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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

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.

Condition or disease Intervention/treatment
Sepsis Procedure: Septic patients Procedure: Healthy Control

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.

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Study Type : Observational
Actual Enrollment : 63 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Hypoxia Inducible Factor 1 Alpha as a Novel Biomarker in Septic Shock
Study Start Date : January 2013
Actual Primary Completion Date : June 2015
Actual Study Completion Date : June 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sepsis Shock

Group/Cohort Intervention/treatment
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.
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.

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.
Procedure: Healthy Control
The investigators will draw 10 mL, once, during baseline for a total of 10 mL among the healthy control group.




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.


Biospecimen Retention:   Samples With DNA
whole blood, serum


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Normal healthy controls recruited from the community. Subjects with sepsis admitted to the University of Florida Hospital.
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

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 ClinicalTrials.gov identifier (NCT number): NCT02163473


Locations
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United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
Sponsors and Collaborators
University of Florida
Investigators
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Principal Investigator: Wael Nasser, MD University of Florida
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Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT02163473    
Other Study ID Numbers: IRB201200142
First Posted: June 13, 2014    Key Record Dates
Last Update Posted: October 13, 2016
Last Verified: October 2016
Additional relevant MeSH terms:
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Hypoxia
Signs and Symptoms, Respiratory