Trial Outcomes & Findings for Preemptive Resuscitation for Eradication of Septic Shock (NCT NCT01449721)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

142 participants

Primary outcome timeframe

72 hours

Results posted on

2017-10-04

Participant Flow

Prior to interventional arm of the trial, a 5-month observational period was performed identifying 94 patients in the control arm. At the initiation of the interventional study, subjects were randomized in a 2:1 ratio to intervention:control, enrolling an additional 18 patients to the control arm, and 30 patients to the intervention.

Participant milestones

Participant milestones
Measure	Control Standard medical care by the primary treatment team.	Interventional Arm Protocolized empiric resuscitation delivering weight-based intravenous fluid resuscitation targeting lactate normalization Intravenous fluid: 0.9% Sodium chloride intravenous fluid
Overall Study STARTED	112	30
Overall Study COMPLETED	112	28
Overall Study NOT COMPLETED	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Control Standard medical care by the primary treatment team.	Interventional Arm Protocolized empiric resuscitation delivering weight-based intravenous fluid resuscitation targeting lactate normalization Intravenous fluid: 0.9% Sodium chloride intravenous fluid
Overall Study Physician Decision	0	1

Baseline Characteristics

Preemptive Resuscitation for Eradication of Septic Shock

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Control n=112 Participants Standard medical care by the primary treatment team.	Interventional Arm n=30 Participants Protocolized empiric resuscitation delivering weight-based intravenous fluid resuscitation targeting lactate normalization Intravenous fluid: 0.9% Sodium chloride intravenous fluid	Total n=142 Participants Total of all reporting groups
Age, Continuous	58.3 years STANDARD_DEVIATION 15 • n=5 Participants	56.8 years STANDARD_DEVIATION 16 • n=7 Participants	58 years STANDARD_DEVIATION 15 • n=5 Participants
Sex: Female, Male Female	51 Participants n=5 Participants	12 Participants n=7 Participants	63 Participants n=5 Participants
Sex: Female, Male Male	61 Participants n=5 Participants	18 Participants n=7 Participants	79 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Control n=112 Participants Standard medical care by the primary treatment team.	Interventional Arm n=30 Participants Protocolized empiric resuscitation delivering weight-based intravenous fluid resuscitation targeting lactate normalization Intravenous fluid: 0.9% Sodium chloride intravenous fluid
Number of Participants With Worsening Organ System Dysfunction Defined by SOFA Score Increase ≥ 1	34 Participants	20 Participants

SECONDARY outcome

Timeframe: In-hospital discharge or up to maximum 30 days

Any occurrence of mortality while the participant is in-hospital is counted as an outcome.

Outcome measures

Outcome measures
Measure	Control n=112 Participants Standard medical care by the primary treatment team.	Interventional Arm n=30 Participants Protocolized empiric resuscitation delivering weight-based intravenous fluid resuscitation targeting lactate normalization Intravenous fluid: 0.9% Sodium chloride intravenous fluid
In-hospital Mortality	4 Participants	0 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Control n=112 Participants Standard medical care by the primary treatment team.	Interventional Arm n=30 Participants Protocolized empiric resuscitation delivering weight-based intravenous fluid resuscitation targeting lactate normalization Intravenous fluid: 0.9% Sodium chloride intravenous fluid
Number of Participants With Experiencing Complications Related to Intravascular Volume Overload	4 Participants	3 Participants

Adverse Events

Control

Serious events: 4 serious events

Other events: 0 other events

Deaths: 4 deaths

Interventional Arm

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Control n=112 participants at risk Standard medical care by the primary treatment team.	Interventional Arm n=30 participants at risk Protocolized empiric resuscitation delivering weight-based intravenous fluid resuscitation targeting lactate normalization Intravenous fluid: 0.9% Sodium chloride intravenous fluid
Respiratory, thoracic and mediastinal disorders Respiratory failure requiring mechanical intervention	3.6% 4/112 • Number of events 4 • Respiratory failure occurring within 24 hours of enrollment. Fluid overload occurring within 24 hours of enrollment. Mortality occurring at anytime within hospital stay.	6.7% 2/30 • Number of events 2 • Respiratory failure occurring within 24 hours of enrollment. Fluid overload occurring within 24 hours of enrollment. Mortality occurring at anytime within hospital stay.
Vascular disorders Intravascular fluid overload	0.00% 0/112 • Respiratory failure occurring within 24 hours of enrollment. Fluid overload occurring within 24 hours of enrollment. Mortality occurring at anytime within hospital stay.	6.7% 2/30 • Number of events 2 • Respiratory failure occurring within 24 hours of enrollment. Fluid overload occurring within 24 hours of enrollment. Mortality occurring at anytime within hospital stay.
General disorders Mortality	3.6% 4/112 • Number of events 4 • Respiratory failure occurring within 24 hours of enrollment. Fluid overload occurring within 24 hours of enrollment. Mortality occurring at anytime within hospital stay.	0.00% 0/30 • Respiratory failure occurring within 24 hours of enrollment. Fluid overload occurring within 24 hours of enrollment. Mortality occurring at anytime within hospital stay.

Other adverse events

Adverse event data not reported

Additional Information

Ryan Arnold, MD, Director of Research, Emergency Medicine

Christiana Care Health System

Phone: 302-733-5108

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place