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Sponsors and Collaborators: |
Beth Israel Deaconess Medical Center National Heart, Lung, and Blood Institute (NHLBI) |
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Information provided by: | Beth Israel Deaconess Medical Center |
ClinicalTrials.gov Identifier: | NCT00793442 |
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 early effective protocol-directed resuscitation attenuates endothelial dysfunction leading to improved survival.
Condition |
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Sepsis Severe Sepsis Septic Shock |
Study Type: | Observational |
Study Design: | Cohort, Prospective |
Official Title: | Endothelial Cell Signaling and Microcirculatory Flow in Severe Sepsis |
Estimated Enrollment: | 600 |
Study Start Date: | June 2008 |
Estimated Study Completion Date: | January 2010 |
Estimated Primary Completion Date: | January 2010 (Final data collection date for primary outcome measure) |
Groups/Cohorts |
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Severe Sepsis and Septic Shock
Adult patients with severe sepsis who are enrolled in the Protocolized Care for Early Severe Sepsis (ProCESS) trial will be eligible participants.
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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. We 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, we 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 early effective protocol-directed resuscitation attenuates endothelial dysfunction leading to improved survival. To test this hypothesis, we will utilize patients, 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, we will select 8 ProCESS study sites for participation in this ancillary study. We will directly visualize and quantify the presence of disturbances in sublingual microcirculatory flow utilizing the novel bedside technique of orthogonal polarization microscopy. Furthermore, we will develop a multi-marker panel that assesses degree of endothelial cell dysfunction and subsequent mortality risk. We 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.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Sampling Method: | Non-Probability Sample |
Emergency department patients with severe sepsis
Inclusion Criteria:
Exclusion Criteria:
United States, Alabama | |
Universtiy of Alabama | |
Birmingham, Alabama, United States, 35249 | |
United States, Massachusetts | |
Massachusetts General Hospital | |
Boston, Massachusetts, United States, 02114 | |
Brigham and Women's Hospital | |
Boston, Massachusetts, United States, 02115 | |
United States, New York | |
North Shore University Hospital | |
Manhasset, New York, United States, 11030 | |
United States, Pennsylvania | |
Temple University Hospital | |
Philadelphia, Pennsylvania, United States, 19140 | |
University of Pittsburgh Medical Center | |
Pittsburgh, Pennsylvania, United States, 15261 | |
United States, Utah | |
University of Utah Health Sciences Center | |
Salt Lake City, Utah, United States, 84132 |
Principal Investigator: | Nathan I Shapiro, MD, MPH | Beth Israel Deaconess Medical Center |
Responsible Party: | Beth Israel Daconess Medical Center ( Nathan Shapiro, MD, MPH ) |
Study ID Numbers: | 1R01HL091757-01A1, 1R01HL091757-01A1 |
Study First Received: | November 18, 2008 |
Last Updated: | November 18, 2008 |
ClinicalTrials.gov Identifier: | NCT00793442 |
Health Authority: | United States: Institutional Review Board |
sepsis severe sepsis septic shock |
endothelium microcirculation biomarkers |
Systemic Inflammatory Response Syndrome Sepsis Shock Shock, Septic Inflammation |
Pathologic Processes Infection |