Protocolized Care for Early Septic Shock

Sepsis Clinical Trial

— ProCESS  

Official title:

Protocolized Care for Early Septic Shock

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00510835
• Other study ID #: P50GM076659
• Status: Active, not recruiting
• Phase: N/A
• First received: July 18, 2007
• Last updated: June 6, 2013
• Start date: March 2008
• Est. completion date: December 2013

Study information

• Verified date: June 2013
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1351
• Est. completion date: December 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sepsis
• Septic Shock
• Severe Sepsis
• Shock
• Shock, Septic
• Toxemia

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Summa Health System	Akron	Ohio
United States	University Medical Center Brackenridge	Austin	Texas
United States	University of Maryland/Baltimore	Baltimore	Maryland
United States	University of Alabama	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	State University of New York - Downstate Medical Center	Brooklyn	New York
United States	Duke University Medical Center	Durham	North Carolina
United States	East Carolina University	Greenville	North Carolina
United States	Penn State Hershey College of Medicine; Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Methodist Research Institute	Indianapolis	Indiana
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	LA County & USC Medical Center	Los Angeles	California
United States	North Shore University Hospital	Manhasset	New York
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Norwalk Hospital	Norwalk	Connecticut
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Stanford University School of Medicine	Palo Alto	California
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Maricopa Medical Center	Phoenix	Arizona
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	UPMC Shadyside Hospital	Pittsburgh	Pennsylvania
United States	UC Davis Medical Center	Sacramento	California
United States	Intermountain Medical Center	Salt Lake City	Utah
United States	University of Utah Health Sciences Center	Salt Lake City	Utah
United States	Louisiana State University Health Sciences Center/Shreveport	Shreveport	Louisiana
United States	Tampa General Hospital	Tampa	Florida
United States	George Washington University Medical Center	Washington	District of Columbia
United States	Washington Hospital Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
University of Pittsburgh	National Institute of General Medical Sciences (NIGMS)

Country where clinical trial is conducted

United States, 

References & Publications (17)

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. — View Citation

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. Review. — View Citation

Dellinger RP. Cardiovascular management of septic shock. Crit Care Med. 2003 Mar;31(3):946-55. Review. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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

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. — View Citation

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. — View Citation

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

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. Erratum in: N Engl J Med. 2007 Jun 21;356(25):2660. — View Citation

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. — View Citation

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. Erratum in: Ann Emerg Med 1994 Dec;24(6):1208. — View Citation

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. — View Citation

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. Review. — View Citation

Yealy DM, Delbridge TR. The shock index: all that glitters... Ann Emerg Med. 1994 Oct;24(4):714-5. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hospital mortality		prior to discharge or 60 days, whichever comes first	No
Secondary	Changes in markers of inflammation, oxidative stress, cellular hypoxia and coagulation/thrombosis.		study hour 0, 6, 24 & 72	No
Secondary	Resource use and costs of alternative resuscitation strategies		at discharge or 60 days, whichever comes first	No

External Links

•   ProCESS Study Web Site