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

Sepsis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02163473
• Other study ID #: IRB201200142
• Status: Completed
• Phase: N/A
• First received: June 5, 2014
• Last updated: October 12, 2016
• Start date: January 2013
• Est. completion date: June 2015

Study information

• Verified date: October 2016
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Sepsis
• Shock, Septic

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

Locations

Country	Name	City	State
United States	University of Florida	Gainesville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Florida

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hypoxia-inducible factor as a predictive biomarker of sepsis.	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.	Baseline,	No
Primary	Hypoxia-inducible factor as a predictive biomarker of sepsis	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.	24 hours	No
Secondary	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.	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.	28 days	No