Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
NA
1351 participants
INTERVENTIONAL
2008-03-31
2013-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Protocol-driven Hemodynamic Support for Patients With Septic Shock
NCT00335907
Preemptive Resuscitation for Eradication of Septic Shock
NCT01449721
POCUS-Guided Esmolol in Septic Shock: A Pilot RCT
NCT07313605
Comparison of ECMO Use and Conventional Treatment in Adults With Septic Shock
NCT01685112
Fluid Intolerance Signals as Safety Limits to Prevent Fluid-induced Harm During Septic Shock Resuscitation
NCT06568744
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
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.
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.
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.
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.
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.
Usual Care (UC)
Attending physicians will provide routine care to subjects. Study measurements and treatments will be based on the physicians'/sites' standard practices.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
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.
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.
Usual Care (UC)
Attending physicians will provide routine care to subjects. Study measurements and treatments will be based on the physicians'/sites' standard practices.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Institute of General Medical Sciences (NIGMS)
NIH
University of Pittsburgh
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Derek C. Angus, MD, MPH
Chair, Critical Care Medicine
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Derek C. Angus, MD, MPH
Role: PRINCIPAL_INVESTIGATOR
University of Pittsburgh
John A. Kellum, MD
Role: PRINCIPAL_INVESTIGATOR
University of Pittsburgh
Donald M. Yealy, MD
Role: PRINCIPAL_INVESTIGATOR
University of Pittsburgh
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
University of Alabama
Birmingham, Alabama, United States
Maricopa Medical Center
Phoenix, Arizona, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
LA County & USC Medical Center
Los Angeles, California, United States
Stanford University School of Medicine
Palo Alto, California, United States
UC Davis Medical Center
Sacramento, California, United States
Norwalk Hospital
Norwalk, Connecticut, United States
Washington Hospital Center
Washington D.C., District of Columbia, United States
George Washington University Medical Center
Washington D.C., District of Columbia, United States
Tampa General Hospital
Tampa, Florida, United States
Advocate Christ Medical Center
Oak Lawn, Illinois, United States
Methodist Research Institute
Indianapolis, Indiana, United States
Louisiana State University Health Sciences Center/Shreveport
Shreveport, Louisiana, United States
University of Maryland/Baltimore
Baltimore, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Brigham and Women's Hospital
Boston, Massachusetts, United States
Hennepin County Medical Center
Minneapolis, Minnesota, United States
State University of New York - Downstate Medical Center
Brooklyn, New York, United States
North Shore University Hospital
Manhasset, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
East Carolina University
Greenville, North Carolina, United States
Summa Health System
Akron, Ohio, United States
Penn State Hershey College of Medicine; Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States
Temple University Hospital
Philadelphia, Pennsylvania, United States
Allegheny General Hospital
Pittsburgh, Pennsylvania, United States
UPMC Shadyside Hospital
Pittsburgh, Pennsylvania, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
University Medical Center Brackenridge
Austin, Texas, United States
University of Utah Health Sciences Center
Salt Lake City, Utah, United States
Intermountain Medical Center
Salt Lake City, Utah, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
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.
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.
Kochanek KD, Smith BL. Deaths: preliminary data for 2002. Natl Vital Stat Rep. 2004 Feb 11;52(13):1-47.
O'Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biometrics. 1979 Sep;35(3):549-56.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Yealy DM, Delbridge TR. The shock index: all that glitters.. Ann Emerg Med. 1994 Oct;24(4):714-5. No abstract available.
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.
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.
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.
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.
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.
Related Links
Access external resources that provide additional context or updates about the study.
ProCESS Study Web Site
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.