Severe SepsisNCT02370186
The Role of Dysfunctional HDL in Severe Sepsis
An observational study of Severe Sepsis and Septic Shock, run by University of Florida at 1 site in United States.
Trial summary
Severe sepsis results in over 300,000 Emergency Department (ED) visits and 215,000 deaths annually in the US. Currently there are no effective drug therapies for sepsis. High density lipoprotein (HDL) has antioxidant, anti-inflammatory, and antithrombotic properties and is protective in sepsis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Severe Sepsis, Septic Shock, Sepsis
- How many people
- 110 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2015to 12 Mar 2017
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adults who present to one Emergency Department and who meet criteria for severe sepsis or septic shock.
Who may be able to join
- Patients 18 years and older with at least 2 of 4 SIRS criteria plus:
- lactate ≥ 2 mg/dL, AND
- SOFA Score ≥ 4* (see Appendix A), or
Who cannot join
- Patients <18 years of age
- Pregnant subjects
- No valid consent available
- Familial/genetic disorders of lipid metabolism
Trial locations and contacts
1 site in 1 country.
About this study
Severe sepsis results in over 300,000 Emergency Department (ED) visits and 215,000 deaths annually in the US. Currently there are no effective drug therapies for sepsis. High density lipoprotein (HDL) has antioxidant, anti-inflammatory, and antithrombotic properties and is protective in sepsis. Its functions in sepsis are primarily mediated by its main apolipoprotein, Apo-A1, that: 1) neutralize potent bacterial toxins, 2) protect blood vessel walls from damage, 3) prevent tissue damage through antioxidant properties, and 4) mediate thymocyte apoptosis (critical for survival) and endogenous corticosteroid release. However, recent literature presents inconsistent data on HDL functionality and shows that HDL becomes non-functional during acute inflammatory states called dysfunctional HDL (Dys-HDL). Several causes for Dys-HDL have been hypothesized including the presence of Apo A1 polymorphisms, which may worsen the pathologic inflammatory response in sepsis and have been demonstrated in early sepsis, making Dys-HDL an unstudied potential early marker. This project aims to: 1) determine the presence of Dys-HDL in adult patients with early severe sepsis who present to the ED (Dys-HDL will be tested using a novel cell free assay and HDL Inflammatory Index will be measured), and 2) examine the relationship between Dys-HDL and cumulative organ dysfunction via Sequential Organ Failure Assessment (SOFA) score. Results of this study could establish Dys-HDL as an early disease marker for sepsis which is influential in the development of sepsis-induced organ dysfunction.
Read the detailed description
Sepsis is a systemic inflammatory response to infection, which leads to acute organ dysfunction and shock. Current therapies are aimed at normalizing hemodynamic parameters during early sepsis resuscitation to reduce mortality. The investigators hypothesize that future strategies should be personalized, and should target the mediators of the septic response on an individual patient basis. One of these mediators is HDL which works by facilitating clearance of bacterial toxins, maintaining the integrity of the endothelium, and preventing inflammation, a function performed by Apo-A1. The association of HDL with cardiovascular health has been well-studied in the Caucasian and Asian populations, where research has demonstrated that HDL can become pro-inflammatory and thus may not perform its functions of being anti-inflammatory, anti-thrombotic and anti-oxidant. Such HDL is called Dys-HDL. Dys-HDL or pro-inflammatory HDL may play a pivotal role in sepsis, an area that has not been fully studied. The mechanism by which HDL becomes dysfunctional is one of debate, but the main hypothesis is through polymorphisms of Apo-A1, possibly via the myeloperoxidase enzyme, and each polymorphism produces different HDL levels and activity. These alterations can lead to increased susceptibility to septic death due to inability to neutralize lipopolysaccharide, loss of thymocyte apoptosis (critical for protection against sepsis) and endogenous corticosteroid release, and loss of the ability to preserve HDLs antioxidant properties. Dys-HDL has also been demonstrated in early sepsis and may serve as a potential early disease marker. For these reasons, the investigators believe that Dys-HDL may play a pivotal role in the sepsis cascade which leads to organ dysfunction and death. Aim 1. Determine the presence of Dys-HDL in adult patients with early severe sepsis who present to the ED. Aim 2. Examine the relationship between Dys-HDL and cumulative organ dysfunction as measured by the sequential organ failure assessment (SOFA) score, a validated measure of organ dysfunction in severe sepsis.
- Conditions
- Severe Sepsis, Septic Shock, Sepsis
- Medical subject headings
- Sepsis, Shock, Septic
What is being measured
The primary outcome is the main question the study is designed to answer.
Dys-HDL in adult patients with early severe sepsis
Measure Dys-HDL in adult patients with early severe sepsis who present to the ED.
Measured: 48 hours
Secondary outcomes (1)
Relationship between Dys-HDL and Cumulative Organ Dysfunction
Examine the relationship between Dys-HDL and cumulative organ dysfunction as measured by the sequential organ failure assessment (SOFA) score.
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2015 (estimated)
- Study startFeb 2015
- Primary completion12 Mar 2017
- Study completion12 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Severe 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
- Other
- Time perspective
- Prospective
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- University of Mississippi Medical Center
- Responsible party
- Sponsor
- Investigators
- Faheem W Guirgis, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02370186
- Sponsor's protocol ID
- UFJ 2014-193
- Other IDs
- IRB201702454
- Status last verified
- Jan 2021
- First submitted
- 17 Feb 2015
- Last updated
- 27 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Guirgis FW, Dodani S, Leeuwenburgh C, Moldawer L, Bowman J, Kalynych C, Grijalva V, Reddy ST, Jones AE, Moore FA. HDL inflammatory index correlates with and predicts severity of organ failure in patients with sepsis and septic shock. PLoS One. 2018 Sep 14;13(9):e0203813. doi: 10.1371/journal.pone.0203813. eCollection 2018.
PubMed 30216360
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Dysfunctional HDL in Severe Sepsis
- ClinicalTrials.gov ID
- NCT02370186
- Acronym / sponsor ID
- UFJ 2014-193
- Conditions
- Severe Sepsis, Septic Shock, Sepsis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- University of Mississippi Medical Center
- Study start
- Feb 2015
- Primary completion
- 12 Mar 2017 (actual)
- Study completion
- 12 Mar 2017 (actual)
- First posted
- 24 Feb 2015 (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.
Severe sepsis results in over 300,000 Emergency Department (ED) visits and 215,000 deaths annually in the US. Currently there are no effective drug therapies for sepsis. High density lipoprotein (HDL) has antioxidant, anti-inflammatory, and antithrombotic properties and is protective in sepsis. Its functions in sepsis are primarily mediated by its main apolipoprotein, Apo-A1, that: 1) neutralize potent bacterial toxins, 2) protect blood vessel walls from damage, 3) prevent tissue damage through antioxidant properties, and 4) mediate thymocyte apoptosis (critical for survival) and endogenous corticosteroid release. However, recent literature presents inconsistent data on HDL functionality and shows that HDL becomes non-functional during acute inflammatory states called dysfunctional HDL (Dys-HDL). Several causes for Dys-HDL have been hypothesized including the presence of Apo A1 polymorphisms, which may worsen the pathologic inflammatory response in sepsis and have been demonstrated in early sepsis, making Dys-HDL an unstudied potential early marker. This project aims to: 1) determine the presence of Dys-HDL in adult patients with early severe sepsis who present to the ED (Dys-HDL will be tested using a novel cell free assay and HDL Inflammatory Index will be measured), and 2) examine the relationship between Dys-HDL and cumulative organ dysfunction via Sequential Organ Failure Assessment (SOFA) score. Results of this study could establish Dys-HDL as an early disease marker for sepsis which is influential in the development of sepsis-induced organ dysfunction.
Detailed description
Sepsis is a systemic inflammatory response to infection, which leads to acute organ dysfunction and shock. Current therapies are aimed at normalizing hemodynamic parameters during early sepsis resuscitation to reduce mortality. The investigators hypothesize that future strategies should be personalized, and should target the mediators of the septic response on an individual patient basis. One of these mediators is HDL which works by facilitating clearance of bacterial toxins, maintaining the integrity of the endothelium, and preventing inflammation, a function performed by Apo-A1. The association of HDL with cardiovascular health has been well-studied in the Caucasian and Asian populations, where research has demonstrated that HDL can become pro-inflammatory and thus may not perform its functions of being anti-inflammatory, anti-thrombotic and anti-oxidant. Such HDL is called Dys-HDL. Dys-HDL or pro-inflammatory HDL may play a pivotal role in sepsis, an area that has not been fully studied. The mechanism by which HDL becomes dysfunctional is one of debate, but the main hypothesis is through polymorphisms of Apo-A1, possibly via the myeloperoxidase enzyme, and each polymorphism produces different HDL levels and activity. These alterations can lead to increased susceptibility to septic death due to inability to neutralize lipopolysaccharide, loss of thymocyte apoptosis (critical for protection against sepsis) and endogenous corticosteroid release, and loss of the ability to preserve HDLs antioxidant properties. Dys-HDL has also been demonstrated in early sepsis and may serve as a potential early disease marker. For these reasons, the investigators believe that Dys-HDL may play a pivotal role in the sepsis cascade which leads to organ dysfunction and death. Aim 1. Determine the presence of Dys-HDL in adult patients with early severe sepsis who present to the ED. Aim 2. Examine the relationship between Dys-HDL and cumulative organ dysfunction as measured by the sequential organ failure assessment (SOFA) score, a validated measure of organ dysfunction in severe sepsis.
Study design
- Observational model
- Other
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adults who present to one Emergency Department and who meet criteria for severe sepsis or septic shock.
Key inclusion criteria (3 listed)
- Patients 18 years and older with at least 2 of 4 SIRS criteria plus:
Key exclusion criteria (4 listed)
- Patients <18 years of age
- Pregnant subjects
- No valid consent available
- Familial/genetic disorders of lipid metabolism
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Dys-HDL in adult patients with early severe sepsis
Time frame: 48 hours
Measure Dys-HDL in adult patients with early severe sepsis who present to the ED.
1 secondary outcome
Relationship between Dys-HDL and Cumulative Organ Dysfunction
Time frame: 48 hours
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 27 Jan 2021.
- Derived from this study: PubMed 30216360Guirgis FW, Dodani S, Leeuwenburgh C, Moldawer L, Bowman J, Kalynych C, Grijalva V, Reddy ST, Jones AE, Moore FA. HDL inflammatory index correlates with and predicts severity of organ failure in patients with sepsis and septic shock. PLoS One. 2018 Sep 14;13(9):e0203813. doi: 10.1371/journal.pone.0203813. eCollection 2018.
- Individual participant dataSharing planned: No
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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.
Faheem W Guirgis, 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 Severe Sepsis and Septic Shock, 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 3 inclusion and 4 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 27 Jan 2021. 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?
Dys-HDL in adult patients with early severe sepsis (time frame: 48 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02370186, which also lists 1 linked publication.
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 27 Jan 2021.