Heart And Lung Failure - Pediatric INsulin Titration Trial

Heart Failure Clinical Trial

— HALF-PINT  

Official title:

Heart And Lung Failure - Pediatric INsulin Titration Trial (HALF-PINT)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01565941
• Other study ID #: IRB-P00002310
• Secondary ID: U01HL107681
• Status: Completed
• Phase: Phase 3
• Start date: April 2012
• Est. completion date: February 2018

Study information

• Verified date: July 2022
• Source: Boston Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 713
• Est. completion date: February 2018
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Weeks to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Respiratory Failure
• Respiratory Insufficiency

Intervention

Drug:
• Insulin
IV insulin titration to target a blood glucose of 80-110 mg/dL
• Insulin
IV insulin titration to target a blood glucose of 150-180 mg/dL

Locations

Country	Name	City	State
Australia	The Royal Children's Hospital	Melbourne	Victoria
Canada	CHU Sainte-Justine	Montreal	Quebec
United States	C.S. Mott Children's Hospital	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Boston Children's Hospital	Boston	Massachusetts
United States	The Children's Hospital at Montefiore	Bronx	New York
United States	Women and Children's Hospital of Buffalo	Buffalo	New York
United States	Ann & Robert H. Lurie Children's Hospital pf Chicago	Chicago	Illinois
United States	University of Chicago Comer Children's Hospital	Chicago	Illinois
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	Children's Medical Center Dallas	Dallas	Texas
United States	Medical City Children's Dallas	Dallas	Texas
United States	Duke Children's Hospital and Medical Center	Durham	North Carolina
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Miller Children's Hospital Long Beach	Long Beach	California
United States	Children's Hospital of Los Angelos	Los Angeles	California
United States	Mattel Children's Hospital	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	Yale-New Haven Children's Hospital	New Haven	Connecticut
United States	North Shore LIJ Cohen Children's Medical Center	New Hyde Park	New York
United States	Morgan Stanley Children's Hospital of New York	New York	New York
United States	Children's Hospital & Research Center of Oakland	Oakland	California
United States	The Children's Hospital at OU Medical Center	Oklahoma City	Oklahoma
United States	Children's Hospital of Orange County	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	St. Louis Children's Hospital	Saint Louis	Missouri
United States	Primary Children's Hospital	Salt Lake City	Utah
United States	UCSF Benioff Children's Hospital	San Francisco	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Westchester Medical Center	Valhalla	New York
United States	Nemours/A.I DuPont Hospital for Children	Wilmington	Delaware

Sponsors (2)

Lead Sponsor	Collaborator
Boston Children's Hospital	National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

References & Publications (1)

Agus MS, Hirshberg E, Srinivasan V, Faustino EV, Luckett PM, Curley MA, Alexander J, Asaro LA, Coughlin-Wells K, Duva D, French J, Hasbani N, Sisko MT, Soto-Rivera CL, Steil G, Wypij D, Nadkarni VM. Design and rationale of Heart and Lung Failure - Pediatric INsulin Titration Trial (HALF-PINT): A randomized clinical trial of tight glycemic control in hyperglycemic critically ill children. Contemp Clin Trials. 2017 Feb;53:178-187. doi: 10.1016/j.cct.2016.12.023. Epub 2016 Dec 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ICU-Free Days	28-day hospital mortality-adjusted ICU length of stay.	Study day 28
Secondary	90-day Hospital Mortality	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.	90 days after randomization
Secondary	28-day Hospital Mortality	We will collect data on 28-day hospital mortality.	28 days after randomization
Secondary	Accumulation of Multiple Organ Dysfunction Syndrome (MODS)	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.	28 days after randomization
Secondary	Ventilator-Free Days	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.	28 days following randomization
Secondary	Developmental Neurobehavioral Outcomes: VABS-II Composite	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.	One year after ICU course
Secondary	Participants With Device-Related or Non-Device Related Nosocomial Infection	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.	Up to 48 hours after ICU discharge
Secondary	Incidence of Catheter-Associated Bloodstream Infection	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.	Up to 48 hours after ICU discharge
Secondary	Incidence of Catheter-Associated Urinary Tract Infection	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.	Up to 48 hours after ICU discharge
Secondary	Incidence of Ventilator-Associated Pneumonia	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.	Up to 48 hours after ICU discharge
Secondary	Incidence of Wound Infection Incidence of Wound Infection	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.	Up to 48 hours after ICU discharge
Secondary	Participants With Severe Hypoglycemia (<40 mg/dL), Unrelated to Insulin Infusion (Insulin Algorithm Safety)	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 will be followed for the duration of ICU stay, an expected average of 8 days
Secondary	Participants With Severe Hypoglycemia (<40 mg/dL), Related to Insulin Infusion (Insulin Algorithm Safety)	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 will be followed for the duration of ICU stay, an expected average of 8 days
Secondary	Participants With Any Hypoglycemia (<60 mg/dL), Unrelated to Insulin Infusion (Insulin Algorithm Safety)	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 will be followed for the duration of ICU stay, an expected average of 8 days
Secondary	Participants With Any Hypoglycemia (<60 mg/dL), Related to Insulin Infusion (Insulin Algorithm Safety)	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 will be followed for the duration of ICU stay, an expected average of 8 days
Secondary	Participants With Hypokalemia (<2.5 mmol/L)	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 will be followed for the duration of ICU stay, an expected average of 8 days
Secondary	Nursing Workload: SWAT (Subjective Workload Assessment Technique) Instrument	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.	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.).
Secondary	Nursing Workload: NASA-TLX (National Aeronautics and Space Administration - Task Load Index) Instrument	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.	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.).
Secondary	Insulin Algorithm Performance: Time to the Target Range	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.	Until study discharge, up to 28 days following randomization
Secondary	Insulin Algorithm Performance: Time in the Target Range	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.	Until study discharge, up to 28 days following randomization
Secondary	Insulin Algorithm Performance: Time-Weighted Glucose Average	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.	Until study discharge, up to 28 days following randomization