Sepsis | Endothelium in Severe Sepsis

Sepsis research study

What is the primary objective of this study?

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.

Who is eligible to participate?

Inclusion Criteria: - Enrolled as a participant in the ProCESS Trial ( 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) 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)

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?


Severe Sepsis

Septic Shock

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Diagnostic Test: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.

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

Novel Endothelial Markers DerivationOur 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 ValidationOur 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.

Study Status


Start Date: March 2008

Completed Date: May 2013

Phase: N/A

Type: Observational


Primary Outcome: Mortality

Secondary Outcome: Organ Dysfunction assessed by Sepsis-related Organ Failure Assessment (SOFA) Score

Study sponsors, principal investigator, and references

Principal Investigator: Nathan I Shapiro, MD, MPH

Lead Sponsor: Beth Israel Deaconess Medical Center

Collaborator: National Heart, Lung, and Blood Institute (NHLBI)

More information:

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.

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