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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01892969
Recruitment Status : Completed
First Posted : July 8, 2013
Last Update Posted : July 31, 2020
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
University of California, San Francisco

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
Heart Failure Respiratory Failure

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.

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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 : October 2012
Actual Primary Completion Date : September 2016
Actual Study Completion Date : September 2016

Patients with Heart failure or Respiratory Failure with Hyperglycemia

Primary Outcome Measures :
  1. Biomarkers of Thrombosis and Inflammation (Interleukin 6 (IL6) and Interleukin 8 (IL8) , Plasminogen Activator Inhibitor -1 (PAI-1)) [ Time Frame: 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) [ Time Frame: 28 days ]
    Acute Lung Injury (ALI) measured as hypoxemia with bilateral infiltrates

Biospecimen Retention:   Samples With DNA
Blood Samples

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients Enrolled in the Half Pint Trial to study the efficacy of Tight Glycemic control using Insulin on reducing organ failure and mortality among children with Heart and Lung Failure with Hyperglycemia

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01892969

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Sponsors and Collaborators
University of California, San Francisco
National Heart, Lung, and Blood Institute (NHLBI)
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Principal Investigator: Anil Sapru, MD,MAS University of California, Los Angeles
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Responsible Party: University of California, San Francisco Identifier: NCT01892969    
Other Study ID Numbers: A120253
1R01HL114484-01A1 ( U.S. NIH Grant/Contract )
First Posted: July 8, 2013    Key Record Dates
Last Update Posted: July 31, 2020
Last Verified: July 2020
Additional relevant MeSH terms:
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Respiratory Insufficiency
Respiration Disorders
Respiratory Tract Diseases