Heart And Lung Failure - Pediatric INsulin Titration Trial
Condition: Heart Failure; Respiratory Failure
MeSH terms: Respiratory Insufficiency
Intervention: Insulin; Insulin
Intervention description: IV insulin titration to target a blood glucose of 80-110 mg/dL; IV insulin titration to target a blood glucose of 150-180 mg/dL
Intervention MeSH terms: Insulin; Insulin, Globin Zinc
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 713.0
Sex: All
Minimum age: 2 Weeks
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Cardiovascular; Respiratory; Failure; Heart; Lung; Continuous glucose monitoring; Tight glycemic control; Subcutaneous; Insulin; Algorithm

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