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
|Condition or disease||Intervention/treatment||Phase|
|Sepsis Severe Sepsis||Drug: Intravenous fluid||Not Applicable|
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||142 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
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
- 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.
- 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
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|
|Study Chair:||Alan Jones, MD||University of Mississippi Medical Center|
|Principal Investigator:||Ryan Arnold, MD||Cooper University Hospital: Cooper Medical School of Rowan University|