SepsisNCT00793442
Endothelium in Severe Sepsis
An observational study of Sepsis and Severe Sepsis, run by Beth Israel Deaconess Medical Center at 7 sites in United States.
Trial summary
The overall hypotheses of this project is that severe sepsis is associated with endothelial dysfunction; that endothelial dysfunction, in turn, is predictive of subsequent organ failure and death; and that protocolized resuscitation attenuates endothelial cell (EC) dysfunction and improves patient survival. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, Severe Sepsis, Septic Shock
- What is being tested?
- Blood Collection and Assays
- How many people
- 910 participants
- Where
- 7 sitesUnited States
- Study dates
- Mar 2008to May 2013
- 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: Emergency department patients with severe sepsis
Who may be able to join
- Enrolled as a participant in the ProCESS Trial (clinicaltrial.gov identifier NCT00510835)
- At least 18 years of age
- Suspected infection
- Two or more systemic inflammatory response syndrome (SIRS) criteria
- Temperature </= 36˚ C or >/= 38˚C
- Heart rate >/= 90 beats per minute
Show all 9Show fewer
- Mechanical ventilation for acute respiratory process or respiratory rate >/= 20 breaths per minute or PaC02 < 32 mmHg
- WBC >/= 12,000/mm³ OR </= 4,000/mm³ OR > 10% bands
- Refractory hypotension (a systolic blood pressure < 90 mm Hg despite an IV fluid challenge of at least 20 ml/kg over a 30 minute period) or evidence of hypoperfusion (a blood lactate concentration >/= 4 mmol/L)
Who cannot join
- Known pregnancy
- Primary diagnosis of acute cerebral vascular event, acute coronary syndrome, -- acute pulmonary edema, status asthmaticus, major cardiac arrhythmia, active
- gastrointestinal hemorrhage, seizure, drug overdose, burn or trauma
- Requirement for immediate surgery
- ANC < 500/mm³
- CD4 < 50/mm³
Show all 14Show fewer
- Do-not-resuscitate status
- Advanced directives restricting implementation of the protocol
- Contraindication to central venous catheterization
- Contradiction to blood transfusion (e.g., Jehovah's Witness)
- Treating physician deems aggressive care unsuitable
- Participation in another interventional study
- Transferred from another in-hospital setting
- inability to tolerate microscan procedure (eg oxygen requirement via face mack that can not be discontinue for the procedure)
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Universtiy of Alabama
Birmingham, Alabama, 35249
Massachusetts General Hospital
Boston, Massachusetts, 02114
Brigham and Women's Hospital
Boston, Massachusetts, 02115
North Shore University Hospital
Manhasset, New York, 11030
Temple University Hospital
Philadelphia, Pennsylvania, 19140
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15261
University of Utah Health Sciences Center
Salt Lake City, Utah, 84132
About this study
Official title: Endothelial Cell Signaling and Microcirculatory Flow in Severe Sepsis
The overall hypotheses of this project is that severe sepsis is associated with endothelial dysfunction; that endothelial dysfunction, in turn, is predictive of subsequent organ failure and death; and that protocolized resuscitation attenuates endothelial cell (EC) dysfunction and improves patient survival.
Read the detailed description
The endothelial response is emerging as a critical element of sepsis pathophysiology. Preclinical data and small human studies suggest that endothelial cells are responsible for increased leukocyte adhesion, inflammation, activation of coagulation, and respond to increased levels of the endothelial cell mediator Vascular Endothelial Cell Growth Factor (VEGF). Furthermore, the endothelium plays an active role in microcirculatory homeostasis and the preservation of microvascular flow.
The researchers propose to study the endothelium by performing a comprehensive endothelial cell "read-out" through the measurement of circulating levels of endothelial cell biomarkers as well as direct visualization of microcirculatory flow with in-vivo videomicroscopy. Accordingly, the broad, long-term objective of this project is to study the role of the endothelium in sepsis in a large, heterogeneous group of patients. To accomplish this, the researchers will investigate two specific aims: 1) to study biomarkers of endothelial cell activation in sepsis; and, 2) to study microcirculatory flow in sepsis.
The overall hypotheses of this project is that severe sepsis is associated with endothelial dysfunction; that endothelial dysfunction, in turn, is predictive of subsequent organ failure and death; and that protocolized resuscitation attenuates endothelial cell (EC) dysfunction and improves patient survival. To test these hypotheses the researchers will utilize ancillary measurements (notably in-vivo assessment of microcirculatory flow), and additional samples and assays from the ProCESS clinical trial. ProCESS is a large, multicenter, randomized, controlled clinical trial testing the efficacy and mechanisms behind protocolized goal-directed resuscitation.
To conduct this line of investigation directed at the endothelium and microcirculation that was not addressed in the original trial, the researchers will select 8 ProCESS study sites for participation in this ancillary study. The researchers will directly visualize and quantify the presence of disturbances in sublingual microcirculatory flow utilizing the novel bedside technique of orthogonal polarization microscopy. Furthermore, the researchers will develop a multi-marker panel that assesses degree of endothelial cell dysfunction and subsequent mortality risk.
The researchers will also capitalize on the randomly assigned interventions in the ProCESS clinical trial to observe differences in endothelial response across the alternative resuscitation strategies. Improved understanding of these mechanisms may lead to strategies to predict outcome, to select patients for tailored (endothelium-directed) therapies, to follow treatment response, and to develop novel therapies for endothelial dysfunction in sepsis.
- Conditions
- Sepsis, Severe Sepsis, Septic Shock
- Being tested
- Blood Collection and Assays
- Keywords
- sepsis, severe sepsis, septic shock, endothelium, microcirculation, biomarkers
- Medical subject headings
- Sepsis, Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood Collection and AssaysDiagnostic test
The researchers will sample blood upon enrollment, at 6 and 24 hours after the baseline sampling. The researchers will measure 6 different endothelial related biomarkers compromising different components of endothelial permeability and hemostasis.
| Study group | Role | What they receive |
|---|---|---|
| Novel Endothelial Markers Derivation | Our study participants will come from the Protocolized Care for Early Severe Sepsis (ProCESS) trial will be eligible participants.
From the ProCESS subjects, the researchers will include those who were: 1) recruited by participating centers who participated in other components of this ancillary study or 2) who were sequentially enrolled from periods derived from the beginning, middle, and end of the ProCESS study. Receives: Diagnostic Test: Blood Collection and Assays | |
| Novel Endothelial Marker Validation | Our study participants will come from the Protocolized Care for Early Severe Sepsis (ProCESS) trial will be eligible participants; the researchers will recruit a sequential 300 patient validation set. Receives: Diagnostic Test: Blood Collection and Assays |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality
Measured: hospital mortality
Secondary outcomes (1)
Organ Dysfunction assessed by Sepsis-related Organ Failure Assessment (SOFA) Score
Measured: first 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2008 (estimated)
- Study startMar 2008
- Primary completionMay 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by Beth Israel Deaconess Medical CenterThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 910 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Nathan Shapiro, Beth Israel Deaconess Medical Center
- Investigators
- Nathan I Shapiro, MD, MPH, Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00793442
- Sponsor's protocol ID
- 2008P000089
- Other IDs
- 1R01HL091757-01A1
- Status last verified
- Oct 2024
- First submitted
- 18 Nov 2008
- Last updated
- 29 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hou PC, Filbin MR, Wang H, Ngo L, Huang DT, Aird WC, Yealy DM, Angus DC, Kellum JA, Shapiro NI; ProCESS Investigators( *). Endothelial Permeability and Hemostasis in Septic Shock: Results From the ProCESS Trial. Chest. 2017 Jul;152(1):22-31. doi: 10.1016/j.chest.2017.01.010. Epub 2017 Jan 19.
PubMed 28109962Fabian-Jessing BK, Massey MJ, Filbin MR, Hou PC, Wang HE, Kirkegaard H, Yealy DM, Aird WC, Kellum JA, Angus DC, Shapiro NI; ProCESS Investigators. In vivo quantification of rolling and adhered leukocytes in human sepsis. Crit Care. 2018 Sep 30;22(1):240. doi: 10.1186/s13054-018-2173-z.
PubMed 30268146
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endothelial Cell Signaling and Microcirculatory Flow in Severe Sepsis
- ClinicalTrials.gov ID
- NCT00793442
- Acronym / sponsor ID
- 2008P000089
- Conditions
- Sepsis, Severe Sepsis, Septic Shock
- Keywords
- sepsis, severe sepsis, septic shock, endothelium, microcirculation, biomarkers
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 910 participants (actual)
- Lead sponsor
- Beth Israel Deaconess Medical CenterUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Mar 2008 (actual)
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 19 Nov 2008 (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 overall hypotheses of this project is that severe sepsis is associated with endothelial dysfunction; that endothelial dysfunction, in turn, is predictive of subsequent organ failure and death; and that protocolized resuscitation attenuates endothelial cell (EC) dysfunction and improves patient survival.
Detailed description
The endothelial response is emerging as a critical element of sepsis pathophysiology. Preclinical data and small human studies suggest that endothelial cells are responsible for increased leukocyte adhesion, inflammation, activation of coagulation, and respond to increased levels of the endothelial cell mediator Vascular Endothelial Cell Growth Factor (VEGF). Furthermore, the endothelium plays an active role in microcirculatory homeostasis and the preservation of microvascular flow.
The researchers propose to study the endothelium by performing a comprehensive endothelial cell "read-out" through the measurement of circulating levels of endothelial cell biomarkers as well as direct visualization of microcirculatory flow with in-vivo videomicroscopy. Accordingly, the broad, long-term objective of this project is to study the role of the endothelium in sepsis in a large, heterogeneous group of patients. To accomplish this, the researchers will investigate two specific aims: 1) to study biomarkers of endothelial cell activation in sepsis; and, 2) to study microcirculatory flow in sepsis.
The overall hypotheses of this project is that severe sepsis is associated with endothelial dysfunction; that endothelial dysfunction, in turn, is predictive of subsequent organ failure and death; and that protocolized resuscitation attenuates endothelial cell (EC) dysfunction and improves patient survival. To test these hypotheses the researchers will utilize ancillary measurements (notably in-vivo assessment of microcirculatory flow), and additional samples and assays from the ProCESS clinical trial. ProCESS is a large, multicenter, randomized, controlled clinical trial testing the efficacy and mechanisms behind protocolized goal-directed resuscitation.
To conduct this line of investigation directed at the endothelium and microcirculation that was not addressed in the original trial, the researchers will select 8 ProCESS study sites for participation in this ancillary study. The researchers will directly visualize and quantify the presence of disturbances in sublingual microcirculatory flow utilizing the novel bedside technique of orthogonal polarization microscopy. Furthermore, the researchers will develop a multi-marker panel that assesses degree of endothelial cell dysfunction and subsequent mortality risk.
The researchers will also capitalize on the randomly assigned interventions in the ProCESS clinical trial to observe differences in endothelial response across the alternative resuscitation strategies. Improved understanding of these mechanisms may lead to strategies to predict outcome, to select patients for tailored (endothelium-directed) therapies, to follow treatment response, and to develop novel therapies for endothelial dysfunction in sepsis.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Novel Endothelial Markers Derivation | – | Diagnostic Test: Blood Collection and AssaysOur study participants will come from the Protocolized Care for Early Severe Sepsis (ProCESS) trial will be eligible participants. From the ProCESS subjects, the researchers will include those who were: 1) recruited by participating centers who participated in other components of this ancillary study or 2) who were sequentially enrolled from periods derived from the beginning, middle, and end of the ProCESS study. |
| Novel Endothelial Marker Validation | – | Diagnostic Test: Blood Collection and AssaysOur study participants will come from the Protocolized Care for Early Severe Sepsis (ProCESS) trial will be eligible participants; the researchers will recruit a sequential 300 patient validation set. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Emergency department patients with severe sepsis
Key inclusion criteria (9 listed)
- Enrolled as a participant in the ProCESS Trial (clinicaltrial.gov identifier NCT00510835)
- At least 18 years of age
- Suspected infection
- Two or more systemic inflammatory response syndrome (SIRS) criteria
- Refractory hypotension (a systolic blood pressure < 90 mm Hg despite an IV fluid challenge of at least 20 ml/kg over a 30 minute period) or evidence of hypoperfusion (a blood lactate concentration >/= 4 mmol/L)
Key exclusion criteria (14 listed)
- Known pregnancy
- Primary diagnosis of acute cerebral vascular event, acute coronary syndrome, -- acute pulmonary edema, status asthmaticus, major cardiac arrhythmia, active
- gastrointestinal hemorrhage, seizure, drug overdose, burn or trauma
- Requirement for immediate surgery
- ANC < 500/mm³
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 |
|---|---|---|
| Blood Collection and AssaysThe researchers will sample blood upon enrollment, at 6 and 24 hours after the baseline sampling. The researchers will measure 6 different endothelial related biomarkers compromising different components of endothelial permeability and hemostasis. | Diagnostic test | Novel Endothelial Marker Validation, Novel Endothelial Markers Derivation |
Primary outcome
Mortality
Time frame: hospital mortality
1 secondary outcome
Organ Dysfunction assessed by Sepsis-related Organ Failure Assessment (SOFA) Score
Time frame: first 72 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 29 Oct 2024.
- Results publication: PubMed 28109962Hou PC, Filbin MR, Wang H, Ngo L, Huang DT, Aird WC, Yealy DM, Angus DC, Kellum JA, Shapiro NI; ProCESS Investigators( *). Endothelial Permeability and Hemostasis in Septic Shock: Results From the ProCESS Trial. Chest. 2017 Jul;152(1):22-31. doi: 10.1016/j.chest.2017.01.010. Epub 2017 Jan 19.
- Derived from this study: PubMed 30268146Fabian-Jessing BK, Massey MJ, Filbin MR, Hou PC, Wang HE, Kirkegaard H, Yealy DM, Aird WC, Kellum JA, Angus DC, Shapiro NI; ProCESS Investigators. In vivo quantification of rolling and adhered leukocytes in human sepsis. Crit Care. 2018 Sep 30;22(1):240. doi: 10.1186/s13054-018-2173-z.
- Individual participant dataSharing planned: No
Related trials for Sepsis
RecruitingPhase 2
Combination Cefazolin With Ertapenem for Methicillin-susceptible Staphylococcus Aureus Bacteremia
Staphylococcus Aureus Bacteremia, Staphylococcus Aureus Septicemia
Not yet recruiting
Personalized Metabolic Nutrition Sepsis Study
Pediatric Sepsis
RecruitingObservational study
Immunothrombosis With Septic Shock Undergoing Renal Replacement Therapy With the OXIRIS Membrane
Sepsis
RecruitingObservational study
Middle East Study of Infections in Patients With Hematological Malignancies
Hematological Malignancy, Hematopoetic Stem Cell Transplantation
RecruitingPhase 3
A Trial of Adjunctive Fludrocortisone (50mcg, 100mcg or Placebo) in Critically Ill Patients With Septic Shock Receiving Hydrocortisone, Evaluating Survival and Functional Recovery and the Influence of Transcriptomic Response
Septic Shock
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.
Nathan I Shapiro, MD, MPH principal investigator
Beth Israel Deaconess Medical Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sepsis and Severe Sepsis, run by Beth Israel Deaconess Medical Center at 7 sites 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 9 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 29 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites 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?
Mortality (time frame: hospital mortality). 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 NCT00793442, which also lists 2 linked publications.
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 29 Oct 2024.