title: 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.
abstract: 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.
  
  
  
  Multi-center randomized clinical trial.
  
  
  
  Pediatric ICUs at 35 academic hospitals.
  
  
  
  Children aged 2weeks to 17years receiving inotropic support and/or acute mechanical ventilation, excluding cardiac surgical patients.
  
  
  
  Patients receive intravenous insulin titrated to either 80-110mg/dL (4.4-6.1mmol/L) or 150-180mg/dL (8.3-10.0mmol/L). The intervention begins upon confirmed hyperglycemia and ends when the patient meets study-defined ICU discharge criteria or after 28days. Continuous glucose monitoring, a minimum glucose infusion, and an explicit insulin infusion algorithm are deployed to achieve the BG targets while minimizing hypoglycemia risk.
  
  
  
  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 workload. To detect an increase of 1.25 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.
  
  
  
  This trial tests whether hyperglycemic critically ill children randomized to 80-110mg/dL benefit more than those randomized to 150-180mg/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.
authors.affiliation: Boston Children's Hospital Division of Medicine Critical Care, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, United States. Electronic address: michael.agus@childrens.harvard.edu.
authors.forename: Michael Sd
authors.initials: MS
authors.lastname: Agus
authors.affiliation: Intermountain Medical Center Division of Pulmonary and Critical Care, University of Utah, 100 Mario Capecchi Dr., Salt Lake City, UT 84132, United States. Electronic address: ellie.hirshberg@hsc.utah.edu.
authors.forename: Ellie
authors.initials: E
authors.lastname: Hirshberg
authors.affiliation: The Children's Hospital of Philadelphia, University of Pennsylvania, 3401 Civic Center Blvd., Philadelphia, PA 19104, United States. Electronic address: srinivasan@email.chop.edu.
authors.forename: Vijay
authors.initials: V
authors.lastname: Srinivasan
authors.affiliation: Yale-New Haven Children's Hospital, Yale University, 1 Park St., New Haven, CT 06510, United States. Electronic address: vince.faustino@yale.edu.
authors.forename: Edward Vincent
authors.initials: EV
authors.lastname: Faustino
authors.affiliation: Children's Medical Center Dallas, University of Texas Southwestern, 1935 Medical District Dr., Dallas, TX 75235, United States. Electronic address: peter.luckett@childrens.com.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Luckett
authors.affiliation: University of Pennsylvania School of Nursing, University of Pennsylvania, 418 Curie Blvd., Philadelphia, PA 19104, United States. Electronic address: curley@nursing.upenn.edu.
authors.forename: Martha Aq
authors.initials: MA
authors.lastname: Curley
authors.affiliation: Boston Children's Hospital Division of Medicine Critical Care, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, United States. Electronic address: jamin.alexander@childrens.harvard.edu.
authors.forename: Jamin
authors.initials: J
authors.lastname: Alexander
authors.affiliation: Boston Children's Hospital Department of Cardiology, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, United States. Electronic address: lisa.asaro@cardio.chboston.org.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Asaro
authors.affiliation: Boston Children's Hospital Division of Medicine Critical Care, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, United States. Electronic address: kerry.coughlin-wells@childrens.harvard.edu.
authors.forename: Kerry
authors.initials: K
authors.lastname: Coughlin-Wells
authors.affiliation: Boston Children's Hospital Department of Cardiology, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, United States. Electronic address: donna.duva@cardio.chboston.org.
authors.forename: Donna
authors.initials: D
authors.lastname: Duva
authors.affiliation: Boston Children's Hospital Division of Medicine Critical Care, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, United States. Electronic address: jaclyn.french@childrens.harvard.edu.
authors.forename: Jaclyn
authors.initials: J
authors.lastname: French
authors.affiliation: Boston Children's Hospital Department of Cardiology, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, United States. Electronic address: natalie.hasbani@childrens.harvard.edu.
authors.forename: Natalie
authors.initials: N
authors.lastname: Hasbani
authors.affiliation: The Children's Hospital of Philadelphia, University of Pennsylvania, 3401 Civic Center Blvd., Philadelphia, PA 19104, United States. Electronic address: siskom@email.chop.edu.
authors.forename: Martha T
authors.initials: MT
authors.lastname: Sisko
authors.affiliation: Boston Children's Hospital Division of Medicine Critical Care, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, United States. Electronic address: carmen.soto@childrens.harvard.edu.
authors.forename: Carmen L
authors.initials: CL
authors.lastname: Soto-Rivera
authors.affiliation: Boston Children's Hospital Division of Medicine Critical Care, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, United States. Electronic address: garry.steil@childrens.harvard.edu.
authors.forename: Garry
authors.initials: G
authors.lastname: Steil
authors.affiliation: Boston Children's Hospital Department of Cardiology, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, United States. Electronic address: david.wypij@cardio.chboston.org.
authors.forename: David
authors.initials: D
authors.lastname: Wypij
authors.affiliation: The Children's Hospital of Philadelphia, University of Pennsylvania, 3401 Civic Center Blvd., Philadelphia, PA 19104, United States. Electronic address: nadkarni@email.chop.edu.
authors.forename: Vinay M
authors.initials: VM
authors.lastname: Nadkarni
mesh_terms: D000046:Academic Medical Centers; D000293:Adolescent; D000465:Algorithms; D001786:Blood Glucose / Q000378:metabolism; D002316:Cardiotonic Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D016638:Critical Illness / Q000628:therapy*; D003428:Cross Infection / Q000453:epidemiology; D019468:Disease Management; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000628:therapy*; D017052:Hospital Mortality; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007223:Infant; D007231:Infant, Newborn; D007328:Insulin / Q000008:administration & dosage*; D015278:Intensive Care Units, Pediatric; D007902:Length of Stay; D008297:Male; D063305:Organ Dysfunction Scores; D010347:Patient Care Planning; D012121:Respiration, Artificial; D012131:Respiratory Insufficiency / Q000150:complications / Q000628:therapy*
chemical_list: D001786:Blood Glucose; D002316:Cardiotonic Agents; D007004:Hypoglycemic Agents; D007328:Insulin
keywords: Insulin therapy; Pediatric critical care; Randomized clinical trial; Stress hyperglycemia