Preemptive Resuscitation for Eradication of Septic Shock

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Christiana Care Health Services Identifier:
First received: September 29, 2011
Last updated: July 16, 2015
Last verified: July 2015
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 Intervention
Severe Sepsis
Drug: Intravenous fluid

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Preemptive Empiric Resuscitation Protocol for the Prevention of Disease Progression in the Treatment of Sepsis

Resource links provided by NLM:

Further study details as provided by Christiana Care Health Services:

Primary Outcome Measures:
  • Organ failure [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Development of worsening organ failure (SOFA score increased by >1 point) over 72 hours.

Secondary Outcome Measures:
  • Mortality [ Time Frame: In-hospital ] [ Designated as safety issue: No ]
    All-cause in-hospital mortality (up to 1 year).

  • Volume overload [ Time Frame: 12 hours following treatment initiation ] [ Designated as safety issue: Yes ]

    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

Estimated Enrollment: 140
Study Start Date: September 2011
Estimated Study Completion Date: January 2016
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01449721

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
Study Chair: Alan Jones, MD University of Mississippi Medical Center
Principal Investigator: Ryan Arnold, MD Cooper University Hospital: Cooper Medical School of Rowan University
  More Information

Responsible Party: Christiana Care Health Services Identifier: NCT01449721     History of Changes
Other Study ID Numbers: PRESHOCK
Study First Received: September 29, 2011
Last Updated: July 16, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Christiana Care Health Services:
Multiple organ failure

Additional relevant MeSH terms:
Pathologic Processes
Systemic Inflammatory Response Syndrome processed this record on November 27, 2015