Protocolized Care for Early Septic Shock (ProCESS)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00510835
First received: July 18, 2007
Last updated: June 6, 2013
Last verified: June 2013
  Purpose

The ProCESS study is large, 5-year, multicenter study of alternative resuscitation strategies for septic shock. The study hypothesizes that there are "golden hours" in the initial management of septic shock where prompt, rigorous, standardized care can improve clinical outcomes.


Condition Intervention
Sepsis
Severe Sepsis
Septic Shock
Procedure: Early Goal Directed Therapy (EGDT)
Procedure: Protocolized Standard Care (PSC)
Procedure: Usual Care (UC)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Protocolized Care for Early Septic Shock

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Hospital mortality [ Time Frame: prior to discharge or 60 days, whichever comes first ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in markers of inflammation, oxidative stress, cellular hypoxia and coagulation/thrombosis. [ Time Frame: study hour 0, 6, 24 & 72 ] [ Designated as safety issue: No ]
  • Resource use and costs of alternative resuscitation strategies [ Time Frame: at discharge or 60 days, whichever comes first ] [ Designated as safety issue: No ]

Enrollment: 1351
Study Start Date: March 2008
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Early Goal Directed Therapy (EGDT) - The study team will insert a central venous catheter (CVC) for continuous monitoring of the subjects' central venous pressure (CVP) and central venous oxygen saturation (Scv02). The study team will use this information to give fluid, blood, and heart medications in a structured fashion. The CVC is FDA approved and routinely used in hospitals.
Procedure: Early Goal Directed Therapy (EGDT)
Subjects will have a CVC inserted for continuous monitoring of their CVP and Scv02. Early structured treatment will be provided based on subjects' CVP, mean arterial pressure (MAP) and Scv02 measurements.
Experimental: 2
Protocolized Standard Care (PSC)- The study team will monitor the subjects' blood pressure and blood oxygen level with routine equipment. The study team will use this information to give fluid and heart medications in a structured fashion. CVCs will only be used when standard IVs are unable to give the proper amount of fluids and medicines. Blood transfusions will be given according to currently recommended guidelines.
Procedure: Protocolized Standard Care (PSC)
Routine equipment will be used to monitor subjects' blood pressure and oxygen levels. Early structured treatment is based on the subjects' systolic blood pressure and the study doctors' judgment of fluid status and perfusion status.
Active Comparator: 3
Usual Care - The attending physicians will treat the subjects according to their standard treatment plan and without any influence from the study team. A member of the study team will simply observe and record what happens.
Procedure: Usual Care (UC)
Attending physicians will provide routine care to subjects. Study measurements and treatments will be based on the physicians'/sites' standard practices.

Detailed Description:

Septic shock is a condition of acute organ dysfunction due to severe infection, with a mortality of up to 50%. Current efforts to improve care are limited by little practical evidence regarding the interventions in and timing of sepsis therapies. ProCESS is a prospective, randomized, three-arm parallel-group trial of alternative resuscitation strategies for early septic shock. The study objective is to improve the management of septic shock by exploring the clinical, biological, and economic aspects of alternative resuscitation strategies. This will be done by comparing two alternative resuscitation strategies to usual care in subjects with septic shock.

Comparisons:

  1. Early Goal Directed Therapy (EGDT) - The subjects' blood pressure and blood oxygen levels will be monitored via the insertion of a central venous catheter (CVC). The study team will use this information to give fluid, blood and heart medications in a structured fashion. The central venous catheter to be used in this plan is FDA approved and routinely used in hospitals.
  2. Protocolized Standard Care (PSC) - The subjects' blood pressure and blood oxygen levels will be monitored with standard equipment (without the CVC). The study team will use this information to prescribe fluid and heart medications in a structured fashion. CVCs will only be used when standard IVs cannot give the proper amount of fluids and medicines. Blood transfusions will be given according to currently recommended guidelines.
  3. Usual Care (UC) - Subjects will be treated according to their attending physician's standard treatment plan and without any influence from the study team.

The primary hypotheses to be tested sequentially are that: protocolized resuscitation (EGDT and PSC) results in lower hospital mortality than usual care and Early Goal Directed Therapy results in lower hospital mortality than Protocolized Standard Care. These hypotheses will be tested on all enrolled subjects.

The study is powered to find an absolute mortality reduction (ARR) of ~6-7%. Based on the control arm mortality rate, we originally estimated a sample size of 1950. During the trial, the ProCESS Coordinating Center monitored the overall mortality rate, and appreciated that it was markedly lower than originally projected. Therefore, following a series of new calculations, in February 2013, the trial was re-sized to 1350 patients (450 patients per arm). The new size preserves the same power to find the same ARR. The resizing was fully blinded and approved by the NIH.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • 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 1,000 mLs 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
  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: NCT00510835

  Hide Study Locations
Locations
United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35249
United States, Arizona
Maricopa Medical Center
Phoenix, Arizona, United States, 85008
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
LA County & USC Medical Center
Los Angeles, California, United States, 90033
Stanford University School of Medicine
Palo Alto, California, United States, 94025
UC Davis Medical Center
Sacramento, California, United States, 95817
United States, Connecticut
Norwalk Hospital
Norwalk, Connecticut, United States, 06856
United States, District of Columbia
George Washington University Medical Center
Washington, District of Columbia, United States, 20037
Washington Hospital Center
Washington, District of Columbia, United States, 20010
United States, Florida
Tampa General Hospital
Tampa, Florida, United States, 33601
United States, Illinois
Advocate Christ Medical Center
Oak Lawn, Illinois, United States, 60453
United States, Indiana
Methodist Research Institute
Indianapolis, Indiana, United States, 46202
United States, Louisiana
Louisiana State University Health Sciences Center/Shreveport
Shreveport, Louisiana, United States, 71103
United States, Maryland
University of Maryland/Baltimore
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Minnesota
Hennepin County Medical Center
Minneapolis, Minnesota, United States, 55415
United States, New York
State University of New York - Downstate Medical Center
Brooklyn, New York, United States, 11203
North Shore University Hospital
Manhasset, New York, United States, 11030
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
East Carolina University
Greenville, North Carolina, United States, 27834
United States, Ohio
Summa Health System
Akron, Ohio, United States, 44304-1619
United States, Pennsylvania
Penn State Hershey College of Medicine; Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Temple University Hospital
Philadelphia, Pennsylvania, United States, 19140
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15261
UPMC Shadyside Hospital
Pittsburgh, Pennsylvania, United States, 15232
Allegheny General Hospital
Pittsburgh, Pennsylvania, United States, 15212
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37403
United States, Texas
University Medical Center Brackenridge
Austin, Texas, United States, 78752
United States, Utah
Intermountain Medical Center
Salt Lake City, Utah, United States, 84157
University of Utah Health Sciences Center
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Derek C. Angus, MD, MPH University of Pittsburgh
Principal Investigator: John A. Kellum, MD University of Pittsburgh
Principal Investigator: Donald M. Yealy, MD University of Pittsburgh
  More Information

Additional Information:
Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00510835     History of Changes
Other Study ID Numbers: P50 GM076659
Study First Received: July 18, 2007
Last Updated: June 6, 2013
Health Authority: United States: Institutional Review Board
United States: Federal Government

Keywords provided by University of Pittsburgh:
septic shock
resuscitation
sepsis
cost-effectiveness
sepsis-induced organ dysfunction
early goal directed therapy
emergency medicine
critical care medicine

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

ClinicalTrials.gov processed this record on October 01, 2014