Clinical trial NCT01892969: Coagulation and Fibrinolysis in Pediatric Insulin Titration Trial (CAF-PINT)
Official title: Coagulation and Fibrinolysis in a Pediatric Insulin Titration Trial
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Heart Failure
Respiratory Failure
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2013-07-08
Enrollment: 304
Sex: ALL
Minimum age (years): 14
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Biomarkers of Thrombosis and Inflammation (Interleukin 6 (IL6) and Interleukin 8 (IL8) , Plasminogen Activator Inhibitor -1 (PAI-1))
timeFrame: 4 days
Secondary outcomes:
measure: Number of participants with Development of Acute Lung Injury (ALI)
timeFrame: 28 days
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Los Angeles
country: United States
facility: Mattel Children's Hospital (UCLA)
state: California
city: Oakland
country: United States
facility: Children's Hospital and Research Center of Oakland
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado - Denver
state: Colorado
city: New Haven
country: United States
facility: Yale - New Haven Children's Hospital
state: Connecticut
city: Wilmington
country: United States
facility: Nemours/Alfred I. DuPont Hospital for Children
state: Delaware
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta (Emory)
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medicine Comer Children's Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Riley Hospital for Children
state: Indiana
city: Louisville
country: United States
facility: University of Louisville Children's Hospital
state: Kentucky
city: Boston
country: United States
facility: Children's Hospital of Boston
state: Massachusetts
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital - Michigan
state: Michigan
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: Manchester
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Buffalo
country: United States
facility: Women and Children's Hospital of Buffalo
state: New York
city: New Hyde Park
country: United States
facility: Cohen Children's Medical Center of NY/ North Shore LIJ
state: New York
city: Valhalla
country: United States
facility: Maria Fareri Children's Hospital at Westchester Medical Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Hershey
country: United States
facility: PennState Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Dallas
country: United States
facility: Medical City Children's Dallas
state: Texas
city: Dallas
country: United States
facility: Children's Medical Center Dallas
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Medical Center
state: Utah
Study officials:
affiliation: University of California, Los Angeles
name: Anil Sapru, MD,MAS
role: PRINCIPAL_INVESTIGATOR
References: