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

Boston Children's Hospital

Status and phase: Completed; Phase 3

Conditions: Respiratory Failure; Heart Failure

Treatments: Drug: Insulin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01565941

IRB-P00002310

U01HL107681 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment: 713 patients

Sex: All

Ages: 2 weeks to 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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713 participants in 2 patient groups

Tight Glycemic Control 1 (TGC-1)

Active Comparator group

Description:

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.

Treatment:

Drug: Insulin

Drug: Insulin

Tight Glycemic Control 2 (TGC-2)

Active Comparator group

Description:

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:

Drug: Insulin

Drug: Insulin