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Hypoxia Inducible Factor 1 Alpha as a Novel Biomarker in Septic Shock

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ClinicalTrials.gov Identifier: NCT02163473
Recruitment Status : Completed
First Posted : June 13, 2014
Last Update Posted : October 13, 2016
Sponsor:
Information provided by (Responsible Party):
University of Florida

Tracking Information
First Submitted Date June 5, 2014
First Posted Date June 13, 2014
Last Update Posted Date October 13, 2016
Study Start Date January 2013
Actual Primary Completion Date June 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: October 12, 2016)
  • Hypoxia-inducible factor as a predictive biomarker of sepsis. [ Time Frame: Baseline, ]
    Hypoxia-inducible factor will be measured at initial diagnosis (baseline) and 24 hours later in subjects with clinical presentation of sepsis and correlated with lactic acidosis.
  • Hypoxia-inducible factor as a predictive biomarker of sepsis [ Time Frame: 24 hours ]
    Hypoxia-inducible factor will be measured at initial diagnosis (baseline) and 24 hours later in subjects with clinical presentation of sepsis and correlated with lactic acidosis.
Original Primary Outcome Measures
 (submitted: June 11, 2014)
Hypoxia-inducible factor as a predictive biomarker of sepsis. [ Time Frame: Baseline, 24 hours ]
Hypoxia-inducible factor will be measured at initial diagnosis (baseline) and 24 hours later in subjects with clinical presentation of sepsis and correlated with lactic acidosis.
Change History
Current Secondary Outcome Measures
 (submitted: October 12, 2016)
Evaluate the role of HIF complex as biomarker and its correlation with "Survive the Sepsis Campaign 2012" gold standard septic shock severity and morbidity/mortality predictors. [ Time Frame: 28 days ]
At discharge a detailed chart analysis will be performed for the first 24 hrs, survival at 28 day; correlations of clinical course-derived data and serum cytokine content with the HIF content/expression and function will be analyzed by Spearman's rank correlation test.
Original Secondary Outcome Measures
 (submitted: June 11, 2014)
Hypoxia-inducible factor as a biomarker of morbidity and mortality in sepsis. [ Time Frame: 28 days ]
In subjects with sepsis, 28-day survival and hypoxia-inducible factor levels correlated with mortality to determine utility as a biomarker for mortality risk in sepsis.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Hypoxia Inducible Factor 1 Alpha as a Novel Biomarker in Septic Shock
Official Title Hypoxia Inducible Factor 1 Alpha as a Novel Biomarker in Septic Shock
Brief Summary The purpose of this research study is to determine if a chemical marker in the blood, hypoxia-inducible factor (HIF-1 alpha), can be used to predict subject's hospital outcomes when the subject is diagnosed with sepsis. Sepsis is defined as either the presence of pathogenic organisms or their toxins in the blood and tissues. Sepsis is one of the most significant challenges in critical care medicine. The investigators propose that hypoxia-induced expression of HIF-1 alpha will correlate with the clinical features of Sepsis and in the future, HIF-1 alpha may be used as a biomarker in Sepsis.
Detailed Description

Sepsis is one of the most significant challenges in critical care. Septic shock (SS) is the most severe form of sepsis and is associated with higher mortality, significant financial expenses and longer lengths of stay. Pathophysiological mechanisms of SS include 3 key components: 1) bacterial overgrowth, 2) spill of bacterial product into the blood causing hemodynamic insufficiency, and 3) both lead to tissue hypoxia (TH). To date the biomarkers of sepsis/SS are limited to hemodynamic parameters. However, aggressive fluid resuscitation does not fully prevent development of tissue hypoxia (TH). To date the investigators are limited in appreciating TH by measurement of lactic acid (LA), which is neither an early nor an accurate marker. Unfortunately, LA has limited predictive value in SS due to its complex metabolism. Thus, there is an acute need for biomarkers that would aid diagnosis and prognosis of sepsis/septic shock.

Cellular responses/adaptations to hypoxia rely on the transcription hypoxia-inducible factor HIF, a heterodimeric protein composed of a constitutively expressed subunit and an inducible (types 1, 2, and 3) subunit. More recently HIF was identified in diverse tissues including blood; it has been also shown that HIF expression in blood cells is representative of systemic tissues in hypoxic conditions.

Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
whole blood, serum
Sampling Method Non-Probability Sample
Study Population Normal healthy controls recruited from the community. Subjects with sepsis admitted to the University of Florida Hospital.
Condition Sepsis
Intervention
  • Procedure: Septic patients
    The investigators will draw two sets of blood samples. One at baseline, 10 mL, and another, 24 hours later, 10 mL, for a total of 20 mL.
  • Procedure: Healthy Control
    The investigators will draw 10 mL, once, during baseline for a total of 10 mL among the healthy control group.
Study Groups/Cohorts
  • Septic patients
    Blood Draw Biological samples: The investigators will collect blood and compare the expression of HIF complex in 3 distinct ways: between patients and controls, within the same patient in a time-dependent fashion, and between different patients.
    Intervention: Procedure: Septic patients
  • Healthy Control
    The investigators will collect blood and compare the expression of HIF complex in 3 distinct ways: between patients and controls, within the same patient in a time-dependent fashion, and between different patients.
    Intervention: Procedure: Healthy Control
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: September 17, 2015)
63
Original Estimated Enrollment
 (submitted: June 11, 2014)
130
Actual Study Completion Date June 2015
Actual Primary Completion Date June 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria: Septic patients

  • Age 18 ≤ 80 years
  • Negative pregnancy test for women of childbearing potential
  • Meets two or more of Systemic Inflammatory Response System (SIRS) criteria (tachypnea, tachycardia, hypo/hyperthermia, leukopenia/leukocytosis)
  • Evidence of tissue hypo-perfusion, or organ dysfunction by any of the following
  • Sepsis induced hypotension with systolic blood pressure <90
  • Lactate above 1.5 mmol/Liter
  • Urine output below 0.5 mL/kg/hr for more than 2 hours despite adequate fluid resuscitation
  • Tissue hypoxia
  • Bilirubin > 2 mg/dl in absence of liver cirrhosis
  • Creatinine (CR)> 2.0 mg/dL, Acute Kidney Injury as evident by CR increase by 0.5 mg/dL from baseline
  • Platelet count < 100,000
  • Coagulopathy with international normalized ratio (INR) >1.5

Inclusion: Healthy Controls

  • Age and gender-matched to sepsis patients
  • Negative pregnancy test in women of childbearing potential
  • Never smoker (<1 pack year history)

Exclusion Criteria: Septic patients

  • History of Malignancy, including carcinoma during the preceding 5 years.
  • Recent surgery, within 48 hours, or anticipated surgery within 24 hours
  • Contraindication for neck/chest central venous line
  • History of cardiopulmonary resuscitation (CPR) prior to inclusion
  • Transfer from another institution
  • History of cirrhosis
  • Transplant recipient
  • Known HIV
  • Use of ≥ 15 mg prednisone daily or equivalent
  • Severe anemia: hematocrit ≤ 20

Exclusion: Healthy Controls

  • History of Malignancy, including carcinoma during the preceding 5 years.
  • Taking any prescription medications, other than any type of prescribed hormonal birth control.
  • Current smoking history and/or > 1 pack year history
  • Current use (within the last week) anti-inflammatory medications, such as aspirin, ibuprofen, naproxen and/or prednisone
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02163473
Other Study ID Numbers IRB201200142
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party University of Florida
Study Sponsor University of Florida
Collaborators Not Provided
Investigators
Principal Investigator: Wael Nasser, MD University of Florida
PRS Account University of Florida
Verification Date October 2016