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

Objectives: Test whether hyperglycemic critically ill children with cardiovascular and/or respiratory failure experience more ICU-free days when assigned to tight glycemic control with a normoglycemic versus hyperglycemic blood glucose target range. Design: Multi-center randomized clinical trial. Setting: Pediatric ICUs at 35 academic hospitals. Patients: Children aged 2 weeks to 17 years receiving inotropic support and/or acute mechanical ventilation, excluding cardiac surgical patients. Interventions: Patients receive intravenous insulin titrated to either 80-110 mg/dL (4.4-6.1 mmol/L) or 150180 mg/dL (8.3-10.0 mmol/L). The intervention begins upon confirmed hyperglycemia and ends when the patient meets study-defined ICU discharge criteria or after 28 days. Continuous glucose monitoring, a minimum glucose infusion, and an explicit insulin infusion algorithm are deployed to achieve the BG targets while minimizing hypoglycemia risk. Measurements and main results: The primary outcome is ICU-free days (equivalent to 28-day hospital mortality adjusted ICU length of stay). Secondary outcomes include 90-day hospital mortality, organ dysfunction scores, ventilator-free days, nosocomial infection rate, neurodevelopmental outcomes, and nursing worldoad. To detect an increase of 125 ICU-free days (corresponding to a 20% relative reduction in 28-day hospital mortality and a one-day reduction in ICU length of stay), 1414 patients are needed for 80% power using a two-sided 0.05 level test. Conclusions: This trial tests whether hyperglycemic critically ill children randomized to 80-110 mg/dL benefit more than those randomized to 150-180 mg/dL. This study implements validated bedside support tools including continuous glucose monitoring and a computerized algorithm to enhance patient safety and ensure reproducible bedside decision-making in achieving glycemic control. (C) 2017 The Authors. Published by Elsevier Inc.