Clinical trial NCT01565941: Heart And Lung Failure - Pediatric INsulin Titration Trial
Official title: Heart And Lung Failure - Pediatric INsulin Titration Trial (HALF-PINT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Heart Failure
Respiratory Failure
Keywords: Cardiovascular
Respiratory
Failure
Heart
Lung
Continuous glucose monitoring
Tight glycemic control
Subcutaneous
Insulin
Algorithm
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2012-03-29
Enrollment: 713
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: ICU-Free Days
timeFrame: Study day 28
Secondary outcomes:
measure: 90-day Hospital Mortality
timeFrame: 90 days after randomization
measure: 28-day Hospital Mortality
timeFrame: 28 days after randomization
measure: Accumulation of Multiple Organ Dysfunction Syndrome (MODS)
timeFrame: 28 days after randomization
measure: Ventilator-Free Days
timeFrame: 28 days following randomization
measure: Developmental Neurobehavioral Outcomes: VABS-II Composite
timeFrame: One year after ICU course
measure: Participants With Device-Related or Non-Device Related Nosocomial Infection
timeFrame: Up to 48 hours after ICU discharge
measure: Incidence of Catheter-Associated Bloodstream Infection
timeFrame: Up to 48 hours after ICU discharge
measure: Incidence of Catheter-Associated Urinary Tract Infection
timeFrame: Up to 48 hours after ICU discharge
measure: Incidence of Ventilator-Associated Pneumonia
timeFrame: Up to 48 hours after ICU discharge
measure: Incidence of Wound Infection Incidence of Wound Infection
timeFrame: Up to 48 hours after ICU discharge
measure: Participants With Severe Hypoglycemia (<40 mg/dL), Unrelated to Insulin Infusion (Insulin Algorithm Safety)
timeFrame: Participants will be followed for the duration of ICU stay, an expected average of 8 days
measure: Participants With Severe Hypoglycemia (<40 mg/dL), Related to Insulin Infusion (Insulin Algorithm Safety)
timeFrame: Participants will be followed for the duration of ICU stay, an expected average of 8 days
measure: Participants With Any Hypoglycemia (<60 mg/dL), Unrelated to Insulin Infusion (Insulin Algorithm Safety)
timeFrame: Participants will be followed for the duration of ICU stay, an expected average of 8 days
measure: Participants With Any Hypoglycemia (<60 mg/dL), Related to Insulin Infusion (Insulin Algorithm Safety)
timeFrame: Participants will be followed for the duration of ICU stay, an expected average of 8 days
measure: Participants With Hypokalemia (<2.5 mmol/L)
timeFrame: Participants will be followed for the duration of ICU stay, an expected average of 8 days
measure: Nursing Workload: SWAT (Subjective Workload Assessment Technique) Instrument
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.).
measure: Nursing Workload: NASA-TLX (National Aeronautics and Space Administration - Task Load Index) Instrument
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.).
measure: Insulin Algorithm Performance: Time to the Target Range
timeFrame: Until study discharge, up to 28 days following randomization
measure: Insulin Algorithm Performance: Time in the Target Range
timeFrame: Until study discharge, up to 28 days following randomization
measure: Insulin Algorithm Performance: Time-Weighted Glucose Average
timeFrame: Until study discharge, up to 28 days following randomization
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Miller Children's Hospital Long Beach
state: California
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angelos
state: California
city: Los Angeles
country: United States
facility: Mattel Children's Hospital
state: California
city: Oakland
country: United States
facility: Children's Hospital & Research Center of Oakland
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Francisco
country: United States
facility: UCSF Benioff Children's Hospital
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale-New Haven Children's Hospital
state: Connecticut
city: Wilmington
country: United States
facility: Nemours/A.I DuPont Hospital for Children
state: Delaware
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital pf Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comer Children's Hospital
state: Illinois
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital
state: Michigan
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Bronx
country: United States
facility: The Children's Hospital at Montefiore
state: New York
city: Buffalo
country: United States
facility: Women and Children's Hospital of Buffalo
state: New York
city: New Hyde Park
country: United States
facility: North Shore LIJ Cohen Children's Medical Center
state: New York
city: New York
country: United States
facility: Morgan Stanley Children's Hospital of New York
state: New York
city: Valhalla
country: United States
facility: Westchester Medical Center
state: New York
city: Durham
country: United States
facility: Duke Children's Hospital and Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: The Children's Hospital at OU Medical Center
state: Oklahoma
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Dallas
country: United States
facility: Medical City Children's Dallas
state: Texas
city: Dallas
country: United States
facility: Children's Medical Center Dallas
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Melbourne
country: Australia
facility: The Royal Children's Hospital
state: Victoria
city: Montreal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
Study officials:
affiliation: Boston Children's Hospital
name: Michael SD Agus, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Philadelphia
name: Vinay M Nadkarni, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.