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.
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.
Brief Title
Heart And Lung Failure - Pediatric INsulin Titration Trial
Categories
Completion Date
Completion Date Type
Actual
Conditions
Heart Failure
Respiratory Failure
Eligibility Criteria
Inclusion Criteria:
* Cardiovascular failure and/or respiratory failure:
1. Cardiovascular Failure: Dopamine or dobutamine \> 5 mcg/kg/min, or any dose of epinephrine, norepinephrine, phenylephrine, milrinone or vasopressin if used to treat hypotension.
2. 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)
Exclusion Criteria:
* 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
* Cardiovascular failure and/or respiratory failure:
1. Cardiovascular Failure: Dopamine or dobutamine \> 5 mcg/kg/min, or any dose of epinephrine, norepinephrine, phenylephrine, milrinone or vasopressin if used to treat hypotension.
2. 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)
Exclusion Criteria:
* 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
Inclusion Criteria
Inclusion Criteria:
* Cardiovascular failure and/or respiratory failure:
1. Cardiovascular Failure: Dopamine or dobutamine \> 5 mcg/kg/min, or any dose of epinephrine, norepinephrine, phenylephrine, milrinone or vasopressin if used to treat hypotension.
2. 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)
* Cardiovascular failure and/or respiratory failure:
1. Cardiovascular Failure: Dopamine or dobutamine \> 5 mcg/kg/min, or any dose of epinephrine, norepinephrine, phenylephrine, milrinone or vasopressin if used to treat hypotension.
2. 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)
Gender
All
Gender Based
false
Keywords
Cardiovascular
Respiratory
Failure
Heart
Lung
Continuous glucose monitoring
Tight glycemic control
Subcutaneous
Insulin
Algorithm
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
17 Years
Minimum Age
2 Weeks
NCT Id
NCT01565941
Org Class
Other
Org Full Name
Boston Children's Hospital
Org Study Id
IRB-P00002310
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Heart And Lung Failure - Pediatric INsulin Titration Trial (HALF-PINT)
Primary Outcomes
Outcome Description
28-day hospital mortality-adjusted ICU length of stay.
Outcome Measure
ICU-Free Days
Outcome Time Frame
Study day 28
Secondary Ids
Secondary Id
U01HL107681
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
90 days after randomization
Outcome Measure
90-day Hospital Mortality
Outcome Description
We will collect data on 28-day hospital mortality.
Outcome Time Frame
28 days after randomization
Outcome Measure
28-day Hospital Mortality
Outcome Description
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.
Outcome Time Frame
28 days after randomization
Outcome Measure
Accumulation of Multiple Organ Dysfunction Syndrome (MODS)
Outcome Description
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.
Outcome Time Frame
28 days following randomization
Outcome Measure
Ventilator-Free Days
Outcome Description
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.
Outcome Time Frame
One year after ICU course
Outcome Measure
Developmental Neurobehavioral Outcomes: VABS-II Composite
Outcome Description
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.
Outcome Time Frame
Up to 48 hours after ICU discharge
Outcome Measure
Participants With Device-Related or Non-Device Related Nosocomial Infection
Outcome Description
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.
Outcome Time Frame
Up to 48 hours after ICU discharge
Outcome Measure
Incidence of Catheter-Associated Bloodstream Infection
Outcome Description
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.
Outcome Time Frame
Up to 48 hours after ICU discharge
Outcome Measure
Incidence of Catheter-Associated Urinary Tract Infection
Outcome Description
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.
Outcome Time Frame
Up to 48 hours after ICU discharge
Outcome Measure
Incidence of Ventilator-Associated Pneumonia
Outcome Description
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.
Outcome Time Frame
Up to 48 hours after ICU discharge
Outcome Measure
Incidence of Wound Infection Incidence of Wound Infection
Outcome Description
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.
Outcome Time Frame
Participants will be followed for the duration of ICU stay, an expected average of 8 days
Outcome Measure
Participants With Severe Hypoglycemia (<40 mg/dL), Unrelated to Insulin Infusion (Insulin Algorithm Safety)
Outcome Description
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.
Outcome Time Frame
Participants will be followed for the duration of ICU stay, an expected average of 8 days
Outcome Measure
Participants With Severe Hypoglycemia (<40 mg/dL), Related to Insulin Infusion (Insulin Algorithm Safety)
Outcome Description
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.
Outcome Time Frame
Participants will be followed for the duration of ICU stay, an expected average of 8 days
Outcome Measure
Participants With Any Hypoglycemia (<60 mg/dL), Unrelated to Insulin Infusion (Insulin Algorithm Safety)
Outcome Description
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.
Outcome Time Frame
Participants will be followed for the duration of ICU stay, an expected average of 8 days
Outcome Measure
Participants With Any Hypoglycemia (<60 mg/dL), Related to Insulin Infusion (Insulin Algorithm Safety)
Outcome Description
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.
Outcome Time Frame
Participants will be followed for the duration of ICU stay, an expected average of 8 days
Outcome Measure
Participants With Hypokalemia (<2.5 mmol/L)
Outcome Description
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.
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.
Outcome Time Frame
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.).
Outcome Measure
Nursing Workload: SWAT (Subjective Workload Assessment Technique) Instrument
Outcome Description
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.
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.
Outcome Time Frame
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.).
Outcome Measure
Nursing Workload: NASA-TLX (National Aeronautics and Space Administration - Task Load Index) Instrument
Outcome Description
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.
Outcome Time Frame
Until study discharge, up to 28 days following randomization
Outcome Measure
Insulin Algorithm Performance: Time to the Target Range
Outcome Description
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.
Outcome Time Frame
Until study discharge, up to 28 days following randomization
Outcome Measure
Insulin Algorithm Performance: Time in the Target Range
Outcome Description
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.
Outcome Time Frame
Until study discharge, up to 28 days following randomization
Outcome Measure
Insulin Algorithm Performance: Time-Weighted Glucose Average
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Maximum Age Number (converted to Years and rounded down)
17
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
Shivanand Medar
Investigator Email
smedar@montefiore.org
Investigator Phone
718-741-2491
Categories Mesh Debug
Heart/Cardiovascular --- HEART FAILURE
Diabetes & Endocrine System --- INSULIN RESISTANCE
Brain, Spinal Cord & Nervous System --- HEART DISEASES
Heart/Cardiovascular --- HEART DISEASES
Blood Disorders --- CARDIOVASCULAR DISEASES
Blood & Bone Marrow Cancers --- CARDIOVASCULAR DISEASES
Heart/Cardiovascular --- CARDIOVASCULAR DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
Diabetes --- GLUCOSE METABOLISM DISORDERS
Diabetes & Endocrine System --- GLUCOSE METABOLISM DISORDERS
Diabetes --- METABOLIC DISEASES
Diabetes & Endocrine System --- METABOLIC DISEASES
MeSH Terms
HEART FAILURE
RESPIRATORY INSUFFICIENCY
INSULIN RESISTANCE
HEART DISEASES
CARDIOVASCULAR DISEASES
RESPIRATION DISORDERS
RESPIRATORY TRACT DISEASES
HYPERINSULINISM
GLUCOSE METABOLISM DISORDERS
METABOLIC DISEASES
NUTRITIONAL AND METABOLIC DISEASES
INSULIN
PROINSULIN
INSULINS
PANCREATIC HORMONES
PEPTIDE HORMONES
HORMONES
HORMONES, HORMONE SUBSTITUTES, AND HORMONE ANTAGONISTS
PEPTIDES
AMINO ACIDS, PEPTIDES, AND PROTEINS