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Preemptive Resuscitation for Eradication of Septic Shock

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ClinicalTrials.gov Identifier: NCT01449721
Recruitment Status : Completed
First Posted : October 10, 2011
Results First Posted : October 4, 2017
Last Update Posted : October 4, 2017
Sponsor:
Information provided by (Responsible Party):
Christiana Care Health Services

Tracking Information
First Submitted Date  ICMJE September 29, 2011
First Posted Date  ICMJE October 10, 2011
Results First Submitted Date  ICMJE November 30, 2016
Results First Posted Date  ICMJE October 4, 2017
Last Update Posted Date October 4, 2017
Study Start Date  ICMJE September 2011
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 2, 2017)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 7, 2011)
Organ failure [ Time Frame: 72 hours ]
Development of worsening organ failure (SOFA score increased by >1 point) over 72 hours.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 2, 2017)
  • 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.
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: October 7, 2011)
  • Mortality [ Time Frame: In-hospital ]
    All-cause in-hospital mortality (up to 1 year).
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Preemptive Resuscitation for Eradication of Septic Shock
Official Title  ICMJE Preemptive Empiric Resuscitation Protocol for the Prevention of Disease Progression in the Treatment of Sepsis
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Sepsis
  • Severe Sepsis
Intervention  ICMJE Drug: Intravenous fluid
0.9% Sodium chloride intravenous fluid
Other Name: Normal saline
Study Arms  ICMJE
  • 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
    Intervention: Drug: Intravenous fluid
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 2, 2017)
142
Original Estimated Enrollment  ICMJE
 (submitted: October 7, 2011)
140
Actual Study Completion Date  ICMJE January 2016
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01449721
Other Study ID Numbers  ICMJE PRESHOCK
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Christiana Care Health Services
Study Sponsor  ICMJE Christiana Care Health Services
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Alan Jones, MD University of Mississippi Medical Center
Principal Investigator: Ryan Arnold, MD Cooper University Hospital: Cooper Medical School of Rowan University
PRS Account Christiana Care Health Services
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP