Trial Outcomes & Findings for The Randomized Controlled Trial of Inferior Vena Cava Ultrasound-guided Fluid Management in Septic Shock Resuscitation (NCT NCT03020407)
NCT ID: NCT03020407
Last Updated: 2021-09-22
Results Overview
30-day mortality related to septic shock
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
211 participants
Primary outcome timeframe
30 day after randomization
Results posted on
2021-09-22
Participant Flow
Participant milestones
| Measure |
IVC Ultrasound-guided
The treating physician will promptly assess the IVC diameter to obtain the collapsibility index (IVCCI) (or distensibility index, IVCDI) of an eligible patient. A previous study showed that IVCCI \> 40% were strongly associated with fluid responsiveness. Accordingly, the patient will be given 10 ml/kg of bolus of 0.9% normal saline solution (NSS) each time when the IVCCI \> 40% is discovered and serial measurements will be done after each intravenous bolus is achieved until the IVCCI \< 40 % during our protocol. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
IVC Ultrasound-guided: IVC is identified in longitudinal section in the subcostal area of a patient using the curvilinear probe of standard ultrasound. The selected area of IVC diameter measurement is set at 2 centimeters distal to the confluence of hepatic vein by M-mode coupled by two-dimensional mode on frozen screen images using the Sonosite® X-porte.
Antibiotics: Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
Vasopressor: The threshold to the need of a vasopressor is set at mean arterial pressure below 65 mmHg if a patient's condition does not response to the fluid therapy.
|
Usual Care
Patients will be promptly and empirically treated by 30 ml/kg loading of NSS in this treatment arm. After the NSS bolus, treatment with either the additional intravenous fluid or a vasopressor is given depended on physicians' discretion during the 6-hour study period. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
|
|---|---|---|
|
Overall Study
STARTED
|
105
|
106
|
|
Overall Study
COMPLETED
|
101
|
101
|
|
Overall Study
NOT COMPLETED
|
4
|
5
|
Reasons for withdrawal
| Measure |
IVC Ultrasound-guided
The treating physician will promptly assess the IVC diameter to obtain the collapsibility index (IVCCI) (or distensibility index, IVCDI) of an eligible patient. A previous study showed that IVCCI \> 40% were strongly associated with fluid responsiveness. Accordingly, the patient will be given 10 ml/kg of bolus of 0.9% normal saline solution (NSS) each time when the IVCCI \> 40% is discovered and serial measurements will be done after each intravenous bolus is achieved until the IVCCI \< 40 % during our protocol. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
IVC Ultrasound-guided: IVC is identified in longitudinal section in the subcostal area of a patient using the curvilinear probe of standard ultrasound. The selected area of IVC diameter measurement is set at 2 centimeters distal to the confluence of hepatic vein by M-mode coupled by two-dimensional mode on frozen screen images using the Sonosite® X-porte.
Antibiotics: Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
Vasopressor: The threshold to the need of a vasopressor is set at mean arterial pressure below 65 mmHg if a patient's condition does not response to the fluid therapy.
|
Usual Care
Patients will be promptly and empirically treated by 30 ml/kg loading of NSS in this treatment arm. After the NSS bolus, treatment with either the additional intravenous fluid or a vasopressor is given depended on physicians' discretion during the 6-hour study period. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
1
|
|
Overall Study
Lost to Follow-up
|
2
|
3
|
|
Overall Study
Protocol Violation
|
0
|
1
|
Baseline Characteristics
The Randomized Controlled Trial of Inferior Vena Cava Ultrasound-guided Fluid Management in Septic Shock Resuscitation
Baseline characteristics by cohort
| Measure |
IVC Ultrasound-guided
n=101 Participants
The treating physician will promptly assess the IVC diameter to obtain the collapsibility index (IVCCI) (or distensibility index, IVCDI) of an eligible patient. A previous study showed that IVCCI \> 40% were strongly associated with fluid responsiveness. Accordingly, the patient will be given 10 ml/kg of bolus of 0.9% normal saline solution (NSS) each time when the IVCCI \> 40% is discovered and serial measurements will be done after each intravenous bolus is achieved until the IVCCI \< 40 % during our protocol. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
IVC Ultrasound-guided: IVC is identified in longitudinal section in the subcostal area of a patient using the curvilinear probe of standard ultrasound. The selected area of IVC diameter measurement is set at 2 centimeters distal to the confluence of hepatic vein by M-mode coupled by two-dimensional mode on frozen screen images using the Sonosite® X-porte.
Antibiotics: Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
Vasopressor: The threshold to the need of a vasopressor is set at mean arterial pressure below 65 mmHg if a patient's condition does not response to the fluid therapy.
|
Usual Care
n=101 Participants
Patients will be promptly and empirically treated by 30 ml/kg loading of NSS in this treatment arm. After the NSS bolus, treatment with either the additional intravenous fluid or a vasopressor is given depended on physicians' discretion during the 6-hour study period. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
|
Total
n=202 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
47 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
96 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
54 Participants
n=5 Participants
|
52 Participants
n=7 Participants
|
106 Participants
n=5 Participants
|
|
Age, Continuous
|
65.3 years
STANDARD_DEVIATION 20.1 • n=5 Participants
|
63.7 years
STANDARD_DEVIATION 16.8 • n=7 Participants
|
64.5 years
STANDARD_DEVIATION 18.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
48 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
86 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
53 Participants
n=5 Participants
|
63 Participants
n=7 Participants
|
116 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
101 Participants
n=5 Participants
|
101 Participants
n=7 Participants
|
202 Participants
n=5 Participants
|
|
Region of Enrollment
Thailand
|
101 Participants
n=5 Participants
|
101 Participants
n=7 Participants
|
202 Participants
n=5 Participants
|
|
Patients with infections
|
101 Participants
n=5 Participants
|
101 Participants
n=7 Participants
|
202 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 30 day after randomization30-day mortality related to septic shock
Outcome measures
| Measure |
IVC Ultrasound-guided
n=101 Participants
The treating physician will promptly assess the IVC diameter to obtain the collapsibility index (IVCCI) (or distensibility index, IVCDI) of an eligible patient. A previous study showed that IVCCI \> 40% were strongly associated with fluid responsiveness. Accordingly, the patient will be given 10 ml/kg of bolus of 0.9% normal saline solution (NSS) each time when the IVCCI \> 40% is discovered and serial measurements will be done after each intravenous bolus is achieved until the IVCCI \< 40 % during our protocol. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
IVC Ultrasound-guided: IVC is identified in longitudinal section in the subcostal area of a patient using the curvilinear probe of standard ultrasound. The selected area of IVC diameter measurement is set at 2 centimeters distal to the confluence of hepatic vein by M-mode coupled by two-dimensional mode on frozen screen images using the Sonosite® X-porte.
Antibiotics: Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
Vasopressor: The threshold to the need of a vasopressor is set at mean arterial pressure below 65 mmHg if a patient's condition does not response to the fluid therapy.
|
Usual Care
n=101 Participants
Patients will be promptly and empirically treated by 30 ml/kg loading of NSS in this treatment arm. After the NSS bolus, treatment with either the additional intravenous fluid or a vasopressor is given depended on physicians' discretion during the 6-hour study period. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
|
|---|---|---|
|
30-day Mortality
|
20 Participants
|
19 Participants
|
SECONDARY outcome
Timeframe: 6 hours after treatmentPopulation: Data of 6-hour lactate was obtained among 100 patients (missing data in one patient) in the Usual care group and 100 patients (missing data in one patient) in the IVC Ultrasound-guided group .
The percentage change in blood lactate at 6 hour after initiation of treatment, calculated by \[(Initial blood lactate level at presentation - blood lactate level at 6 hours after treatment)/Initial blood lactate level at presentation\] x 100%. The higher positive value means the more relative reduction of blood lactate after treatment from that of initial presentation and indicates a better clinical outcome.
Outcome measures
| Measure |
IVC Ultrasound-guided
n=100 Participants
The treating physician will promptly assess the IVC diameter to obtain the collapsibility index (IVCCI) (or distensibility index, IVCDI) of an eligible patient. A previous study showed that IVCCI \> 40% were strongly associated with fluid responsiveness. Accordingly, the patient will be given 10 ml/kg of bolus of 0.9% normal saline solution (NSS) each time when the IVCCI \> 40% is discovered and serial measurements will be done after each intravenous bolus is achieved until the IVCCI \< 40 % during our protocol. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
IVC Ultrasound-guided: IVC is identified in longitudinal section in the subcostal area of a patient using the curvilinear probe of standard ultrasound. The selected area of IVC diameter measurement is set at 2 centimeters distal to the confluence of hepatic vein by M-mode coupled by two-dimensional mode on frozen screen images using the Sonosite® X-porte.
Antibiotics: Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
Vasopressor: The threshold to the need of a vasopressor is set at mean arterial pressure below 65 mmHg if a patient's condition does not response to the fluid therapy.
|
Usual Care
n=100 Participants
Patients will be promptly and empirically treated by 30 ml/kg loading of NSS in this treatment arm. After the NSS bolus, treatment with either the additional intravenous fluid or a vasopressor is given depended on physicians' discretion during the 6-hour study period. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
|
|---|---|---|
|
Percentage Change of 6-hour Lactate
|
39.2 percentage change
Interval 7.4 to 60.0
|
35.9 percentage change
Interval 16.3 to 65.5
|
SECONDARY outcome
Timeframe: 6 hours after treatmentCumulative amount of intravenous fluid (mL) during the first 6 hours after treatment.
Outcome measures
| Measure |
IVC Ultrasound-guided
n=101 Participants
The treating physician will promptly assess the IVC diameter to obtain the collapsibility index (IVCCI) (or distensibility index, IVCDI) of an eligible patient. A previous study showed that IVCCI \> 40% were strongly associated with fluid responsiveness. Accordingly, the patient will be given 10 ml/kg of bolus of 0.9% normal saline solution (NSS) each time when the IVCCI \> 40% is discovered and serial measurements will be done after each intravenous bolus is achieved until the IVCCI \< 40 % during our protocol. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
IVC Ultrasound-guided: IVC is identified in longitudinal section in the subcostal area of a patient using the curvilinear probe of standard ultrasound. The selected area of IVC diameter measurement is set at 2 centimeters distal to the confluence of hepatic vein by M-mode coupled by two-dimensional mode on frozen screen images using the Sonosite® X-porte.
Antibiotics: Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
Vasopressor: The threshold to the need of a vasopressor is set at mean arterial pressure below 65 mmHg if a patient's condition does not response to the fluid therapy.
|
Usual Care
n=101 Participants
Patients will be promptly and empirically treated by 30 ml/kg loading of NSS in this treatment arm. After the NSS bolus, treatment with either the additional intravenous fluid or a vasopressor is given depended on physicians' discretion during the 6-hour study period. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
|
|---|---|---|
|
6-hour Cumulative Amount of Intravenous Fluid (mL)
|
1900 mL
Interval 1500.0 to 2570.0
|
2600 mL
Interval 2300.0 to 3220.0
|
SECONDARY outcome
Timeframe: 72 hours after treatmentPopulation: Data of 72-hour cumulative amount of intravenous fluid was available among 83 patients (missing data in 18 patients; 6 discharge within 72 hours, 5 transfer out, 4 missing records and 3 death within 72 hours) in the Usual care group and 79 patients (missing data in 22 patients, 10 discharge within 72 hours, 4 transfer out, 3 missing records, 5 death within 72 hours) in the IVC Ultrasound-guided group .
Cumulative amount of intravenous fluid (mL) during the first 72 hours after treatment.
Outcome measures
| Measure |
IVC Ultrasound-guided
n=79 Participants
The treating physician will promptly assess the IVC diameter to obtain the collapsibility index (IVCCI) (or distensibility index, IVCDI) of an eligible patient. A previous study showed that IVCCI \> 40% were strongly associated with fluid responsiveness. Accordingly, the patient will be given 10 ml/kg of bolus of 0.9% normal saline solution (NSS) each time when the IVCCI \> 40% is discovered and serial measurements will be done after each intravenous bolus is achieved until the IVCCI \< 40 % during our protocol. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
IVC Ultrasound-guided: IVC is identified in longitudinal section in the subcostal area of a patient using the curvilinear probe of standard ultrasound. The selected area of IVC diameter measurement is set at 2 centimeters distal to the confluence of hepatic vein by M-mode coupled by two-dimensional mode on frozen screen images using the Sonosite® X-porte.
Antibiotics: Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
Vasopressor: The threshold to the need of a vasopressor is set at mean arterial pressure below 65 mmHg if a patient's condition does not response to the fluid therapy.
|
Usual Care
n=83 Participants
Patients will be promptly and empirically treated by 30 ml/kg loading of NSS in this treatment arm. After the NSS bolus, treatment with either the additional intravenous fluid or a vasopressor is given depended on physicians' discretion during the 6-hour study period. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
|
|---|---|---|
|
72-hour Cumulative Amount of Intravenous Fluid (mL) After Treatment
|
7,300 mL
Interval 5040.0 to 9200.0
|
7,702 mL
Interval 5900.0 to 11275.0
|
SECONDARY outcome
Timeframe: 72 hours after treatmentPopulation: Data of 72-hour cumulative amount of intravenous fluid was available among 86 patients (missing data in 15 patients; 6 discharge within 72 hours, 5 transfer out, 1 lack of sufficient information and 3 death within 72 hours) in the Usual care group and 78 patients (missing data in 23 patients, 10 discharge within 72 hours, 4 transfer out, 4 lack of sufficient information, 5 death within 72 hours ) in the IVC Ultrasound-guided group .
The change in Sequential Organ Failure Assessment (SOFA) score between the score at initial presentation and 72 hours after treatment, determined by SOFA score at presentation minus the SOFA score at 72 hours after treatment. The possible minimum and maximum value of the change in SOFA score are -24 and +24, respectively. The higher value means the more relative reduction in SOFA score at 72 hours and indicates a better clinical outcome.
Outcome measures
| Measure |
IVC Ultrasound-guided
n=78 Participants
The treating physician will promptly assess the IVC diameter to obtain the collapsibility index (IVCCI) (or distensibility index, IVCDI) of an eligible patient. A previous study showed that IVCCI \> 40% were strongly associated with fluid responsiveness. Accordingly, the patient will be given 10 ml/kg of bolus of 0.9% normal saline solution (NSS) each time when the IVCCI \> 40% is discovered and serial measurements will be done after each intravenous bolus is achieved until the IVCCI \< 40 % during our protocol. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
IVC Ultrasound-guided: IVC is identified in longitudinal section in the subcostal area of a patient using the curvilinear probe of standard ultrasound. The selected area of IVC diameter measurement is set at 2 centimeters distal to the confluence of hepatic vein by M-mode coupled by two-dimensional mode on frozen screen images using the Sonosite® X-porte.
Antibiotics: Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
Vasopressor: The threshold to the need of a vasopressor is set at mean arterial pressure below 65 mmHg if a patient's condition does not response to the fluid therapy.
|
Usual Care
n=86 Participants
Patients will be promptly and empirically treated by 30 ml/kg loading of NSS in this treatment arm. After the NSS bolus, treatment with either the additional intravenous fluid or a vasopressor is given depended on physicians' discretion during the 6-hour study period. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
|
|---|---|---|
|
Change in Sequential Organ Failure Assessment (SOFA) Score in 72 Hours After Treatment
|
1 Score on a scale
Interval -1.0 to 3.0
|
1 Score on a scale
Interval -1.0 to 2.0
|
Adverse Events
IVC Ultrasound-guided
Serious events: 31 serious events
Other events: 4 other events
Deaths: 20 deaths
Usual Care
Serious events: 35 serious events
Other events: 2 other events
Deaths: 19 deaths
Serious adverse events
| Measure |
IVC Ultrasound-guided
n=101 participants at risk
The treating physician will promptly assess the IVC diameter to obtain the collapsibility index (IVCCI) (or distensibility index, IVCDI) of an eligible patient. A previous study showed that IVCCI \> 40% were strongly associated with fluid responsiveness. Accordingly, the patient will be given 10 ml/kg of bolus of 0.9% normal saline solution (NSS) each time when the IVCCI \> 40% is discovered and serial measurements will be done after each intravenous bolus is achieved until the IVCCI \< 40 % during our protocol. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
IVC Ultrasound-guided: IVC is identified in longitudinal section in the subcostal area of a patient using the curvilinear probe of standard ultrasound. The selected area of IVC diameter measurement is set at 2 centimeters distal to the confluence of hepatic vein by M-mode coupled by two-dimensional mode on frozen screen images using the Sonosite® X-porte.
Antibiotics: Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
Vasopressor: The threshold to the need of a vasopressor is set at mean arterial pressure below 65 mmHg if a patient's condition does not response to the fluid therapy.
|
Usual Care
n=101 participants at risk
Patients will be promptly and empirically treated by 30 ml/kg loading of NSS in this treatment arm. After the NSS bolus, treatment with either the additional intravenous fluid or a vasopressor is given depended on physicians' discretion during the 6-hour study period. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
|
|---|---|---|
|
Renal and urinary disorders
Renal replacement therapy
|
7.9%
8/101 • Number of events 8 • 30 days
|
5.0%
5/101 • Number of events 5 • 30 days
|
|
Respiratory, thoracic and mediastinal disorders
Mechanical ventilator
|
22.8%
23/101 • Number of events 23 • 30 days
|
29.7%
30/101 • Number of events 30 • 30 days
|
Other adverse events
| Measure |
IVC Ultrasound-guided
n=101 participants at risk
The treating physician will promptly assess the IVC diameter to obtain the collapsibility index (IVCCI) (or distensibility index, IVCDI) of an eligible patient. A previous study showed that IVCCI \> 40% were strongly associated with fluid responsiveness. Accordingly, the patient will be given 10 ml/kg of bolus of 0.9% normal saline solution (NSS) each time when the IVCCI \> 40% is discovered and serial measurements will be done after each intravenous bolus is achieved until the IVCCI \< 40 % during our protocol. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
IVC Ultrasound-guided: IVC is identified in longitudinal section in the subcostal area of a patient using the curvilinear probe of standard ultrasound. The selected area of IVC diameter measurement is set at 2 centimeters distal to the confluence of hepatic vein by M-mode coupled by two-dimensional mode on frozen screen images using the Sonosite® X-porte.
Antibiotics: Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
Vasopressor: The threshold to the need of a vasopressor is set at mean arterial pressure below 65 mmHg if a patient's condition does not response to the fluid therapy.
|
Usual Care
n=101 participants at risk
Patients will be promptly and empirically treated by 30 ml/kg loading of NSS in this treatment arm. After the NSS bolus, treatment with either the additional intravenous fluid or a vasopressor is given depended on physicians' discretion during the 6-hour study period. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
|
|---|---|---|
|
Renal and urinary disorders
Acute kidney injury
|
4.0%
4/101 • Number of events 101 • 30 days
|
2.0%
2/101 • Number of events 101 • 30 days
|
Additional Information
Dr. Khrongwong Musikatavorn
Department of Emergency Medicine, Faculty of Medicine, Chulalongkorn University
Phone: +6626494000
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place