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

Michael Sd Agus; Ellie Hirshberg; Vijay Srinivasan; Edward Vincent Faustino; Peter M Luckett; Martha Aq Curley; Jamin Alexander; Lisa A Asaro; Kerry Coughlin-Wells; Donna Duva; Jaclyn French; Natalie Hasbani; Martha T Sisko; Carmen L Soto-Rivera; Garry Steil; David Wypij; Vinay M Nadkarni

doi:10.1016/j.cct.2016.12.023

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.

Authors

Michael Sd Agus¹, Ellie Hirshberg², Vijay Srinivasan³, Edward Vincent Faustino⁴, Peter M Luckett⁵, Martha Aq Curley⁶, Jamin Alexander⁷, Lisa A Asaro⁸, Kerry Coughlin-Wells⁹, Donna Duva¹⁰, Jaclyn French¹¹, Natalie Hasbani¹², Martha T Sisko¹³, Carmen L Soto-Rivera¹⁴, Garry Steil¹⁵, David Wypij¹⁶, Vinay M Nadkarni¹⁷

Affiliations

¹ Boston Children's Hospital Division of Medicine Critical Care, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, United States. Electronic address: [email protected].
² 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: [email protected].
³ The Children's Hospital of Philadelphia, University of Pennsylvania, 3401 Civic Center Blvd., Philadelphia, PA 19104, United States. Electronic address: [email protected].
⁴ Yale-New Haven Children's Hospital, Yale University, 1 Park St., New Haven, CT 06510, United States. Electronic address: [email protected].
⁵ Children's Medical Center Dallas, University of Texas Southwestern, 1935 Medical District Dr., Dallas, TX 75235, United States. Electronic address: [email protected].
⁶ University of Pennsylvania School of Nursing, University of Pennsylvania, 418 Curie Blvd., Philadelphia, PA 19104, United States. Electronic address: [email protected].
⁷ Boston Children's Hospital Division of Medicine Critical Care, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, United States. Electronic address: [email protected].
⁸ Boston Children's Hospital Department of Cardiology, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, United States. Electronic address: [email protected].
⁹ Boston Children's Hospital Division of Medicine Critical Care, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, United States. Electronic address: [email protected].
¹⁰ Boston Children's Hospital Department of Cardiology, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, United States. Electronic address: [email protected].
¹¹ Boston Children's Hospital Division of Medicine Critical Care, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, United States. Electronic address: [email protected].
¹² Boston Children's Hospital Department of Cardiology, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, United States. Electronic address: [email protected].
¹³ The Children's Hospital of Philadelphia, University of Pennsylvania, 3401 Civic Center Blvd., Philadelphia, PA 19104, United States. Electronic address: [email protected].
¹⁴ Boston Children's Hospital Division of Medicine Critical Care, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, United States. Electronic address: [email protected].
¹⁵ Boston Children's Hospital Division of Medicine Critical Care, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, United States. Electronic address: [email protected].
¹⁶ Boston Children's Hospital Department of Cardiology, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, United States. Electronic address: [email protected].
¹⁷ The Children's Hospital of Philadelphia, University of Pennsylvania, 3401 Civic Center Blvd., Philadelphia, PA 19104, United States. Electronic address: [email protected].

Abstract

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 2weeks to 17years receiving inotropic support and/or acute mechanical ventilation, excluding cardiac surgical patients.

Interventions: 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.

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 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.

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT01565941.

Keywords: Insulin therapy; Pediatric critical care; Randomized clinical trial; Stress hyperglycemia.

Publication types

Randomized Controlled Trial
Research Support, N.I.H., Extramural

MeSH terms

Academic Medical Centers
Adolescent
Algorithms
Blood Glucose / metabolism
Cardiotonic Agents / therapeutic use
Child
Child, Preschool
Critical Illness / therapy*
Cross Infection / epidemiology
Disease Management
Female
Heart Failure / complications
Heart Failure / therapy*
Hospital Mortality
Humans
Hyperglycemia / complications
Hyperglycemia / drug therapy*
Hyperglycemia / metabolism
Hypoglycemic Agents / administration & dosage*
Infant
Infant, Newborn
Insulin / administration & dosage*
Intensive Care Units, Pediatric
Length of Stay
Male
Organ Dysfunction Scores
Patient Care Planning
Respiration, Artificial
Respiratory Insufficiency / complications
Respiratory Insufficiency / therapy*

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

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Abstract

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