Endothelium in Severe Sepsis

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2010 by Beth Israel Deaconess Medical Center.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Information provided by:
Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT00793442
First received: November 18, 2008
Last updated: February 3, 2010
Last verified: February 2010
  Purpose

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
Sepsis
Severe Sepsis
Septic Shock

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Endothelial Cell Signaling and Microcirculatory Flow in Severe Sepsis

Resource links provided by NLM:


Further study details as provided by Beth Israel Deaconess Medical Center:

Primary Outcome Measures:
  • Mortality [ Time Frame: hospital mortality ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Organ Dysfunction assessed by Sepsis-related Organ Failure Assessment (SOFA) Score [ Time Frame: first 72 hours ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 600
Study Start Date: June 2008
Estimated Study Completion Date: January 2012
Estimated Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
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.

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. 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Emergency department patients with severe sepsis

Criteria

Inclusion Criteria:

  • Enrolled as a participant in the ProCESS Trial
  • 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
  • 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)

Exclusion Criteria:

  • 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
  • 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00793442

Contacts
Contact: Nathan I Shapiro, MD, MPH 617-754-2343 Nshapiro@bidmc.harvard.edu

Locations
United States, Alabama
Universtiy of Alabama Recruiting
Birmingham, Alabama, United States, 35249
Contact: Jason R Begue, MD    205-975-7387    jbegue@uabmc.edu   
Principal Investigator: Jason R Begue, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Michael Filbin, MA    617-724-0348    mfilbin@partners.org   
Principal Investigator: Michael Filbin, MD         
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Peter Hou, MD    617-732-5640    phou@partners.org   
Principal Investigator: Peter Hou, MD         
United States, New York
North Shore University Hospital Not yet recruiting
Manhasset, New York, United States, 11030
Contact: Todd Slessinger, MD    516-562-2426    tslessinger@yahoo.com   
Principal Investigator: todd Slessinger, MD         
United States, Pennsylvania
Temple University Hospital Recruiting
Philadelphia, Pennsylvania, United States, 19140
Contact: Jacob Ufberg, MD    215-707-7550    ufbergjw@tuhs.temple.edu   
Principal Investigator: Jacob W Ufberg, MD         
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15261
Contact: Brian Suffoletto, MD    412-647-5300    Suffbp@upmc.edu   
Principal Investigator: Brian Suffoletto, MD         
United States, Utah
University of Utah Health Sciences Center Not yet recruiting
Salt Lake City, Utah, United States, 84132
Contact: Edward Kimball, MD    801-581-2088    edward.kimball@hsc.utah.edu   
Principal Investigator: Edward Kimball, MD         
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Investigators
Principal Investigator: Nathan I Shapiro, MD, MPH Beth Israel Deaconess Medical Center
  More Information

No publications provided

Responsible Party: Nathan Shapiro, MD, MPH, Beth Israel Daconess Medical Center
ClinicalTrials.gov Identifier: NCT00793442     History of Changes
Other Study ID Numbers: 1R01HL091757-01A1, 1R01HL091757-01A1
Study First Received: November 18, 2008
Last Updated: February 3, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Beth Israel Deaconess Medical Center:
sepsis
severe sepsis
septic shock
endothelium
microcirculation
biomarkers

Additional relevant MeSH terms:
Sepsis
Toxemia
Shock
Shock, Septic
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes

ClinicalTrials.gov processed this record on August 25, 2014