Preemptive Resuscitation for Eradication of Septic Shock

• 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: Christiana Care Health Services
• Information provided by (Responsible Party): Christiana Care Health Services

Study Description

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.

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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

Eligibility Criteria

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

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

Contacts and Locations

Locations

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

Investigators

• 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

Publications:

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.

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.

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.

• Responsible Party: Christiana Care Health Services
• ClinicalTrials.gov Identifier: NCT01449721
• Other Study ID Numbers: PRESHOCK
• First Posted: October 10, 2011
• Results First Posted: October 4, 2017
• Last Update Posted: October 4, 2017
• Last Verified: October 2017

Keywords provided by Christiana Care Health Services:

Sepsis; Multiple organ failure; Resuscitation

Additional relevant MeSH terms:

Sepsis; Toxemia; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes