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

Heart Failure Clinical Trial

— CAF-PINT  

Official title:

Coagulation and Fibrinolysis in a Pediatric Insulin Titration Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01892969
• Other study ID #: A120253
• Secondary ID: 1R01HL114484-01A
• Status: Completed
• Start date: October 2012
• Est. completion date: September 2016

Study information

• Verified date: July 2020
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 304
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Respiratory Failure
• Respiratory Insufficiency

Locations

Country	Name	City	State
United States	C.S. Mott Children's Hospital - Michigan	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta (Emory)	Atlanta	Georgia
United States	Children's Hospital Colorado - Denver	Aurora	Colorado
United States	Children's Hospital of Boston	Boston	Massachusetts
United States	Women and Children's Hospital of Buffalo	Buffalo	New York
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	University of Chicago Medicine Comer Children's Hospital	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Children's Medical Center Dallas	Dallas	Texas
United States	Medical City Children's Dallas	Dallas	Texas
United States	PennState Hershey Medical Center	Hershey	Pennsylvania
United States	Indiana University Riley Hospital for Children	Indianapolis	Indiana
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	Mattel Children's Hospital (UCLA)	Los Angeles	California
United States	University of Louisville Children's Hospital	Louisville	Kentucky
United States	Dartmouth Hitchcock Medical Center	Manchester	New Hampshire
United States	Yale - New Haven Children's Hospital	New Haven	Connecticut
United States	Cohen Children's Medical Center of NY/ North Shore LIJ	New Hyde Park	New York
United States	Children's Hospital and Research Center of Oakland	Oakland	California
United States	Children's Hospital of Orange County	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	St. Louis Children's Hospital	Saint Louis	Missouri
United States	Primary Children's Medical Center	Salt Lake City	Utah
United States	Maria Fareri Children's Hospital at Westchester Medical Center	Valhalla	New York
United States	Nemours/Alfred I. DuPont Hospital for Children	Wilmington	Delaware

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biomarkers of Thrombosis and Inflammation (Interleukin 6 (IL6) and Interleukin 8 (IL8) , Plasminogen Activator Inhibitor -1 (PAI-1))	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.	4 days
Secondary	Number of participants with Development of Acute Lung Injury (ALI)	Acute Lung Injury (ALI) measured as hypoxemia with bilateral infiltrates	28 days