Endothelium in Severe Sepsis

NCT00793442 | Completed DMC

• 2 other identifiers: 2008P0000891R01HL091757-01A1
• Study Type: observational
• Target: 910
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Sepsis; Severe Sepsis; Septic Shock

Keywords

sepsis; severe sepsis; septic shock; endothelium; microcirculation; biomarkers

Outcome Measures

Primary Outcomes (1)

• Mortality

  hospital mortality

Secondary Outcomes (1)

• Organ Dysfunction assessed by Sepsis-related Organ Failure Assessment (SOFA) Score

  first 72 hours

Study Arms (2)

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.

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.

Diagnostic Test: Blood Collection and Assays

Interventions

Blood Collection and Assays DIAGNOSTIC_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.

Novel Endothelial Marker Validation; Novel Endothelial Markers Derivation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Emergency department patients with severe sepsis

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (7)

Universtiy of Alabama

Birmingham, Alabama, 35249, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15261, United States

Location

University of Utah Health Sciences Center

Salt Lake City, Utah, 84132, United States

Location

Related Publications (2)

• 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.

  PMID: 28109962 RESULT

• Fabian-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.

  PMID: 30268146 DERIVED

MeSH Terms

Conditions

Sepsis; Shock, Septic

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Nathan I Shapiro, MD, MPH

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Emergency Medicine

Study Record Dates

• First Submitted: November 18, 2008
• First Posted: November 19, 2008
• Study Start: March 1, 2008
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: October 29, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)