Preemptive Resuscitation for Eradication of Septic Shock

Sepsis Clinical Trial

Official title:

Preemptive Empiric Resuscitation Protocol for the Prevention of Disease Progression in the Treatment of Sepsis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01449721
• Other study ID #: PRESHOCK
• Status: Completed
• Phase: N/A
• First received: September 29, 2011
• Last updated: October 2, 2017
• Start date: September 2011
• Est. completion date: January 2016

Study information

• Verified date: October 2017
• Source: Christiana Care Health Services
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the ability of an empiric resuscitation strategy compared to standard care to decrease the incidence of organ failure in normotensive sepsis patients.

Description:

Sepsis is a challenging and elusive entity with a high mortality rate. As a syndrome, clinicians are challenged to distinguish individuals with systemic infection warranting further interventions from lower severity patients. Sepsis is now recognized as a time-sensitive emergency, as patients stand the best chance for survival when effective therapeutic interventions are delivered as early as possible.

Recent data has shown that in-hospital disease progression from sepsis to septic shock is associated with a higher risk of morbidity and mortality than those with shock on initial presentation. Yet, even when identified and treated with early aggressive interventions, the development of septic shock is still associated with a mortality rate of 25-40%.

Although the presence of sustained arterial hypotension or serum lactate elevation (>4.0 mmol/L) are the currently recommended threshold to define the presence of overt shock and the need for aggressive resuscitation, the investigators have shown that, in patients with systemic infection, a moderate lactate elevation (2.0-3.9 mmol/L) is a common occurrence and an important warning sign for the increased risk of disease progression and death. Sepsis with an elevated lactate between 2.0-3.9, referred to as the "PRE-SHOCK" state, identifies this population of patients at-risk for poor outcome. Current guidelines for sepsis management do not recommend any specific resuscitation measures or therapies for this at-risk population. This study marks the first in a series of investigations addressing the PRE-SHOCK population to further define the adverse events within this cohort and to investigate novel interventions to improve outcomes.

The investigators hypothesize that an early quantitative resuscitation strategy using a protocol-directed IV fluid resuscitation will result in a significant reduction in the development of worsening organ failure (including shock) and mortality compared to standard care.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 142
• Est. completion date: January 2016
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Emergency department patient with suspected or confirmed infection as primary reason for admission

• Serum venous lactate 2.0 - 3.9 mmol/L

• Hospital admission planned

Exclusion Criteria:

• Age < 18 years

• Pregnancy

• Serum lactate = 4.0 mmol/L

• Any vasopressor or inotrope requirement

• Mechanical ventilation or non-invasive positive pressure ventilation

• Chronic end-stage renal disease requiring hemodialysis

• Pulmonary edema as diagnosed by the primary care team

• Requirement for surgery within the treatment protocol timeframe

• Inability to obtain informed consent from subject or surrogate

• Patient to receive comfort measures only

Related Conditions & MeSH terms

• Sepsis
• Severe Sepsis
• Toxemia

Intervention

Drug:
• Intravenous fluid
0.9% Sodium chloride intravenous fluid

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Cooper University Hospital:Cooper Medical School of Rowan University	Camden	New Jersey
United States	Detroit Receiving Hospital/University Health Center	Detroit	Michigan
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Christiana Care Health System	Newark	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Christiana Care Health Services

Country where clinical trial is conducted

United States, 

References & Publications (3)

Glickman SW, Cairns CB, Otero RM, Woods CW, Tsalik EL, Langley RJ, van Velkinburgh JC, Park LP, Glickman LT, Fowler VG Jr, Kingsmore SF, Rivers EP. Disease progression in hemodynamically stable patients presenting to the emergency department with sepsis. Acad Emerg Med. 2010 Apr;17(4):383-90. doi: 10.1111/j.1553-2712.2010.00664.x. — View Citation

Mikkelsen ME, Miltiades AN, Gaieski DF, Goyal M, Fuchs BD, Shah CV, Bellamy SL, Christie JD. Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock. Crit Care Med. 2009 May;37(5):1670-7. doi: 10.1097/CCM.0b013e31819fcf68. — View Citation

Sakr Y, Vincent JL, Schuerholz T, Filipescu D, Romain A, Hjelmqvist H, Reinhart K. Early- versus late-onset shock in European intensive care units. Shock. 2007 Dec;28(6):636-643. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Worsening Organ System Dysfunction Defined by SOFA Score Increase = 1	Development of worsening organ failure defined by the Sequential Organ Failure Assessment (SOFA) score. The SOFA score defines the presence and severity of dysfunction within 6 organ systems (cardiovascular, respiratory, coagulation, liver, renal, and nervous system) with a value of "0" for assigned to normal function to a maximum value of "4" for severe dysfunction in each of the organ systems. Each component of the SOFA score is added together, ranging from "0" indicating no organ dysfunction in any of the 6 organ systems, to "24" indicating maximal organ dysfunction across all 6 organ systems.; Within this trial, the occurrence of organ failure was defined by any increase in the total SOFA score by = 1 point over the first 72 hours after randomization.	72 hours
Secondary	In-hospital Mortality	Any occurrence of mortality while the participant is in-hospital is counted as an outcome.	In-hospital discharge or up to maximum 30 days
Secondary	Number of Participants With Experiencing Complications Related to Intravascular Volume Overload	Composite safety endpoint: Premature termination of the protocol-directed intravenous fluid administration by the investigator or primary physician due to presumed volume overload; Administration of intravenous diuretic for acute pulmonary edema; Respiratory failure requiring ventilatory assistance (BiPAP, CPAP, or mechanical ventilation) secondary to pulmonary edema per primary care team	12 hours following treatment initiation