Protocolized Care for Early Septic Shock

NCT00510835 | Completed Results DMC

• 1 other identifier: P50GM076659
• Study Type: interventional
• Target: 1,351
• Locations: 1 country
• Sites: 31

Brief Summary

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.

Conditions

Sepsis; Severe Sepsis; Septic Shock

Keywords

septic shock; resuscitation; sepsis; cost-effectiveness; sepsis-induced organ dysfunction; early goal directed therapy; emergency medicine; critical care medicine

Outcome Measures

Primary Outcomes (1)

• Hospital Mortality

  The primary study outcome is hospital mortality (defined as the number of deaths prior to discharge or 60 days, whichever comes first). The secondary outcomes are duration of survival (90 day and 1 year) and clinical evidence of organ dysfunction.

  prior to discharge or 60 days, whichever comes first

Secondary Outcomes (2)

• Changes in Markers of Inflammation, Oxidative Stress, Cellular Hypoxia and Coagulation/Thrombosis.

  study hour 0, 6, 24 & 72

• Resource Use and Costs of Alternative Resuscitation Strategies

  at discharge or 60 days, whichever comes first

Study Arms (3)

1

EXPERIMENTAL

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)

2

EXPERIMENTAL

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)

3

ACTIVE COMPARATOR

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)

Interventions

Early Goal Directed Therapy (EGDT) PROCEDURE

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.

1

Protocolized Standard Care (PSC) PROCEDURE

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.

2

Usual Care (UC) PROCEDURE

Attending physicians will provide routine care to subjects. Study measurements and treatments will be based on the physicians'/sites' standard practices.

3

Eligibility Criteria

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

You may qualify if:

• 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)

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

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (31)

University of Alabama

Birmingham, Alabama, 35249, United States

Location

Maricopa Medical Center

Phoenix, Arizona, 85008, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

LA County & USC Medical Center

Los Angeles, California, 90033, United States

Location

Stanford University School of Medicine

Palo Alto, California, 94025, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

Norwalk Hospital

Norwalk, Connecticut, 06856, United States

Location

Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

George Washington University Medical Center

Washington D.C., District of Columbia, 20037, United States

Location

Tampa General Hospital

Tampa, Florida, 33601, United States

Location

Advocate Christ Medical Center

Oak Lawn, Illinois, 60453, United States

Location

Methodist Research Institute

Indianapolis, Indiana, 46202, United States

Location

Louisiana State University Health Sciences Center/Shreveport

Shreveport, Louisiana, 71103, United States

Location

University of Maryland/Baltimore

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

State University of New York - Downstate Medical Center

Brooklyn, New York, 11203, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

East Carolina University

Greenville, North Carolina, 27834, United States

Location

Summa Health System

Akron, Ohio, 44304-1619, United States

Location

Penn State Hershey College of Medicine; Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

UPMC Shadyside Hospital

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15261, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37403, United States

Location

University Medical Center Brackenridge

Austin, Texas, 78752, United States

Location

University of Utah Health Sciences Center

Salt Lake City, Utah, 84132, United States

Location

Intermountain Medical Center

Salt Lake City, Utah, 84157, United States

Location

Related Publications (21)

• Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. doi: 10.1056/NEJMoa010307.

  PMID: 11794169 BACKGROUND

• Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001 Jul;29(7):1303-10. doi: 10.1097/00003246-200107000-00002.

  PMID: 11445675 BACKGROUND

• Kochanek KD, Smith BL. Deaths: preliminary data for 2002. Natl Vital Stat Rep. 2004 Feb 11;52(13):1-47.

  PMID: 14998175 BACKGROUND

• O'Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biometrics. 1979 Sep;35(3):549-56.

  PMID: 497341 BACKGROUND

• Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992 Jun;101(6):1644-55. doi: 10.1378/chest.101.6.1644.

  PMID: 1303622 BACKGROUND

• Rivers EP, Ander DS, Powell D. Central venous oxygen saturation monitoring in the critically ill patient. Curr Opin Crit Care. 2001 Jun;7(3):204-11. doi: 10.1097/00075198-200106000-00011.

  PMID: 11436529 BACKGROUND

• Feezor RJ, Baker HV, Mindrinos M, Hayden D, Tannahill CL, Brownstein BH, Fay A, MacMillan S, Laramie J, Xiao W, Moldawer LL, Cobb JP, Laudanski K, Miller-Graziano CL, Maier RV, Schoenfeld D, Davis RW, Tompkins RG; Inflammation and Host Response to Injury, Large-Scale Collaborative Research Program. Whole blood and leukocyte RNA isolation for gene expression analyses. Physiol Genomics. 2004 Nov 17;19(3):247-54. doi: 10.1152/physiolgenomics.00020.2004.

  PMID: 15548831 BACKGROUND

• Maki DG, Stolz SM, Wheeler S, Mermel LA. Prevention of central venous catheter-related bloodstream infection by use of an antiseptic-impregnated catheter. A randomized, controlled trial. Ann Intern Med. 1997 Aug 15;127(4):257-66. doi: 10.7326/0003-4819-127-4-199708150-00001.

  PMID: 9265424 BACKGROUND

• Pronovost P, Needham D, Berenholtz S, Sinopoli D, Chu H, Cosgrove S, Sexton B, Hyzy R, Welsh R, Roth G, Bander J, Kepros J, Goeschel C. An intervention to decrease catheter-related bloodstream infections in the ICU. N Engl J Med. 2006 Dec 28;355(26):2725-32. doi: 10.1056/NEJMoa061115.

  PMID: 17192537 BACKGROUND

• McGee WT, Ackerman BL, Rouben LR, Prasad VM, Bandi V, Mallory DL. Accurate placement of central venous catheters: a prospective, randomized, multicenter trial. Crit Care Med. 1993 Aug;21(8):1118-23. doi: 10.1097/00003246-199308000-00008.

  PMID: 8339574 BACKGROUND

• Goodnough LT, Brecher ME, Kanter MH, AuBuchon JP. Transfusion medicine. First of two parts--blood transfusion. N Engl J Med. 1999 Feb 11;340(6):438-47. doi: 10.1056/NEJM199902113400606. No abstract available.

  PMID: 9971869 BACKGROUND

• Dodd RY, Notari EP 4th, Stramer SL. Current prevalence and incidence of infectious disease markers and estimated window-period risk in the American Red Cross blood donor population. Transfusion. 2002 Aug;42(8):975-9. doi: 10.1046/j.1537-2995.2002.00174.x.

  PMID: 12385406 BACKGROUND

• Dellinger RP. Cardiovascular management of septic shock. Crit Care Med. 2003 Mar;31(3):946-55. doi: 10.1097/01.CCM.0000057403.73299.A6. No abstract available.

  PMID: 12627010 BACKGROUND

• Hollenberg SM, Ahrens TS, Annane D, Astiz ME, Chalfin DB, Dasta JF, Heard SO, Martin C, Napolitano LM, Susla GM, Totaro R, Vincent JL, Zanotti-Cavazzoni S. Practice parameters for hemodynamic support of sepsis in adult patients: 2004 update. Crit Care Med. 2004 Sep;32(9):1928-48. doi: 10.1097/01.ccm.0000139761.05492.d6.

  PMID: 15343024 BACKGROUND

• Rady MY, Smithline HA, Blake H, Nowak R, Rivers E. A comparison of the shock index and conventional vital signs to identify acute, critical illness in the emergency department. Ann Emerg Med. 1994 Oct;24(4):685-90. doi: 10.1016/s0196-0644(94)70279-9.

  PMID: 8092595 BACKGROUND

• Yealy DM, Delbridge TR. The shock index: all that glitters.. Ann Emerg Med. 1994 Oct;24(4):714-5. No abstract available.

  PMID: 8092601 BACKGROUND

• Rady MY, Rivers EP, Nowak RM. Resuscitation of the critically ill in the ED: responses of blood pressure, heart rate, shock index, central venous oxygen saturation, and lactate. Am J Emerg Med. 1996 Mar;14(2):218-25. doi: 10.1016/s0735-6757(96)90136-9.

  PMID: 8924150 BACKGROUND

• Fiorentino M, Xu Z, Smith A, Singbartl K, Palevsky PM, Chawla LS, Huang DT, Yealy DM, Angus DC, Kellum JA; ProCESS and ProGReSS-AKI Investigators. Serial Measurement of Cell-Cycle Arrest Biomarkers [TIMP-2] . [IGFBP7] and Risk for Progression to Death, Dialysis, or Severe Acute Kidney Injury in Patients with Septic Shock. Am J Respir Crit Care Med. 2020 Nov 1;202(9):1262-1270. doi: 10.1164/rccm.201906-1197OC.

  PMID: 32584598 DERIVED

• Massey MJ, Hou PC, Filbin M, Wang H, Ngo L, Huang DT, Aird WC, Novack V, Trzeciak S, Yealy DM, Kellum JA, Angus DC, Shapiro NI; ProCESS investigators. Microcirculatory perfusion disturbances in septic shock: results from the ProCESS trial. Crit Care. 2018 Nov 20;22(1):308. doi: 10.1186/s13054-018-2240-5.

  PMID: 30458880 DERIVED

• 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 DERIVED

• ProCESS Investigators; Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, Terndrup T, Wang HE, Hou PC, LoVecchio F, Filbin MR, Shapiro NI, Angus DC. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014 May 1;370(18):1683-93. doi: 10.1056/NEJMoa1401602. Epub 2014 Mar 18.

  PMID: 24635773 DERIVED

Related Links

• ProCESS Study Web Site

MeSH Terms

Conditions

Sepsis; Shock, Septic

Interventions

Early Goal-Directed Therapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Critical Care; Patient Care; Therapeutics

Results Point of Contact

• Title: Derek C. Angus, MD, MPH, FRCP
• Organization: UPittsburgh

angusdc@ccm.upmc.edu

(412) 647-6965

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair, Critical Care Medicine

Study Record Dates

• First Submitted: July 18, 2007
• First Posted: August 2, 2007
• Study Start: March 1, 2008
• Primary Completion: July 1, 2013
• Study Completion: December 1, 2013
• Last Updated: January 26, 2017
• Results First Posted: January 26, 2017

Record last verified: 2016-12

Locations

US (31)