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

This study is currently recruiting participants.
Verified July 2013 by Children's Hospital Boston
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Hospital Boston
ClinicalTrials.gov Identifier:
NCT01565941
First received: March 21, 2012
Last updated: July 29, 2013
Last verified: July 2013
  Purpose

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 >900 critically ill infants and children.


Condition Intervention Phase
Heart Failure
Respiratory Failure
Drug: Insulin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Heart And Lung Failure - Pediatric INsulin Titration Trial (HALF-PINT)

Resource links provided by NLM:


Further study details as provided by Children's Hospital Boston:

Primary Outcome Measures:
  • ICU-Free Days [ Time Frame: Study day 28 ] [ Designated as safety issue: No ]
    28-day hospital mortality-adjusted ICU length of stay


Secondary Outcome Measures:
  • 90-day Hospital Mortality [ Time Frame: 90 days after randomization ] [ Designated as safety issue: No ]
    In order to enable direct comparisons between data gathered in HALF-PINT and the prior adult NICE-SUGAR trial, we will collect data on 90-day hospital mortality.

  • Accumulation of Multiple Organ Dysfunction Syndrome (MODS) [ Time Frame: 28 days after randomization ] [ Designated as safety issue: No ]
    Accumulation of MODS during the 28 days following randomization will be measured. MODS is defined as the concurrent dysfunction of two or more organ systems (e.g., acute lung injury and renal failure). The clinical relevance of MODS as a surrogate outcome measure is well recognized in the intensive care community, and there is a clear relationship between the number of dysfunctional organ systems and the risk of death in critically ill children.

  • Ventilator-Free Days [ Time Frame: 28 days following randomization ] [ Designated as safety issue: No ]
    Ventilator-free days during the 28 days following randomization encompasses both reduction in the duration of ventilation and improvement in mortality. The end of the subject's duration of ventilation is defined as the date/time of extubation for subjects who are intubated, or the date/time of the discontinuation of mechanical ventilation for subjects with tracheostomy.

  • Incidence of Nosocomial Infections [ Time Frame: Up to 48 hours after ICU discharge ] [ Designated as safety issue: No ]
    We will use Centers for Disease Control's (CDC) most recently published definitions for the following nosocomial infections attributable to the ICU stay: total bloodstream infections including Central Venous Line (CVL)-associated bloodstream infections (BSI), respiratory tract infections including ventilator-associated pneumonias, urinary tract infections, and wound infections that occur in the ICU or within 48 hours of discharge to the non-ICU inpatient unit. Device-related infections will be counted per 1,000 device days, and non-device-related infections will be counted per 1,000 ICU days.

  • Insulin Algorithm Safety [ Time Frame: Participants will be followed for the duration of ICU stay, an expected average of 8 days. ] [ Designated as safety issue: Yes ]
    Hypoglycemia will be tracked and reported according to three ranges: severe (SH; <40 mg/dL), moderate (40-49 mg/dL), and mild (50-59 mg/dL) per subject and per subject per insulin day. Lipid activation and metabolic stress during SH will be measured by urgently drawing and sending blood to the local central laboratory for determination of serum glucose, serum triglycerides, free fatty acids, lipoprotein profile, and lactate. As insulin infusion can cause slight changes to serum potassium concentration, hypokalemia <2.5 mmol/L will also be tracked.

  • Developmental neurobehavioral outcomes [ Time Frame: Baseline and 1 year after ICU course ] [ Designated as safety issue: No ]
    Reliable, reproducible measures of adaptive functioning, behavior, and quality of life will be used to determine outcomes at baseline (CBCL, PedsQL) and at one year after ICU discharge (Vineland-II, CBCL, PedsQL). The goal of baseline data collection is to assess pre-ICU health and quality of life.


Estimated Enrollment: 1880
Study Start Date: March 2012
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
Drug: Insulin
IV insulin titration to target a blood glucose of 80-110 mg/dL
Active Comparator: 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.
Drug: Insulin
IV insulin titration to target a blood glucose of 150-180 mg/dL

  Eligibility

Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Cardiovascular failure and/or respiratory failure:

    1. Cardiovascular Failure: Dopamine or dobutamine > 5 mcg/kg/min, or any dose of epinephrine, norepinephrine, milrinone or vasopressin if used to treat hypotension.
    2. Respiratory Failure: Acute mechanical ventilation via endotracheal tube or tracheostomy.
  • Age >= 2 wks 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
  • Diffuse skin disease that does not allow securement of a subcutaneous sensor
  • Therapeutic plan to remain intubated for >28 days
  • Ward of the state
  • Pregnancy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01565941

Contacts
Contact: Michael SD Agus, MD 617 355-6000
Contact: Vinay M Nadkarni, MD 215 590-1000

Locations
United States, California
Children's Hospital of Los Angelos Not yet recruiting
Los Angeles, California, United States, 90027
Contact: Christopher Newth, MD    323-660-2450      
Principal Investigator: Christopher Newth, MD         
United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Peter M Mourani, MD    720-777-1234      
Principal Investigator: Peter Mourani, MD         
Sub-Investigator: Jon Kaufman, MD         
United States, Massachusetts
Children's Hospital Boston Recruiting
Boston, Massachusetts, United States, 02115
Contact: Michael SD Agus, MD    617-355-6000      
Principal Investigator: Michael Agus, MD         
United States, New York
Women and Children's Hospital of Buffalo Not yet recruiting
Buffalo, New York, United States, 14222
Contact: Amanda Hassinger, MD    716-878-1859    albrooks@buffalo.edu   
Principal Investigator: Amanda Hassinger, MD         
Morgan Stanley Children's Hospital of New York Not yet recruiting
New York, New York, United States, 10032
Contact: Katherine Biagas, MD    212-305-8458    kb316@mail.cumc.columbia.edu   
Principal Investigator: Katherine Biagas, MD         
Westchester Medical Center Recruiting
Valhalla, New York, United States, 10595
Contact: Simon Li, MD    914-493-7000      
Principal Investigator: Simon Li, MD         
Principal Investigator: Alan Pinto, MD         
United States, Ohio
Cincinnati Children's Hospital Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Ranjit S Chima, MD    513-636-4200      
Principal Investigator: Ranjit Chima, MD         
United States, Pennsylvania
Penn State Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Neal J Thomas, MD    717-531-8080      
Principal Investigator: Neal Thomas, MD         
Sub-Investigator: Robert Tamburro, MD         
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Vijay Srinivasan, MD    215-590-1000      
Principal Investigator: Vijay Srinivasan, MD         
Sub-Investigator: Lauren Marsillio, MD         
Sponsors and Collaborators
Children's Hospital Boston
Investigators
Principal Investigator: Michael SD Agus, MD Children's Hospital Boston
Principal Investigator: Vinay M Nadkarni, MD Children's Hospital of Philadelphia
  More Information

No publications provided

Responsible Party: Children's Hospital Boston
ClinicalTrials.gov Identifier: NCT01565941     History of Changes
Other Study ID Numbers: IRB-P00002310, U01HL107681
Study First Received: March 21, 2012
Last Updated: July 29, 2013
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by Children's Hospital Boston:
Cardiovascular
Respiratory
Failure
Heart
Lung
Continuous glucose monitoring
Tight glycemic control
Subcutaneous
Insulin
Algorithm

Additional relevant MeSH terms:
Heart Failure
Respiratory Insufficiency
Heart Diseases
Cardiovascular Diseases
Respiration Disorders
Respiratory Tract Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 23, 2014