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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT01565941
Ethics application status
Date submitted
21/03/2012
Date registered
29/03/2012
Date last updated
25/07/2022

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
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
Timepoint [1] 0 0
Study day 28
Secondary outcome [1] 0 0
90-day Hospital Mortality
Timepoint [1] 0 0
90 days after randomization
Secondary outcome [2] 0 0
28-day Hospital Mortality
Timepoint [2] 0 0
28 days after randomization
Secondary outcome [3] 0 0
Accumulation of Multiple Organ Dysfunction Syndrome (MODS)
Timepoint [3] 0 0
28 days after randomization
Secondary outcome [4] 0 0
Ventilator-Free Days
Timepoint [4] 0 0
28 days following randomization
Secondary outcome [5] 0 0
Developmental Neurobehavioral Outcomes: VABS-II Composite
Timepoint [5] 0 0
One year after ICU course
Secondary outcome [6] 0 0
Participants With Device-Related or Non-Device Related Nosocomial Infection
Timepoint [6] 0 0
Up to 48 hours after ICU discharge
Secondary outcome [7] 0 0
Incidence of Catheter-Associated Bloodstream Infection
Timepoint [7] 0 0
Up to 48 hours after ICU discharge
Secondary outcome [8] 0 0
Incidence of Catheter-Associated Urinary Tract Infection
Timepoint [8] 0 0
Up to 48 hours after ICU discharge
Secondary outcome [9] 0 0
Incidence of Ventilator-Associated Pneumonia
Timepoint [9] 0 0
Up to 48 hours after ICU discharge
Secondary outcome [10] 0 0
Incidence of Wound Infection Incidence of Wound Infection
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)
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)
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)
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)
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)
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: SWAT (Subjective Workload Assessment Technique) Instrument
Timepoint [16] 0 0
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 outcome [17] 0 0
Nursing Workload: NASA-TLX (National Aeronautics and Space Administration - Task Load Index) Instrument
Timepoint [17] 0 0
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 outcome [18] 0 0
Insulin Algorithm Performance: Time to the Target Range
Timepoint [18] 0 0
Until study discharge, up to 28 days following randomization
Secondary outcome [19] 0 0
Insulin Algorithm Performance: Time in the Target Range
Timepoint [19] 0 0
Until study discharge, up to 28 days following randomization
Secondary outcome [20] 0 0
Insulin Algorithm Performance: Time-Weighted Glucose Average
Timepoint [20] 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
2 Weeks
Maximum age
17 Years
Sex
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
1/04/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2018
Sample size
Target
Accrual to date
Final
713
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/study/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.
Hirshberg EL, Alexander JL, Asaro LA, Coughlin-Wells K, Steil GM, Spear D, Stone C, Nadkarni VM, Agus MSD; HALF-PINT Study Investigators. Performance of an Electronic Decision Support System as a Therapeutic Intervention During a Multicenter PICU Clinical Trial: Heart and Lung Failure-Pediatric Insulin Titration Trial (HALF-PINT). Chest. 2021 Sep;160(3):919-928. doi: 10.1016/j.chest.2021.04.049. Epub 2021 Apr 29.
LaMarra D, French J, Bailey C, Sisko MT, Coughlin-Wells K, Agus MSD, Srinivasan V, Nadkarni VM; Heart And Lung Failure-Pediatric INsulin Titration (HALF-PINT) Study Investigators. A Novel Framework Using Remote Telesimulation With Standardized Parents to Improve Research Staff Preparedness for Informed Consent in Pediatric Critical Care Research. Pediatr Crit Care Med. 2020 Dec;21(12):e1042-e1051. doi: 10.1097/PCC.0000000000002484.
Biagas KV, Hinton VJ, Hasbani NR, Luckett PM, Wypij D, Nadkarni VM, Agus MSD; HALF-PINT trial study investigators; PALISI Network. Long-Term Neurobehavioral and Quality of Life Outcomes of Critically Ill Children after Glycemic Control. J Pediatr. 2020 Mar;218:57-63.e5. doi: 10.1016/j.jpeds.2019.10.055. Epub 2020 Jan 3.
Srinivasan V, Hasbani NR, Mehta NM, Irving SY, Kandil SB, Allen HC, Typpo KV, Cvijanovich NZ, Faustino EVS, Wypij D, Agus MSD, Nadkarni VM; Heart and Lung Failure-Pediatric Insulin Titration (HALF-PINT) Study Investigators. Early Enteral Nutrition Is Associated With Improved Clinical Outcomes in Critically Ill Children: A Secondary Analysis of Nutrition Support in the Heart and Lung Failure-Pediatric Insulin Titration Trial. Pediatr Crit Care Med. 2020 Mar;21(3):213-221. doi: 10.1097/PCC.0000000000002135.
Agus MS, Wypij D, Hirshberg EL, Srinivasan V, Faustino EV, Luckett PM, Alexander JL, Asaro LA, Curley MA, Steil GM, Nadkarni VM; HALF-PINT Study Investigators and the PALISI Network. Tight Glycemic Control in Critically Ill Children. N Engl J Med. 2017 Feb 23;376(8):729-741. doi: 10.1056/NEJMoa1612348. Epub 2017 Jan 24.
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01565941