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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01565941




Registration number
NCT01565941
Ethics application status
Date submitted
21/03/2012
Date registered
29/03/2012
Date last updated
9/07/2019

Titles & IDs
Public title
Heart And Lung Failure - Pediatric INsulin Titration Trial
Scientific title
Heart And Lung Failure - Pediatric INsulin Titration Trial (HALF-PINT)
Secondary ID [1] 0 0
U01HL107681
Secondary ID [2] 0 0
IRB-P00002310
Universal Trial Number (UTN)
Trial acronym
HALF-PINT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart Failure 0 0
Respiratory Failure 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Insulin
Treatment: Drugs - Insulin

Active Comparator: Tight Glycemic Control 1 (TGC-1) - Approximately half of the subjects randomized into HALF-PINT will be randomized into TGC-1 which will seek to maintain the subject's blood sugar between 80-110 mg/dL. Intravenous insulin may be administered per insulin algorithm.

Active Comparator: Tight Glycemic Control 2 (TGC-2) - Approximately half of the subjects randomized into HALF-PINT will be randomized into TGC-2 which will seek to maintain the subject's blood sugar between 150-180 mg/dL. Intravenous insulin may be administered per insulin algorithm.


Treatment: Drugs: Insulin
IV insulin titration to target a blood glucose of 80-110 mg/dL

Treatment: Drugs: Insulin
IV insulin titration to target a blood glucose of 150-180 mg/dL

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
ICU-Free Days - 28-day hospital mortality-adjusted ICU length of stay.
Timepoint [1] 0 0
Study day 28
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
90 days after randomization
Secondary outcome [2] 0 0
28-day Hospital Mortality - We will collect data on 28-day hospital mortality.
Timepoint [2] 0 0
28 days after randomization
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
28 days after randomization
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
28 days following randomization
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
One year after ICU course
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Up to 48 hours after ICU discharge
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
Up to 48 hours after ICU discharge
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
Up to 48 hours after ICU discharge
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
Up to 48 hours after ICU discharge
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
Up to 48 hours after ICU discharge
Secondary outcome [11] 0 0
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.
Timepoint [11] 0 0
Participants will be followed for the duration of ICU stay, an expected average of 8 days
Secondary outcome [12] 0 0
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.
Timepoint [12] 0 0
Participants will be followed for the duration of ICU stay, an expected average of 8 days
Secondary outcome [13] 0 0
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.
Timepoint [13] 0 0
Participants will be followed for the duration of ICU stay, an expected average of 8 days
Secondary outcome [14] 0 0
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.
Timepoint [14] 0 0
Participants will be followed for the duration of ICU stay, an expected average of 8 days
Secondary outcome [15] 0 0
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.
Timepoint [15] 0 0
Participants will be followed for the duration of ICU stay, an expected average of 8 days
Secondary outcome [16] 0 0
Nursing Workload - 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. Nurses' perceptions of their capacity to complete both TGC-related and non TGC-related nursing activities over several intervals of the study period will be described via qualitative and summary statistics.
Timepoint [16] 0 0
Multiple intervals during the study period
Secondary outcome [17] 0 0
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.
Timepoint [17] 0 0
Until study discharge, up to 28 days following randomization
Secondary outcome [18] 0 0
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.
Timepoint [18] 0 0
Until study discharge, up to 28 days following randomization
Secondary outcome [19] 0 0
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.
Timepoint [19] 0 0
Until study discharge, up to 28 days following randomization

Eligibility
Key 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)
Minimum age
No limit
Maximum age
17 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
The Royal Children's Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3052 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Delaware
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Kentucky
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
New Hampshire
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Oklahoma
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Utah
Country [20] 0 0
United States of America
State/province [20] 0 0
Washington
Country [21] 0 0
Canada
State/province [21] 0 0
Quebec

Funding & Sponsors
Primary sponsor type
Other
Name
Boston Children’s Hospital
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Heart, Lung, and Blood Institute (NHLBI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01565941
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Michael SD Agus, MD
Address 0 0
Boston Children’s Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications