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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 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 23, 2014
Last verified: July 2014
  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.

  • Nursing Workload [ Time Frame: Multiple intervals during the study period. ] [ Designated as safety issue: No ]
    The cognitive burden placed upon bedside nurses when managing a patient on TGC will be described. Bedside nurses will be randomly selected to complete an anonymous survey describing their perceptions of workload burden associated with managing a patient on TGC. Nurses' perceptions of their capacity to complete both TGC‐related and non TGC-related nursing activities over several intervals of the study period will be described via qualitative and summary statistics.


Estimated Enrollment: 1880
Study Start Date: March 2012
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: July 2018 (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. Intravenous insulin may be administered per insulin algorithm.
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. Intravenous insulin may be administered per insulin algorithm.
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
  • Receiving therapeutic cooling with targeted body temperatures <34 degrees Celsius
  • Current or planned ketogenic diet
  • Ward of the state
  • Pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 34 Study Locations
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

Additional 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 23, 2014
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
Respiratory Tract Diseases
Cardiovascular Diseases
Heart Diseases
Respiration Disorders
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014