|
|United States, Colorado|
|Children's Hospital Colorado||Recruiting|
|Aurora, Colorado, United States, 80045|
|Contact: Peter M Mourani, MD 720-777-1234|
|Principal Investigator: Peter Mourani, MD|
|Sub-Investigator: Jon Kaufman, MD|
|United States, Massachusetts|
|Children's Hospital Boston||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Michael SD Agus, MD 617-355-6000|
|Principal Investigator: Michael Agus, MD|
|United States, New York|
|Women and Children's Hospital of Buffalo||Not yet recruiting|
|Buffalo, New York, United States, 14222|
|Contact: Amanda Hassinger, MD 716-878-1859 firstname.lastname@example.org|
|Principal Investigator: Amanda Hassinger, MD|
|Morgan Stanley Children's Hospital of New York||Not yet recruiting|
|New York, New York, United States, 10032|
|Contact: Katherine Biagas, MD 212-305-8458 email@example.com|
|Principal Investigator: Katherine Biagas, MD|
|Westchester Medical Center||Recruiting|
|Valhalla, New York, United States, 10595|
|Contact: Simon Li, MD 914-493-7000|
|Principal Investigator: Simon Li, MD|
|Principal Investigator: Alan Pinto, MD|
|United States, Ohio|
|Cincinnati Children's Hospital||Recruiting|
|Cincinnati, Ohio, United States, 45229|
|Contact: Ranjit S Chima, MD 513-636-4200|
|Principal Investigator: Ranjit Chima, MD|
|United States, Pennsylvania|
|Penn State Hershey Medical Center||Recruiting|
|Hershey, Pennsylvania, United States, 17033|
|Contact: Neal J Thomas, MD 717-531-8080|
|Principal Investigator: Neal Thomas, MD|
|Sub-Investigator: Robert Tamburro, MD|
|Children's Hospital of Philadelphia||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Vijay Srinivasan, MD 215-590-1000|
|Principal Investigator: Vijay Srinivasan, MD|
|Sub-Investigator: Lauren Marsillio, MD|
|Principal Investigator:||Michael SD Agus, MD||Children's Hospital Boston|
|Principal Investigator:||Vinay M Nadkarni, MD||Children's Hospital of Philadelphia|