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Coagulation and Fibrinolysis in Pediatric Insulin Titration Trial (CAF-PINT)

Sponsor
University of California, San Francisco (Other)
Overall Status
Completed
CT.gov ID
NCT01892969
Collaborator
National Heart, Lung, and Blood Institute (NHLBI) (NIH)
304
Enrollment
25
Locations
47
Duration (Months)
12.2
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Project Summary We propose an ancillary study to The Heart and Lung Failure Pediatric Insulin Titration trial (HALF PINT), which is investigating the impact of normalizing blood glucose using insulin infusions on clinical outcomes among children with hyperglycemia and heart and lung failure. In this ancillary study, we will measure plasma levels of inflammatory, coagulation, and fibrinolysis proteins and genotype DNA for polymorphisms among patients enrolled in the HALF PINT trial. The results from this ancillary study will help us to understand potential mechanisms through which normalizing blood glucose provides benefit, which may lead to development of new therapeutic strategies in critically ill children

Condition or Disease Intervention/Treatment Phase

    Detailed Description

    ABSTRACT Hyperglycemia occurs frequently among critically ill children and is associated with increased morbidity and mortality. Approximately 25% of critically ill children with heart and lung failure (i.e., those receiving mechanical ventilation and/or inotropes) develop hyperglycemia within 24 hours of admission, and if the hyperglycemia is sustained (lasting for > 50% of PICU stay), it results in a 6-fold increase in the odds of mortality. Previous studies have demonstrated that tight glycemic control with insulin, aimed at achieving normoglycemia (TGC-NL) can result in improvement in mortality and morbidity in selected groups of critically ill patients with hyperglycemia. However, the precise mechanism by which TGC-NL leads to improvement in morbidity and mortality is not known. Hyperglycemia is known to result in a pro-thrombotic state via activation of coagulation and impairment of fibrinolysis. This pro-thrombotic, anti-fibrinolytic state, may lead to intravascular fibrin deposition and micro thrombi, which can be a key contributor to the pathogenesis of multi-organ failure. We propose to take advantage of The Heart and Lung Failure Pediatric Insulin Titration trial (HALF PINT) - an NHLBI-funded randomized, controlled trial designed to study the impact of TGC-NL on clinical outcomes among children with heart and lung failure

    • to investigate the effect of TGC-NL on inflammation, fibrinolysis, and coagulation and to determine the extent to which improvement in deranged coagulation and fibrinolysis by TGC-NL contributes to improvement in clinical outcomes. We propose to enroll 800 critically ill patients with hyperglycemia and heart and lung failure from the HALF PINT study. Since the parent trial will not collect any blood samples other than for confirmation of blood glucose, we will approach parents or surrogates of children enrolled in the HALF PINT trial and obtain informed consent for participation in this ancillary study. We will collect blood samples (3cc from children 2 years and younger, and 5ml from children 3 years and older) at Days 1, 3, and 5 after randomization. We will measure plasma levels of selected markers of coagulation and fibrinolysis and genotype DNA for polymorphisms in the corresponding genes. We will correlate changes over time in the biomarkers with allocation to treatment arm to test whether the beneficial effects of TGC-NL are achieved via normalization of coagulation and fibrinolysis. We will also genotype for tag SNPs in the corresponding genes and test for association of the plasma and genetic markers with clinical outcomes. The results from this study will provide mechanistic insights into the effect of TGC-NL on clinical outcome and could lead to the use of anti-inflammatory, anti-coagulant or pro-fibrinolytic agents as adjunctive therapies among select groups of critically ill children with hyperglycemia who may not be amenable to tight glucose control or are at higher risk of adverse clinical outcomes from a pro thrombotic environment. Results from this study may lead to identification of protein or genetic markers that will identify critically ill children most likely to benefit from existing anticoagulant therapies such as activated protein C.

    Study Design

    Study Type:
    Observational
    Actual Enrollment :
    304 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Official Title:
    Coagulation and Fibrinolysis in a Pediatric Insulin Titration Trial
    Study Start Date :
    Oct 1, 2012
    Actual Primary Completion Date :
    Sep 1, 2016
    Actual Study Completion Date :
    Sep 1, 2016

    Arms and Interventions

    Arm Intervention/Treatment
    HEART AND LUNG FAILURE

    Patients with Heart failure or Respiratory Failure with Hyperglycemia

    Outcome Measures

    Primary Outcome Measures

    1. Biomarkers of Thrombosis and Inflammation (Interleukin 6 (IL6) and Interleukin 8 (IL8) , Plasminogen Activator Inhibitor -1 (PAI-1)) [4 days]

      The researchers will measure IL-6, IL-8 and PAI-1 on patient plasma using a Luminex based multiplex array. All measurements are in pg/mL. The Slope of change in biomarkers from the time of start of insulin infusion to 2 and 4 days after start of insulin infusion will be used as the outcome measure.

    Secondary Outcome Measures

    1. Number of participants with Development of Acute Lung Injury (ALI) [28 days]

      Acute Lung Injury (ALI) measured as hypoxemia with bilateral infiltrates

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    14 Days to 18 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    All Patients enrolled in the HALF PINT trial

    Exclusion Criteria:

    Bleeding Diathesis as manifest by a Most Recent recorded International Normalized ratio (INR) >3

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Children's Hospital of Los Angeles Los Angeles California United States 90027
    2 Mattel Children's Hospital (UCLA) Los Angeles California United States 90095
    3 Children's Hospital and Research Center of Oakland Oakland California United States 94609
    4 Children's Hospital of Orange County Orange California United States 92868
    5 Children's Hospital Colorado - Denver Aurora Colorado United States 84005
    6 Yale - New Haven Children's Hospital New Haven Connecticut United States 06520
    7 Nemours/Alfred I. DuPont Hospital for Children Wilmington Delaware United States 19803
    8 Children's Healthcare of Atlanta (Emory) Atlanta Georgia United States 30322
    9 Ann & Robert H. Lurie Children's Hospital of Chicago Chicago Illinois United States 60611
    10 University of Chicago Medicine Comer Children's Hospital Chicago Illinois United States 60637
    11 Indiana University Riley Hospital for Children Indianapolis Indiana United States 46202
    12 University of Louisville Children's Hospital Louisville Kentucky United States 40202
    13 Children's Hospital of Boston Boston Massachusetts United States 02115
    14 C.S. Mott Children's Hospital - Michigan Ann Arbor Michigan United States 48109
    15 St. Louis Children's Hospital Saint Louis Missouri United States 63110
    16 Dartmouth Hitchcock Medical Center Manchester New Hampshire United States 03104
    17 Women and Children's Hospital of Buffalo Buffalo New York United States 14222
    18 Cohen Children's Medical Center of NY/ North Shore LIJ New Hyde Park New York United States 11743
    19 Maria Fareri Children's Hospital at Westchester Medical Center Valhalla New York United States 10595
    20 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229
    21 PennState Hershey Medical Center Hershey Pennsylvania United States 17033
    22 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    23 Medical City Children's Dallas Dallas Texas United States 75230
    24 Children's Medical Center Dallas Dallas Texas United States 75390
    25 Primary Children's Medical Center Salt Lake City Utah United States 84102

    Sponsors and Collaborators

    • University of California, San Francisco
    • National Heart, Lung, and Blood Institute (NHLBI)

    Investigators

    • Principal Investigator: Anil Sapru, MD,MAS, University of California, Los Angeles

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University of California, San Francisco
    ClinicalTrials.gov Identifier:
    NCT01892969
    Other Study ID Numbers:
    • A120253
    • 1R01HL114484-01A1
    First Posted:
    Jul 8, 2013
    Last Update Posted:
    Jul 31, 2020
    Last Verified:
    Jul 1, 2020
    Additional relevant MeSH terms:
    Respiratory Insufficiency

    Study Results

    No Results Posted as of Jul 31, 2020