Heart And Lung Failure - Pediatric INsulin Titration Trial

NCT ID: NCT01565941

Last Updated: 2022-07-25

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

713 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-04-30

Study Completion Date

2018-02-28

Brief Summary

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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.

Detailed Description

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Conditions

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Heart Failure Respiratory Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Tight Glycemic Control 1 (TGC-1)

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.

Group Type ACTIVE_COMPARATOR

Insulin

Intervention Type DRUG

IV insulin titration to target a blood glucose of 80-110 mg/dL

Tight Glycemic Control 2 (TGC-2)

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.

Group Type ACTIVE_COMPARATOR

Insulin

Intervention Type DRUG

IV insulin titration to target a blood glucose of 150-180 mg/dL

Interventions

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Insulin

IV insulin titration to target a blood glucose of 80-110 mg/dL

Intervention Type DRUG

Insulin

IV insulin titration to target a blood glucose of 150-180 mg/dL

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

2 Weeks

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Boston Children's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Michael Agus

Associate Professor of Pediatrics, Harvard Medical School

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Michael SD Agus, MD

Role: PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Vinay M Nadkarni, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

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Miller Children's Hospital Long Beach

Long Beach, California, United States

Site Status

Children's Hospital of Los Angelos

Los Angeles, California, United States

Site Status

Mattel Children's Hospital

Los Angeles, California, United States

Site Status

Children's Hospital & Research Center of Oakland

Oakland, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

UCSF Benioff Children's Hospital

San Francisco, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Yale-New Haven Children's Hospital

New Haven, Connecticut, United States

Site Status

Nemours/A.I DuPont Hospital for Children

Wilmington, Delaware, United States

Site Status

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Site Status

Ann & Robert H. Lurie Children's Hospital pf Chicago

Chicago, Illinois, United States

Site Status

University of Chicago Comer Children's Hospital

Chicago, Illinois, United States

Site Status

University of Louisville

Louisville, Kentucky, United States

Site Status

University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

C.S. Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status

St. Louis Children's Hospital

St Louis, Missouri, United States

Site Status

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Women and Children's Hospital of Buffalo

Buffalo, New York, United States

Site Status

North Shore LIJ Cohen Children's Medical Center

New Hyde Park, New York, United States

Site Status

Morgan Stanley Children's Hospital of New York

New York, New York, United States

Site Status

The Children's Hospital at Montefiore

The Bronx, New York, United States

Site Status

Westchester Medical Center

Valhalla, New York, United States

Site Status

Duke Children's Hospital and Medical Center

Durham, North Carolina, United States

Site Status

Cincinnati Children's Hospital

Cincinnati, Ohio, United States

Site Status

The Children's Hospital at OU Medical Center

Oklahoma City, Oklahoma, United States

Site Status

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Medical City Children's Dallas

Dallas, Texas, United States

Site Status

Children's Medical Center Dallas

Dallas, Texas, United States

Site Status

Primary Children's Hospital

Salt Lake City, Utah, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

The Royal Children's Hospital

Melbourne, Victoria, Australia

Site Status

CHU Sainte-Justine

Montreal, Quebec, Canada

Site Status

Countries

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United States Australia Canada

References

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Agus MS, Hirshberg E, Srinivasan V, Faustino EV, Luckett PM, Curley MA, Alexander J, Asaro LA, Coughlin-Wells K, Duva D, French J, Hasbani N, Sisko MT, Soto-Rivera CL, Steil G, Wypij D, Nadkarni VM. 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.

Reference Type BACKGROUND
PMID: 28042054 (View on PubMed)

LaRovere KL, Asaro LA, Coughlin-Wells K, Nadkarni VM, Agus MSD; Heart and Lung Failure-Pediatric Insulin Titration (HALF-PINT) Study Investigators. Blood Glucose Range for Hyperglycemic PICU Children With Primary Neurologic Diagnoses: Analysis of the Heart and Lung Failure-Pediatric Insulin Titration (HALF-PINT) Trial. Pediatr Crit Care Med. 2025 Apr 1;26(4):e432-e446. doi: 10.1097/PCC.0000000000003689. Epub 2025 Feb 5.

Reference Type DERIVED
PMID: 39907523 (View on PubMed)

Yang JO, Zinter MS, Pellegrini M, Wong MY, Gala K, Markovic D, Nadel B, Peng K, Do N, Mangul S, Nadkarni VM, Karlsberg A, Deshpande D, Butte MJ, Asaro L, Agus M, Sapru A; Study Site Investigators for CAF-PINT. Whole blood transcriptomics identifies subclasses of pediatric septic shock. Crit Care. 2023 Dec 8;27(1):486. doi: 10.1186/s13054-023-04689-y.

Reference Type DERIVED
PMID: 38066613 (View on PubMed)

Yang JO, Zinter MS, Pellegrini M, Wong MY, Gala K, Markovic D, Nadel B, Peng K, Do N, Mangul S, Nadkarni VM, Karlsberg A, Deshpande D, Butte MJ, Asaro L, Agus M, Sapru A. Whole Blood Transcriptomics Identifies Subclasses of Pediatric Septic Shock. Res Sq [Preprint]. 2023 Aug 28:rs.3.rs-3267057. doi: 10.21203/rs.3.rs-3267057/v1.

Reference Type DERIVED
PMID: 37693502 (View on PubMed)

Bellon F, Sola I, Gimenez-Perez G, Hernandez M, Metzendorf MI, Rubinat E, Mauricio D. Perioperative glycaemic control for people with diabetes undergoing surgery. Cochrane Database Syst Rev. 2023 Aug 1;8(8):CD007315. doi: 10.1002/14651858.CD007315.pub3.

Reference Type DERIVED
PMID: 37526194 (View on PubMed)

Zinter MS, Markovic D, Asaro LA, Nadkarni VM, McQuillen PS, Sinha P, Matthay MA, Jeschke MG, Agus MSD, Sapru A; CAF-PINT Investigators of the PALISI Network. Tight Glycemic Control, Inflammation, and the ICU: Evidence for Heterogeneous Treatment Effects in Two Randomized Controlled Trials. Am J Respir Crit Care Med. 2023 Apr 1;207(7):945-949. doi: 10.1164/rccm.202210-1988LE. No abstract available.

Reference Type DERIVED
PMID: 36656551 (View on PubMed)

Hirshberg EL, Alexander JL, Asaro LA, Coughlin-Wells K, Steil GM, Spear D, Stone C, Nadkarni VM, Agus MSD; HALF-PINT Study Investigators. Performance of an Electronic Decision Support System as a Therapeutic Intervention During a Multicenter PICU Clinical Trial: Heart and Lung Failure-Pediatric Insulin Titration Trial (HALF-PINT). Chest. 2021 Sep;160(3):919-928. doi: 10.1016/j.chest.2021.04.049. Epub 2021 Apr 29.

Reference Type DERIVED
PMID: 33932465 (View on PubMed)

LaMarra D, French J, Bailey C, Sisko MT, Coughlin-Wells K, Agus MSD, Srinivasan V, Nadkarni VM; Heart And Lung Failure-Pediatric INsulin Titration (HALF-PINT) Study Investigators. A Novel Framework Using Remote Telesimulation With Standardized Parents to Improve Research Staff Preparedness for Informed Consent in Pediatric Critical Care Research. Pediatr Crit Care Med. 2020 Dec;21(12):e1042-e1051. doi: 10.1097/PCC.0000000000002484.

Reference Type DERIVED
PMID: 32740181 (View on PubMed)

Biagas KV, Hinton VJ, Hasbani NR, Luckett PM, Wypij D, Nadkarni VM, Agus MSD; HALF-PINT trial study investigators; PALISI Network. Long-Term Neurobehavioral and Quality of Life Outcomes of Critically Ill Children after Glycemic Control. J Pediatr. 2020 Mar;218:57-63.e5. doi: 10.1016/j.jpeds.2019.10.055. Epub 2020 Jan 3.

Reference Type DERIVED
PMID: 31910992 (View on PubMed)

Srinivasan V, Hasbani NR, Mehta NM, Irving SY, Kandil SB, Allen HC, Typpo KV, Cvijanovich NZ, Faustino EVS, Wypij D, Agus MSD, Nadkarni VM; Heart and Lung Failure-Pediatric Insulin Titration (HALF-PINT) Study Investigators. Early Enteral Nutrition Is Associated With Improved Clinical Outcomes in Critically Ill Children: A Secondary Analysis of Nutrition Support in the Heart and Lung Failure-Pediatric Insulin Titration Trial. Pediatr Crit Care Med. 2020 Mar;21(3):213-221. doi: 10.1097/PCC.0000000000002135.

Reference Type DERIVED
PMID: 31577692 (View on PubMed)

Agus MS, Wypij D, Hirshberg EL, Srinivasan V, Faustino EV, Luckett PM, Alexander JL, Asaro LA, Curley MA, Steil GM, Nadkarni VM; HALF-PINT Study Investigators and the PALISI Network. Tight Glycemic Control in Critically Ill Children. N Engl J Med. 2017 Feb 23;376(8):729-741. doi: 10.1056/NEJMoa1612348. Epub 2017 Jan 24.

Reference Type DERIVED
PMID: 28118549 (View on PubMed)

Other Identifiers

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U01HL107681

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB-P00002310

Identifier Type: -

Identifier Source: org_study_id

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