Clinical trial NCT01449721: Preemptive Resuscitation for Eradication of Septic Shock
Official title: Preemptive Empiric Resuscitation Protocol for the Prevention of Disease Progression in the Treatment of Sepsis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sepsis
Severe Sepsis
Keywords: Sepsis
Multiple organ failure
Resuscitation
Lead sponsor: Christiana Care Health Services
Sponsor class: OTHER
First posted: 2011-10-10
Enrollment: 142
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 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Worsening Organ System Dysfunction Defined by SOFA Score Increase ≥ 1
timeFrame: 72 hours
Secondary outcomes:
measure: In-hospital Mortality
timeFrame: In-hospital discharge or up to maximum 30 days
measure: Number of Participants With Experiencing Complications Related to Intravascular Volume Overload
timeFrame: 12 hours following treatment initiation
Other outcomes:
Locations:
city: Newark
country: United States
facility: Christiana Care Health System
state: Delaware
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Detroit Receiving Hospital/University Health Center
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Camden
country: United States
facility: Cooper University Hospital:Cooper Medical School of Rowan University
state: New Jersey
Study officials:
affiliation: University of Mississippi Medical Center
name: Alan Jones, MD
role: STUDY_CHAIR
affiliation: Cooper University Hospital: Cooper Medical School of Rowan University
name: Ryan Arnold, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: 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.