SepsisNCT02163473
Hypoxia Inducible Factor 1 Alpha as a Novel Biomarker in Septic Shock
An observational study of Sepsis, run by University of Florida at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Sepsis
- What is being tested?
- Septic patients
- Type of treatment
- Surgery or procedure
- How many people
- 63 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2013to Jun 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Normal healthy controls recruited from the community. Subjects with sepsis admitted to the University of Florida Hospital.
Who may be able to join
- 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
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- 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
- Age and gender-matched to sepsis patients
- Negative pregnancy test in women of childbearing potential
- Never smoker (<1 pack year history)
Who cannot join
- 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
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- Transplant recipient
- Known HIV
- Use of ≥ 15 mg prednisone daily or equivalent
- Severe anemia: hematocrit ≤ 20
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Sepsis
- Being tested
- Septic patients, Healthy Control
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Septic patientsProcedure or surgery
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 ControlProcedure or surgery
The investigators will draw 10 mL, once, during baseline for a total of 10 mL among the healthy control group.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Procedure: Healthy Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline,
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.
Measured: 24 hours
Secondary outcomes (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.
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.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2014 (estimated)
- Study startJan 2013
- Primary completionJun 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Wael Nasser, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02163473
- Sponsor's protocol ID
- IRB201200142
- Status last verified
- Oct 2016
- First submitted
- 5 Jun 2014
- Last updated
- 13 Oct 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hypoxia Inducible Factor 1 Alpha as a Novel Biomarker in Septic Shock
- ClinicalTrials.gov ID
- NCT02163473
- Acronym / sponsor ID
- IRB201200142
- Conditions
- Sepsis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- Jan 2013
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 13 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Septic patients | – | Procedure: Septic patientsBlood 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. |
| Healthy Control | – | Procedure: Healthy ControlThe 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Normal healthy controls recruited from the community. Subjects with sepsis admitted to the University of Florida Hospital.
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Septic patientsThe 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 or surgery | Septic patients |
| Healthy ControlThe investigators will draw 10 mL, once, during baseline for a total of 10 mL among the healthy control group. | Procedure or surgery | Healthy Control |
Primary outcome
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.
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wael Nasser, MD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sepsis, run by University of Florida at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hypoxia-inducible factor as a predictive biomarker of sepsis. (time frame: Baseline,). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2016.