Preemptive Resuscitation for Eradication of Septic Shock

NCT ID: NCT01449721

Last Updated: 2017-10-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 142 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2016-01-31

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.

Conditions

Sepsis; Severe Sepsis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Control

Standard medical care by the primary treatment team.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventional arm

Protocolized empiric resuscitation delivering weight-based intravenous fluid resuscitation targeting lactate normalization

Group Type: EXPERIMENTAL

Intravenous fluid

Intervention Type: DRUG

0.9% Sodium chloride intravenous fluid

Interventions

Intravenous fluid

0.9% Sodium chloride intravenous fluid

Intervention Type: DRUG

Other Intervention Names

Normal saline

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Christiana Care Health Services

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alan Jones, MD

Role: STUDY_CHAIR

University of Mississippi Medical Center

Ryan Arnold, MD

Role: PRINCIPAL_INVESTIGATOR

Cooper University Hospital: Cooper Medical School of Rowan University

Locations

Christiana Care Health System

Newark, Delaware, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Detroit Receiving Hospital/University Health Center

Detroit, Michigan, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Cooper University Hospital:Cooper Medical School of Rowan University

Camden, New Jersey, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 18092378 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19325467 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20370777 (View on PubMed)

Other Identifiers

PRESHOCK

Identifier Type: -

Identifier Source: org_study_id