Trial Outcomes & Findings for Citrulline in Severe Sepsis (NCT NCT01474863)
NCT ID: NCT01474863
Last Updated: 2017-06-05
Results Overview
Worst Value of Index measuring blood pressure hourly through study infusion (day 4). Vasopressor index is mean arterial blood pressure divided by catecholamine index (the catecholamine index is a dimensionless variable calculated as (dopamine dose × 1) + (dobutamine dose × 1) + (adrenaline dose × 10) + (noradrenaline × 100) + (phenylephrine dose × 100), where all doses are expressed in ug/kg/min). (Higher is better)
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
72 participants
Primary outcome timeframe
day 4
Results posted on
2017-06-05
Participant Flow
Participant milestones
| Measure |
Low Dose Citrulline
Low Dose Citrulline
Low Dose Citrulline: Initial intravenous bolus of 10mg/kg (to a maximum of 1500mg) L-citrulline over 10 minutes. Immediately after the initial bolus, a continuous intravenous infusion of L-citrulline at 4.5mg/kg (max 350mg) per hour will be administered through a dedicated intravenous line or port of a multilumen catheter for 4 days.
|
Placebo
Placebo IV infusion
Placebo: D5W IV fluids at isovolumetric rate (about 15ml/hr)
|
High Dose Citrulline
High Dose Citrulline
High Dose Citrulline: Initial intravenous bolus of 20mg/kg (to a maximum of 1500mg) L-citrulline over 10 minutes. Immediately after the initial bolus, a continuous intravenous infusion of L-citrulline at 9mg/kg (max 700mg) per hour will be administered through a dedicated intravenous line or port of a multilumen catheter for 4 days
|
|---|---|---|---|
|
Overall Study
STARTED
|
26
|
22
|
24
|
|
Overall Study
COMPLETED
|
26
|
22
|
24
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Citrulline in Severe Sepsis
Baseline characteristics by cohort
| Measure |
Low Dose Citrulline
n=26 Participants
Low Dose Citrulline
Low Dose Citrulline: Initial intravenous bolus of 10mg/kg (to a maximum of 1500mg) L-citrulline over 10 minutes. Immediately after the initial bolus, a continuous intravenous infusion of L-citrulline at 4.5mg/kg (max 350mg) per hour will be administered through a dedicated intravenous line or port of a multilumen catheter for 4 days.
|
Placebo
n=22 Participants
Placebo IV infusion
Placebo: D5W IV fluids at isovolumetric rate (about 15ml/hr)
|
High Dose Citrulline
n=24 Participants
High Dose Citrulline
High Dose Citrulline: Initial intravenous bolus of 20mg/kg (to a maximum of 1500mg) L-citrulline over 10 minutes. Immediately after the initial bolus, a continuous intravenous infusion of L-citrulline at 9mg/kg (max 700mg) per hour will be administered through a dedicated intravenous line or port of a multilumen catheter for 4 days
|
Total
n=72 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
54.4 years
STANDARD_DEVIATION 17.1 • n=93 Participants
|
56.2 years
STANDARD_DEVIATION 16.8 • n=4 Participants
|
51.8 years
STANDARD_DEVIATION 16.6 • n=27 Participants
|
54.1 years
STANDARD_DEVIATION 16.8 • n=483 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=93 Participants
|
8 Participants
n=4 Participants
|
12 Participants
n=27 Participants
|
30 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=93 Participants
|
14 Participants
n=4 Participants
|
12 Participants
n=27 Participants
|
42 Participants
n=483 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
9 Participants
n=483 Participants
|
|
Race (NIH/OMB)
White
|
23 Participants
n=93 Participants
|
18 Participants
n=4 Participants
|
22 Participants
n=27 Participants
|
63 Participants
n=483 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Region of Enrollment
United States
|
26 participants
n=93 Participants
|
22 participants
n=4 Participants
|
24 participants
n=27 Participants
|
72 participants
n=483 Participants
|
PRIMARY outcome
Timeframe: day 4Worst Value of Index measuring blood pressure hourly through study infusion (day 4). Vasopressor index is mean arterial blood pressure divided by catecholamine index (the catecholamine index is a dimensionless variable calculated as (dopamine dose × 1) + (dobutamine dose × 1) + (adrenaline dose × 10) + (noradrenaline × 100) + (phenylephrine dose × 100), where all doses are expressed in ug/kg/min). (Higher is better)
Outcome measures
| Measure |
Low Dose Citrulline
n=26 Participants
Low Dose Citrulline
Low Dose Citrulline: Initial intravenous bolus of 10mg/kg (to a maximum of 1500mg) L-citrulline over 10 minutes. Immediately after the initial bolus, a continuous intravenous infusion of L-citrulline at 4.5mg/kg (max 350mg) per hour will be administered through a dedicated intravenous line or port of a multilumen catheter for 4 days.
|
Placebo
n=22 Participants
Placebo IV infusion
Placebo: D5W IV fluids at isovolumetric rate (about 15ml/hr)
|
High Dose Citrulline
n=24 Participants
High Dose Citrulline
High Dose Citrulline: Initial intravenous bolus of 20mg/kg (to a maximum of 1500mg) L-citrulline over 10 minutes. Immediately after the initial bolus, a continuous intravenous infusion of L-citrulline at 9mg/kg (max 700mg) per hour will be administered through a dedicated intravenous line or port of a multilumen catheter for 4 days
|
|---|---|---|---|
|
Vasopressor Dependency Index
|
50.0 mmHg/catecholamine index
Standard Deviation 28.8
|
44.4 mmHg/catecholamine index
Standard Deviation 30.9
|
49.0 mmHg/catecholamine index
Standard Deviation 27.4
|
Adverse Events
Low Dose Citrulline
Serious events: 5 serious events
Other events: 0 other events
Deaths: 5 deaths
Placebo
Serious events: 5 serious events
Other events: 0 other events
Deaths: 5 deaths
High Dose Citrulline
Serious events: 3 serious events
Other events: 0 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Low Dose Citrulline
n=26 participants at risk
Low Dose Citrulline
Low Dose Citrulline: Initial intravenous bolus of 10mg/kg (to a maximum of 1500mg) L-citrulline over 10 minutes. Immediately after the initial bolus, a continuous intravenous infusion of L-citrulline at 4.5mg/kg (max 350mg) per hour will be administered through a dedicated intravenous line or port of a multilumen catheter for 4 days.
|
Placebo
n=22 participants at risk
Placebo IV infusion
Placebo: D5W IV fluids at isovolumetric rate (about 15ml/hr)
|
High Dose Citrulline
n=24 participants at risk
High Dose Citrulline
High Dose Citrulline: Initial intravenous bolus of 20mg/kg (to a maximum of 1500mg) L-citrulline over 10 minutes. Immediately after the initial bolus, a continuous intravenous infusion of L-citrulline at 9mg/kg (max 700mg) per hour will be administered through a dedicated intravenous line or port of a multilumen catheter for 4 days
|
|---|---|---|---|
|
Cardiac disorders
Death
|
19.2%
5/26 • Number of events 5
|
22.7%
5/22 • Number of events 5
|
12.5%
3/24 • Number of events 3
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place