Trial Outcomes & Findings for Thiamine as a Metabolic Resuscitator After Cardiac Arrest (NCT NCT03450707)
NCT ID: NCT03450707
Last Updated: 2023-08-24
Results Overview
Blood Lactate Over Time
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
93 participants
Primary outcome timeframe
24 hours
Results posted on
2023-08-24
Participant Flow
Participant milestones
| Measure |
Thiamine
Patients randomized to the thiamine arm will receive thiamine 500mg in 100mL of normal saline intravenously every 12 hours for 5 doses. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Thiamine 500 mg IV: Thiamine hydrochloride (vitamin B1) 500mg IV will be given every 12 hours for 5 doses in the experimental arm.
|
Placebo
Patients randomized to placebo will receive 100mL normal saline intravenously every 12 hours for 5 doses. All other aspects of the protocol will be the same as in the experimental arm. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Placebo: 100mL of intravenous normal saline will be given every 12hours for 5 doses in the placebo arm
|
|---|---|---|
|
Overall Study
STARTED
|
47
|
46
|
|
Overall Study
COMPLETED
|
40
|
36
|
|
Overall Study
NOT COMPLETED
|
7
|
10
|
Reasons for withdrawal
| Measure |
Thiamine
Patients randomized to the thiamine arm will receive thiamine 500mg in 100mL of normal saline intravenously every 12 hours for 5 doses. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Thiamine 500 mg IV: Thiamine hydrochloride (vitamin B1) 500mg IV will be given every 12 hours for 5 doses in the experimental arm.
|
Placebo
Patients randomized to placebo will receive 100mL normal saline intravenously every 12 hours for 5 doses. All other aspects of the protocol will be the same as in the experimental arm. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Placebo: 100mL of intravenous normal saline will be given every 12hours for 5 doses in the placebo arm
|
|---|---|---|
|
Overall Study
Outside enrollment window
|
4
|
1
|
|
Overall Study
Death
|
1
|
0
|
|
Overall Study
Indication for thiamine
|
1
|
1
|
|
Overall Study
Evidence of traumatic brain injury
|
1
|
0
|
|
Overall Study
Following commands
|
0
|
3
|
|
Overall Study
Lactate < 3.5
|
0
|
2
|
|
Overall Study
Rearrest with ECMO
|
0
|
1
|
|
Overall Study
Indication for thiamine + head CT results
|
0
|
1
|
|
Overall Study
Family/patient goals of care
|
0
|
1
|
Baseline Characteristics
Thiamine as a Metabolic Resuscitator After Cardiac Arrest
Baseline characteristics by cohort
| Measure |
Thiamine
n=40 Participants
Patients randomized to the thiamine arm will receive thiamine 500mg in 100mL of normal saline intravenously every 12 hours for 5 doses. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Thiamine 500 mg IV: Thiamine hydrochloride (vitamin B1) 500mg IV will be given every 12 hours for 5 doses in the experimental arm.
|
Placebo
n=36 Participants
Patients randomized to placebo will receive 100mL normal saline intravenously every 12 hours for 5 doses. All other aspects of the protocol will be the same as in the experimental arm. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Placebo: 100mL of intravenous normal saline will be given every 12hours for 5 doses in the placebo arm
|
Total
n=76 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
68.5 years
n=5 Participants
|
65.5 years
n=7 Participants
|
66.5 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
25 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
14 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
24 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · White
|
10 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · Black
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · Asian
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · Other
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · Unknown
|
21 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
|
Initial Rhythm
Pulseless electrical activity
|
15 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Initial Rhythm
Asystole
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Initial Rhythm
Ventricular Fibrillation
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Initial Rhythm
Pulseless Ventricular Tachycardia
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Initial Rhythm
Unknown Shockable
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Initial Rhythm
Unknown Non-Shockable
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 24 hoursPopulation: Seventeen patients (six in the placebo arm and eleven in the thiamine arm) missing 24-hour lactate as they had expired by this timepoint.
Blood Lactate Over Time
Outcome measures
| Measure |
Thiamine
n=29 Participants
Patients randomized to the thiamine arm will receive thiamine 500mg in 100mL of normal saline intravenously every 12 hours for 5 doses. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Thiamine 500 mg IV: Thiamine hydrochloride (vitamin B1) 500mg IV will be given every 12 hours for 5 doses in the experimental arm.
|
Placebo
n=30 Participants
Patients randomized to placebo will receive 100mL normal saline intravenously every 12 hours for 5 doses. All other aspects of the protocol will be the same as in the experimental arm. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Placebo: 100mL of intravenous normal saline will be given every 12hours for 5 doses in the placebo arm
|
|---|---|---|
|
Lactate
|
1.8 mmol/L
Interval 1.2 to 2.4
|
2.2 mmol/L
Interval 1.4 to 2.5
|
SECONDARY outcome
Timeframe: 48 hoursPopulation: Only 12 patients in the thiamine group and 18 patients in the placebo group had atleast 60 minutes of metabolic data in the first 48 hours after study drug administration
Global Oxygen Consumption over Time
Outcome measures
| Measure |
Thiamine
n=12 Participants
Patients randomized to the thiamine arm will receive thiamine 500mg in 100mL of normal saline intravenously every 12 hours for 5 doses. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Thiamine 500 mg IV: Thiamine hydrochloride (vitamin B1) 500mg IV will be given every 12 hours for 5 doses in the experimental arm.
|
Placebo
n=18 Participants
Patients randomized to placebo will receive 100mL normal saline intravenously every 12 hours for 5 doses. All other aspects of the protocol will be the same as in the experimental arm. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Placebo: 100mL of intravenous normal saline will be given every 12hours for 5 doses in the placebo arm
|
|---|---|---|
|
Global Oxygen Consumption
|
3.52 Area under the Curve VO2 (mL/kg/min)
Standard Deviation 1.50
|
3.93 Area under the Curve VO2 (mL/kg/min)
Standard Deviation 1.05
|
SECONDARY outcome
Timeframe: 72 hoursPopulation: Thirty-two patients (thirteen in the placebo arm and nineteen in the thiamine arm) missing 72-hour lactate as they had expired prior to the 72-hour timepoint. In addition, two more patients in the placebo arm alive at 72 hours were missing 72-hour lactate due to health care provider request/patient refusal. No imputation was done for this secondary outcome.
Absolute Blood Level of Lactate
Outcome measures
| Measure |
Thiamine
n=21 Participants
Patients randomized to the thiamine arm will receive thiamine 500mg in 100mL of normal saline intravenously every 12 hours for 5 doses. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Thiamine 500 mg IV: Thiamine hydrochloride (vitamin B1) 500mg IV will be given every 12 hours for 5 doses in the experimental arm.
|
Placebo
n=21 Participants
Patients randomized to placebo will receive 100mL normal saline intravenously every 12 hours for 5 doses. All other aspects of the protocol will be the same as in the experimental arm. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Placebo: 100mL of intravenous normal saline will be given every 12hours for 5 doses in the placebo arm
|
|---|---|---|
|
Lactate
|
1.3 mmol/L
Interval 0.9 to 1.6
|
1.3 mmol/L
Interval 0.9 to 1.5
|
SECONDARY outcome
Timeframe: 72 hoursPopulation: Only 20 patients from the thiamine group and 15 patients from the placebo group were alive and had PDH specific activity available at 72 hours.
Absolute PDH specific activity value
Outcome measures
| Measure |
Thiamine
n=20 Participants
Patients randomized to the thiamine arm will receive thiamine 500mg in 100mL of normal saline intravenously every 12 hours for 5 doses. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Thiamine 500 mg IV: Thiamine hydrochloride (vitamin B1) 500mg IV will be given every 12 hours for 5 doses in the experimental arm.
|
Placebo
n=15 Participants
Patients randomized to placebo will receive 100mL normal saline intravenously every 12 hours for 5 doses. All other aspects of the protocol will be the same as in the experimental arm. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Placebo: 100mL of intravenous normal saline will be given every 12hours for 5 doses in the placebo arm
|
|---|---|---|
|
Pyruvate Dehydrogenase (PDH) Specific Activity
|
1.55 Ratio [PDH activity/ln(PDH quantity)]
Interval 0.88 to 2.11
|
0.97 Ratio [PDH activity/ln(PDH quantity)]
Interval 0.78 to 1.6
|
SECONDARY outcome
Timeframe: 72 hoursPopulation: Only 20 patients from the thiamine group and 16 patients from the placebo group were alive and had PDH activity available at 72 hours.
Absolute PDH Activity Value
Outcome measures
| Measure |
Thiamine
n=20 Participants
Patients randomized to the thiamine arm will receive thiamine 500mg in 100mL of normal saline intravenously every 12 hours for 5 doses. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Thiamine 500 mg IV: Thiamine hydrochloride (vitamin B1) 500mg IV will be given every 12 hours for 5 doses in the experimental arm.
|
Placebo
n=16 Participants
Patients randomized to placebo will receive 100mL normal saline intravenously every 12 hours for 5 doses. All other aspects of the protocol will be the same as in the experimental arm. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Placebo: 100mL of intravenous normal saline will be given every 12hours for 5 doses in the placebo arm
|
|---|---|---|
|
Pyruvate Dehydrogenase (PDH) Activity
|
8.63 mini OD unit/min/mg protein
Interval 4.93 to 12.9
|
5.65 mini OD unit/min/mg protein
Interval 4.77 to 9.38
|
SECONDARY outcome
Timeframe: 72 hoursPopulation: Only 20 patients from the thiamine group and 15 patients from the placebo group were alive and had PDH quantity available at 72 hours.
Absolute PDH Quantity. Please note that the measurement of Absolute PDH Quantity is done using a relative quantity assay, and that PDH is an enzyme and not a stable protein; therefore the units of measure cannot be provided in "mg" and are instead listed in "mini OD unit/min/mg protein".
Outcome measures
| Measure |
Thiamine
n=20 Participants
Patients randomized to the thiamine arm will receive thiamine 500mg in 100mL of normal saline intravenously every 12 hours for 5 doses. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Thiamine 500 mg IV: Thiamine hydrochloride (vitamin B1) 500mg IV will be given every 12 hours for 5 doses in the experimental arm.
|
Placebo
n=15 Participants
Patients randomized to placebo will receive 100mL normal saline intravenously every 12 hours for 5 doses. All other aspects of the protocol will be the same as in the experimental arm. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Placebo: 100mL of intravenous normal saline will be given every 12hours for 5 doses in the placebo arm
|
|---|---|---|
|
Pyruvate Dehydrogenase (PDH) Quantity
|
588.05 mini OD unit/min/mg protein
Interval 291.31 to 1080.94
|
695.55 mini OD unit/min/mg protein
Interval 437.94 to 999.09
|
SECONDARY outcome
Timeframe: will be assessed at hospital discharge and up to 30 and 90 days.Population: For 90-day mortality, two patients from the placebo arm were not reachable for follow-up and thus are missing this information.
Mortality in the study assessed at three timepoints.
Outcome measures
| Measure |
Thiamine
n=40 Participants
Patients randomized to the thiamine arm will receive thiamine 500mg in 100mL of normal saline intravenously every 12 hours for 5 doses. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Thiamine 500 mg IV: Thiamine hydrochloride (vitamin B1) 500mg IV will be given every 12 hours for 5 doses in the experimental arm.
|
Placebo
n=36 Participants
Patients randomized to placebo will receive 100mL normal saline intravenously every 12 hours for 5 doses. All other aspects of the protocol will be the same as in the experimental arm. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Placebo: 100mL of intravenous normal saline will be given every 12hours for 5 doses in the placebo arm
|
|---|---|---|
|
Mortality
90-day mortality
|
30 Participants
|
24 Participants
|
|
Mortality
Discharge mortality
|
30 Participants
|
23 Participants
|
|
Mortality
30-day mortality
|
30 Participants
|
24 Participants
|
SECONDARY outcome
Timeframe: will be assessed up to 30 and 90 daysPopulation: Two patients, both from placebo arm, did not have 30 day CPC scores available. Four patients, all from the placebo arm, did not have 90 day CPC scores available.
Count/Proportion of Patients Scoring a Favorable CPC, defined as a score of 1 or 2. Cerebral performance category scores range from 1-5. Lower scores mean better outcomes.
Outcome measures
| Measure |
Thiamine
n=40 Participants
Patients randomized to the thiamine arm will receive thiamine 500mg in 100mL of normal saline intravenously every 12 hours for 5 doses. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Thiamine 500 mg IV: Thiamine hydrochloride (vitamin B1) 500mg IV will be given every 12 hours for 5 doses in the experimental arm.
|
Placebo
n=36 Participants
Patients randomized to placebo will receive 100mL normal saline intravenously every 12 hours for 5 doses. All other aspects of the protocol will be the same as in the experimental arm. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Placebo: 100mL of intravenous normal saline will be given every 12hours for 5 doses in the placebo arm
|
|---|---|---|
|
Favorable Cerebral Performance Category (CPC)
Favorable Discharge CPC (1-2)
|
8 Participants
|
10 Participants
|
|
Favorable Cerebral Performance Category (CPC)
Favorable 30-day CPC (1-2)
|
9 Participants
|
9 Participants
|
|
Favorable Cerebral Performance Category (CPC)
Favorable 90-day CPC (1-2)
|
9 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: over 72 hoursPopulation: 13 patients in the placebo arm and 19 patients in the thiamine arm missing 72-hour SOFA scores as they had expired by this timepoint. 3 additional patients in the placebo arm were alive at 72-hours but are still missing 72-hour SOFA scores because one or more component scores required to calculate the SOFA scores were missing.
SOFA score over time. SOFA score: Sequential Organ Failure Assessment Score, ranges from 0-24, higher scores mean worse outcomes.
Outcome measures
| Measure |
Thiamine
n=21 Participants
Patients randomized to the thiamine arm will receive thiamine 500mg in 100mL of normal saline intravenously every 12 hours for 5 doses. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Thiamine 500 mg IV: Thiamine hydrochloride (vitamin B1) 500mg IV will be given every 12 hours for 5 doses in the experimental arm.
|
Placebo
n=20 Participants
Patients randomized to placebo will receive 100mL normal saline intravenously every 12 hours for 5 doses. All other aspects of the protocol will be the same as in the experimental arm. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Placebo: 100mL of intravenous normal saline will be given every 12hours for 5 doses in the placebo arm
|
|---|---|---|
|
Sequential Organ Failure Assessment (SOFA) Score
|
9 score on a scale
Interval 7.0 to 12.0
|
6 score on a scale
Interval 4.0 to 9.0
|
SECONDARY outcome
Timeframe: First 7 days following ArrestPopulation: Three patients from the placebo arm and one from the thiamine arm were excluded from the renal failure analyses due to pre-arrest end-stage renal disease requiring dialyses.
Determined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria for Stage 3 acute kidney injury/kidney failure.
Outcome measures
| Measure |
Thiamine
n=39 Participants
Patients randomized to the thiamine arm will receive thiamine 500mg in 100mL of normal saline intravenously every 12 hours for 5 doses. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Thiamine 500 mg IV: Thiamine hydrochloride (vitamin B1) 500mg IV will be given every 12 hours for 5 doses in the experimental arm.
|
Placebo
n=33 Participants
Patients randomized to placebo will receive 100mL normal saline intravenously every 12 hours for 5 doses. All other aspects of the protocol will be the same as in the experimental arm. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Placebo: 100mL of intravenous normal saline will be given every 12hours for 5 doses in the placebo arm
|
|---|---|---|
|
Acute Renal Failure
|
9 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: 0 hours and 24 hours.Population: Two patients from the thiamine group had a thiamine value \>1200 and were excluded.
Absolute Cellular Oxygen Consumption Rate: We use two measures to capture Oxygen Consumption Rate; the basal respiration and the maximal respiration.
Outcome measures
| Measure |
Thiamine
n=38 Participants
Patients randomized to the thiamine arm will receive thiamine 500mg in 100mL of normal saline intravenously every 12 hours for 5 doses. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Thiamine 500 mg IV: Thiamine hydrochloride (vitamin B1) 500mg IV will be given every 12 hours for 5 doses in the experimental arm.
|
Placebo
n=36 Participants
Patients randomized to placebo will receive 100mL normal saline intravenously every 12 hours for 5 doses. All other aspects of the protocol will be the same as in the experimental arm. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Placebo: 100mL of intravenous normal saline will be given every 12hours for 5 doses in the placebo arm
|
|---|---|---|
|
Cellular Oxygen Consumption
Basal respiration-0 hours
|
5.6 pmol/min/mg protein
Interval 4.3 to 7.8
|
4.8 pmol/min/mg protein
Interval 3.2 to 7.9
|
|
Cellular Oxygen Consumption
Maximal respiration-0 hours
|
19.3 pmol/min/mg protein
Interval 7.9 to 36.1
|
11.9 pmol/min/mg protein
Interval 6.8 to 30.3
|
|
Cellular Oxygen Consumption
Basal respiration-24 hours
|
5.5 pmol/min/mg protein
Interval 2.6 to 6.3
|
4.7 pmol/min/mg protein
Interval 3.4 to 9.3
|
|
Cellular Oxygen Consumption
Maximal respiration-24 hours
|
14.7 pmol/min/mg protein
Interval 10.4 to 25.1
|
16.1 pmol/min/mg protein
Interval 11.5 to 34.3
|
SECONDARY outcome
Timeframe: 72 hoursPopulation: Thirty-two patients (thirteen in the placebo arm and nineteen in the thiamine arm) missing 72-hour creatinine as they had expired prior to the 72-hour timepoint.
Creatinine over Time
Outcome measures
| Measure |
Thiamine
n=21 Participants
Patients randomized to the thiamine arm will receive thiamine 500mg in 100mL of normal saline intravenously every 12 hours for 5 doses. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Thiamine 500 mg IV: Thiamine hydrochloride (vitamin B1) 500mg IV will be given every 12 hours for 5 doses in the experimental arm.
|
Placebo
n=23 Participants
Patients randomized to placebo will receive 100mL normal saline intravenously every 12 hours for 5 doses. All other aspects of the protocol will be the same as in the experimental arm. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.
Placebo: 100mL of intravenous normal saline will be given every 12hours for 5 doses in the placebo arm
|
|---|---|---|
|
Creatinine
|
1.9 mg/dL
Interval 0.9 to 2.8
|
1.1 mg/dL
Interval 0.8 to 1.9
|
SECONDARY outcome
Timeframe: various time points over 7 daysPopulation: Biomarker assays not run in the laboratory at this time
S100 and NSE levels at various time points
Outcome measures
Outcome data not reported
Adverse Events
Thiamine
Serious events: 0 serious events
Other events: 0 other events
Deaths: 30 deaths
Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 24 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place