Trial Outcomes & Findings for Heart And Lung Failure - Pediatric INsulin Titration Trial (NCT NCT01565941)

NCT ID: NCT01565941

Last Updated: 2022-07-25

Results Overview

28-day hospital mortality-adjusted ICU length of stay.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 713 participants
• Primary outcome timeframe: Study day 28
• Results posted on: 2022-07-25

Participant Flow

Participant milestones

Measure	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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
Overall Study STARTED	360	353
Overall Study COMPLETED	349	349
Overall Study NOT COMPLETED	11	4

Reasons for withdrawal

Measure	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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
Overall Study Withdrawn by parent/guardian	3	2
Overall Study Randomized; did not receive intevention	8	2

Baseline Characteristics

Heart And Lung Failure - Pediatric INsulin Titration Trial

Baseline characteristics by cohort

Measure	Tight Glycemic Control 1 (TGC-1) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL	Total n=698 Participants Total of all reporting groups
Age, Categorical <=18 years	349 Participants n=5 Participants	349 Participants n=7 Participants	698 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	5.5 Years n=5 Participants	6.7 Years n=7 Participants	6.2 Years n=5 Participants
Sex: Female, Male Female	164 Participants n=5 Participants	169 Participants n=7 Participants	333 Participants n=5 Participants
Sex: Female, Male Male	185 Participants n=5 Participants	180 Participants n=7 Participants	365 Participants n=5 Participants
Region of Enrollment Canada	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment United States	348 participants n=5 Participants	348 participants n=7 Participants	696 participants n=5 Participants

PRIMARY outcome

Timeframe: Study day 28

28-day hospital mortality-adjusted ICU length of stay.

Outcome measures

Measure	Tight Glycemic Control 1 (TGC-1) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
ICU-Free Days	20 Days Interval 1.0 to 24.2	19.4 Days Interval 7.1 to 23.9

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Tight Glycemic Control 1 (TGC-1) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
90-day Hospital Mortality	52 Participants	40 Participants

SECONDARY outcome

Timeframe: 28 days after randomization

We will collect data on 28-day hospital mortality.

Outcome measures

Measure	Tight Glycemic Control 1 (TGC-1) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
28-day Hospital Mortality	47 Participants	32 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Tight Glycemic Control 1 (TGC-1) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
Accumulation of Multiple Organ Dysfunction Syndrome (MODS)	326 Participants	324 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Tight Glycemic Control 1 (TGC-1) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
Ventilator-Free Days	21.8 Days Interval 8.4 to 25.0	20.9 Days Interval 11.9 to 24.4

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Tight Glycemic Control 1 (TGC-1) n=97 Participants 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=111 Participants 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
Developmental Neurobehavioral Outcomes: VABS-II Composite	79.9 Score on a scale Standard Deviation 25.5	79.4 Score on a scale Standard Deviation 26.9

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Tight Glycemic Control 1 (TGC-1) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
Participants With Device-Related or Non-Device Related Nosocomial Infection	12 Participants	4 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Tight Glycemic Control 1 (TGC-1) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
Incidence of Catheter-Associated Bloodstream Infection	1.94 Infections/1000 CVC days	0 Infections/1000 CVC days

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Tight Glycemic Control 1 (TGC-1) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
Incidence of Catheter-Associated Urinary Tract Infection	2.19 Infections/1000 bladder catheter days	1.79 Infections/1000 bladder catheter days

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Tight Glycemic Control 1 (TGC-1) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
Incidence of Ventilator-Associated Pneumonia	0.94 Infections/1000 ventilator days	0 Infections/1000 ventilator days

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Tight Glycemic Control 1 (TGC-1) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
Incidence of Wound Infection Incidence of Wound Infection	0 Infections/1000 ICU days	0 Infections/1000 ICU days

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Tight Glycemic Control 1 (TGC-1) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
Participants With Severe Hypoglycemia (<40 mg/dL), Unrelated to Insulin Infusion (Insulin Algorithm Safety)	5 Participants	6 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Tight Glycemic Control 1 (TGC-1) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
Participants With Severe Hypoglycemia (<40 mg/dL), Related to Insulin Infusion (Insulin Algorithm Safety)	13 Participants	1 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Tight Glycemic Control 1 (TGC-1) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
Participants With Any Hypoglycemia (<60 mg/dL), Unrelated to Insulin Infusion (Insulin Algorithm Safety)	26 Participants	29 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Tight Glycemic Control 1 (TGC-1) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
Participants With Any Hypoglycemia (<60 mg/dL), Related to Insulin Infusion (Insulin Algorithm Safety)	64 Participants	5 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Tight Glycemic Control 1 (TGC-1) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
Participants With Hypokalemia (<2.5 mmol/L)	76 Participants	64 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Tight Glycemic Control 1 (TGC-1) n=250 Participants 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=255 Participants 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
Nursing Workload: SWAT (Subjective Workload Assessment Technique) Instrument	50.0 score on a scale Interval 24.36 to 60.5	36.2 score on a scale Interval 10.5 to 50.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Tight Glycemic Control 1 (TGC-1) n=250 Participants 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=255 Participants 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
Nursing Workload: NASA-TLX (National Aeronautics and Space Administration - Task Load Index) Instrument	35.0 score on a scale Interval 15.3 to 50.0	20.4 score on a scale Interval 7.3 to 38.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Tight Glycemic Control 1 (TGC-1) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
Insulin Algorithm Performance: Time to the Target Range	5.5 Hours Interval 2.5 to 11.5	1.5 Hours Interval 0.5 to 3.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Tight Glycemic Control 1 (TGC-1) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
Insulin Algorithm Performance: Time in the Target Range	57 Percentage of time Interval 43.0 to 67.0	91 Percentage of time Interval 81.0 to 96.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Tight Glycemic Control 1 (TGC-1) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=349 Participants 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
Insulin Algorithm Performance: Time-Weighted Glucose Average	109 mg/dL Interval 102.0 to 118.0	123 mg/dL Interval 108.0 to 142.0

Adverse Events

Tight Glycemic Control 1 (TGC-1)

Serious events: 18 serious events

Other events: 122 other events

Deaths: 0 deaths

Tight Glycemic Control 2 (TGC-2)

Serious events: 7 serious events

Other events: 112 other events

Deaths: 0 deaths

Serious adverse events

Measure	Tight Glycemic Control 1 (TGC-1) n=349 participants at risk 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=349 participants at risk 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
Endocrine disorders Severe hypoglycemia (BG < 40 mg/dL) Unrelated to insulin administration	1.4% 5/349 • Entire course of protocol, up to 28 days	1.7% 6/349 • Entire course of protocol, up to 28 days
Endocrine disorders Severe hypoglycemia (BG < 40 mg/dL) Related to insulin administration	3.7% 13/349 • Entire course of protocol, up to 28 days	0.29% 1/349 • Entire course of protocol, up to 28 days

Other adverse events

Measure	Tight Glycemic Control 1 (TGC-1) n=349 participants at risk 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. Insulin: IV insulin titration to target a blood glucose of 80-110 mg/dL	Tight Glycemic Control 2 (TGC-2) n=349 participants at risk 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. Insulin: IV insulin titration to target a blood glucose of 150-180 mg/dL
Endocrine disorders Hypokalemia (< 2.5 mmol/L)	21.8% 76/349 • Entire course of protocol, up to 28 days	18.3% 64/349 • Entire course of protocol, up to 28 days
Nervous system disorders New seizure	1.4% 5/349 • Entire course of protocol, up to 28 days	2.9% 10/349 • Entire course of protocol, up to 28 days
Infections and infestations Health-care associated infection	3.4% 12/349 • Entire course of protocol, up to 28 days	1.1% 4/349 • Entire course of protocol, up to 28 days
Infections and infestations Infection with positive culture	8.3% 29/349 • Entire course of protocol, up to 28 days	9.7% 34/349 • Entire course of protocol, up to 28 days

Additional Information

Dr. Michael Agus

Boston Children's Hospital

Phone: 617-355-5849

Email: michael.agus@childrens.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place