Clinical trial NCT00510835: Protocolized Care for Early Septic Shock
Official title: Protocolized Care for Early Septic Shock
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
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
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institute of General Medical Sciences (NIGMS)
First posted: 2007-08-02
Enrollment: 1351
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Hospital Mortality
timeFrame: prior to discharge or 60 days, whichever comes first
Secondary outcomes:
measure: Changes in Markers of Inflammation, Oxidative Stress, Cellular Hypoxia and Coagulation/Thrombosis.
timeFrame: study hour 0, 6, 24 & 72
measure: Resource Use and Costs of Alternative Resuscitation Strategies
timeFrame: at discharge or 60 days, whichever comes first
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Maricopa Medical Center
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Los Angeles
country: United States
facility: LA County & USC Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford University School of Medicine
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Norwalk
country: United States
facility: Norwalk Hospital
state: Connecticut
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Washington
country: United States
facility: George Washington University Medical Center
state: District of Columbia
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Methodist Research Institute
state: Indiana
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center/Shreveport
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland/Baltimore
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Brooklyn
country: United States
facility: State University of New York - Downstate Medical Center
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Akron
country: United States
facility: Summa Health System
state: Ohio
city: Hershey
country: United States
facility: Penn State Hershey College of Medicine; Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Shadyside Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: University Medical Center Brackenridge
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health Sciences Center
state: Utah
city: Salt Lake City
country: United States
facility: Intermountain Medical Center
state: Utah
Study officials:
affiliation: University of Pittsburgh
name: Derek C. Angus, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: John A. Kellum, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: Donald M. Yealy, MD
role: PRINCIPAL_INVESTIGATOR
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citation: 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.
citation: 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.
citation: 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.
citation: 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.