Heart And Lung Failure - Pediatric INsulin Titration Trial
- Registration Number
- NCT01565941
- Lead Sponsor
- Boston Children's Hospital
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 713
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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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tight Glycemic Control 2 (TGC-2) Insulin 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. Tight Glycemic Control 1 (TGC-1) Insulin 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.
- Primary Outcome Measures
Name Time Method ICU-Free Days Study day 28 28-day hospital mortality-adjusted ICU length of stay.
- Secondary Outcome Measures
Name Time Method 28-day Hospital Mortality 28 days after randomization We will collect data on 28-day hospital mortality.
Ventilator-Free Days 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.
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.). 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.
Using the NASA-TLX instrument, perceived workload of Pediatric Intensive Care Nurses caring for HALF-PINT patients in TGC group 1 and TGC group 2 were assessed. The instrument uses a ranking system to weight perceived workload which results in an overall sore ranging from 0-100, where higher scores indicate higher perceived workload. It obtains overall perception of workload related to stressful tasks and includes 6 dimensions (cognitive demand, physical demand, time pressure, performance, effort, and frustration.Insulin Algorithm Performance: Time in the Target Range 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 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.
90-day Hospital Mortality 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) 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.
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 Hypoglycemia will be tracked and reported according to three ranges: severe (\<40 mg/dL), moderate (40-49 mg/dL) and mild (50-59 mg/dL). As insulin infusion can cause slight changes to serum potassium concentration, hypokalemia \<2.5 mmol/L will also be tracked.
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 Hypoglycemia will be tracked and reported according to three ranges: severe (\<40 mg/dL), moderate (40-49 mg/dL) and mild (50-59 mg/dL). As insulin infusion can cause slight changes to serum potassium concentration, hypokalemia \<2.5 mmol/L will also be tracked.
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 Hypoglycemia will be tracked and reported according to three ranges: severe (\<40 mg/dL), moderate (40-49 mg/dL) and mild (50-59 mg/dL). As insulin infusion can cause slight changes to serum potassium concentration, hypokalemia \<2.5 mmol/L will also be tracked.
Developmental Neurobehavioral Outcomes: VABS-II Composite One 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. The results of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) are reported. Scores range from 20-160, with higher scores being better.
Participants With Device-Related or Non-Device Related Nosocomial Infection 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.
Incidence of Catheter-Associated Urinary Tract Infection Up to 48 hours after ICU discharge We will use Centers for Disease Control's (CDC) most recently published definition for the following nosocomial infection attributable to the ICU stay: urinary tract infections that occur in the ICU or within 48 hours of discharge to the non-ICU inpatient unit. This device-related infection will be counted per 1,000 device days.
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 Hypoglycemia will be tracked and reported according to three ranges: severe (\<40 mg/dL), moderate (40-49 mg/dL) and mild (50-59 mg/dL). As insulin infusion can cause slight changes to serum potassium concentration, hypokalemia \<2.5 mmol/L will also be tracked.
Insulin Algorithm Performance: Time to the Target Range 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. 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.
Incidence of Catheter-Associated Bloodstream Infection Up to 48 hours after ICU discharge We will use Centers for Disease Control's (CDC) most recently published definition for the following nosocomial infection attributable to the ICU stay: Central Venous Line (CVL)-associated bloodstream infections (BSI) that occur in the ICU or within 48 hours of discharge to the non-ICU inpatient unit. This device-related infection will be counted per 1,000 device days.
Incidence of Ventilator-Associated Pneumonia Up to 48 hours after ICU discharge We will use Centers for Disease Control's (CDC) most recently published definition for the following nosocomial infection attributable to the ICU stay: respiratory tract infections including ventilator-associated pneumonias that occur in the ICU or within 48 hours of discharge to the non-ICU inpatient unit. This device-related infection will be counted per 1,000 device days.
Incidence of Wound Infection Incidence of Wound Infection Up to 48 hours after ICU discharge We will use Centers for Disease Control's (CDC) most recently published definition for the following nosocomial infection attributable to the ICU stay: wound infections that occur in the ICU or within 48 hours of discharge to the non-ICU inpatient unit. This non-device-related infection will be counted per 1,000 ICU days.
Participants With Hypokalemia (<2.5 mmol/L) 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 (\<40 mg/dL), moderate (40-49 mg/dL) and mild (50-59 mg/dL). As insulin infusion can cause slight changes to serum potassium concentration, hypokalemia \<2.5 mmol/L will also be tracked.
Insulin Algorithm Performance: Time-Weighted Glucose Average 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. 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.
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.). The workload 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 during one shift.
Using the SWAT (Subjective Workload Assessment Technique) instrument, perceived workload of Pediatric Intensive Care Nurses caring for HALF-PINT patients in TGC group 1 and TGC group 2 were assessed. The SWAT has been used to study the effect of workload in the fields of nursing, pharmacy and medicine. It measures the following burdens: cognitive (mental effort or concentration required for complexity of task), time (amount of spare time, interruptions, overlapping tasks) and psychological stress associated with work that impacts performance. The SWAT uses a ranking system to weight perceived workload which results in an overall score ranging from 0-100, where higher scores indicate higher perceived workload.
Trial Locations
- Locations (35)
Morgan Stanley Children's Hospital of New York
🇺🇸New York, New York, United States
Nemours/A.I DuPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
The Children's Hospital at Montefiore
🇺🇸Bronx, New York, United States
Westchester Medical Center
🇺🇸Valhalla, New York, United States
Medical City Children's Dallas
🇺🇸Dallas, Texas, United States
CHU Sainte-Justine
🇨🇦Montreal, Quebec, Canada
Women and Children's Hospital of Buffalo
🇺🇸Buffalo, New York, United States
Children's Medical Center Dallas
🇺🇸Dallas, Texas, United States
The Royal Children's Hospital
🇦🇺Melbourne, Victoria, Australia
Miller Children's Hospital Long Beach
🇺🇸Long Beach, California, United States
Children's Hospital & Research Center of Oakland
🇺🇸Oakland, California, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
St. Louis Children's Hospital
🇺🇸Saint Louis, Missouri, United States
North Shore LIJ Cohen Children's Medical Center
🇺🇸New Hyde Park, New York, United States
Children's Hospital of Los Angelos
🇺🇸Los Angeles, California, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
Mattel Children's Hospital
🇺🇸Los Angeles, California, United States
Ann & Robert H. Lurie Children's Hospital pf Chicago
🇺🇸Chicago, Illinois, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Cincinnati Children's Hospital
🇺🇸Cincinnati, Ohio, United States
UCSF Benioff Children's Hospital
🇺🇸San Francisco, California, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Yale-New Haven Children's Hospital
🇺🇸New Haven, Connecticut, United States
University of Chicago Comer Children's Hospital
🇺🇸Chicago, Illinois, United States
C.S. Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
Duke Children's Hospital and Medical Center
🇺🇸Durham, North Carolina, United States
The Children's Hospital at OU Medical Center
🇺🇸Oklahoma City, Oklahoma, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Healthcare of Atlanta
🇺🇸Atlanta, Georgia, United States
Penn State Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States