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Preemptive Resuscitation for Eradication of Septic Shock

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01449721
Recruitment Status : Completed
First Posted : October 10, 2011
Results First Posted : October 4, 2017
Last Update Posted : October 4, 2017
Information provided by (Responsible Party):
Christiana Care Health Services

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.

Condition or disease Intervention/treatment Phase
Sepsis Severe Sepsis Drug: Intravenous fluid Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 142 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Preemptive Empiric Resuscitation Protocol for the Prevention of Disease Progression in the Treatment of Sepsis
Study Start Date : September 2011
Actual Primary Completion Date : January 2015
Actual Study Completion Date : January 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sepsis

Arm Intervention/treatment
No Intervention: Control
Standard medical care by the primary treatment team.
Experimental: Interventional arm
Protocolized empiric resuscitation delivering weight-based intravenous fluid resuscitation targeting lactate normalization
Drug: Intravenous fluid
0.9% Sodium chloride intravenous fluid
Other Name: Normal saline

Primary Outcome Measures :
  1. Number of Participants With Worsening Organ System Dysfunction Defined by SOFA Score Increase ≥ 1 [ Time Frame: 72 hours ]

    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.

Secondary Outcome Measures :
  1. In-hospital Mortality [ Time Frame: In-hospital discharge or up to maximum 30 days ]
    Any occurrence of mortality while the participant is in-hospital is counted as an outcome.

  2. Number of Participants With Experiencing Complications Related to Intravascular Volume Overload [ Time Frame: 12 hours following treatment initiation ]

    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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01449721

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United States, Delaware
Christiana Care Health System
Newark, Delaware, United States, 19718
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Michigan
Detroit Receiving Hospital/University Health Center
Detroit, Michigan, United States, 48201
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
United States, New Jersey
Cooper University Hospital:Cooper Medical School of Rowan University
Camden, New Jersey, United States, 08103
Sponsors and Collaborators
Christiana Care Health Services
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Study Chair: Alan Jones, MD University of Mississippi Medical Center
Principal Investigator: Ryan Arnold, MD Cooper University Hospital: Cooper Medical School of Rowan University
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Responsible Party: Christiana Care Health Services Identifier: NCT01449721    
Other Study ID Numbers: PRESHOCK
First Posted: October 10, 2011    Key Record Dates
Results First Posted: October 4, 2017
Last Update Posted: October 4, 2017
Last Verified: October 2017
Keywords provided by Christiana Care Health Services:
Multiple organ failure
Additional relevant MeSH terms:
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Systemic Inflammatory Response Syndrome
Pathologic Processes