Septic Shock
Conditions
Keywords
Septic Shock, Sepsis
Brief summary
The major goal of this project is to determine whether the use of thiamine in patients with septic shock will result in attenuation of lactic acidosis and a more rapid reversal of shock.
Interventions
DRUGD5W
Dextrose 5%
DRUGThiamine
Thiamine 200mg in 50ml D5W
Sponsors
National Institutes of Health (NIH)
National Center for Complementary and Integrative Health (NCCIH)
Beth Israel Deaconess Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Greater than 18 years old * Suspected or confirmed source of infection * Hypotension (systolic pressure \<90 mmHg) after a minimum 2 liter fluid bolus followed by vasopressor-dependence. * Lactic Acidosis \> 3 mmol/dl
Exclusion criteria
* Competing cause of lactic acidosis including: seizures within 3 hours of enrollment, use of linazolid metformin or anti-retrovirals at the time of enrollment, carbon monoxide or cyanide poisoning, highly suspected or known ischemic bowel, and known mitochondrial disorders * Liver dysfunction specifically defined as AST or ALT elevation greater than 240 * Current Thiamine supplements or usage * Competing indication for thiamine administration * Cardiac Arrest * DNR/DNI or comfort care status (DNR status in an intubated patient receiving full care is eligible)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Lactate Level 24 Hours After the First Study Medication Dose | 24 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Shock Reversal | Hospital stay, average 2 weeks | Shock reversal was defined as \> 24 hours off all vasopressors |
| APACHE II Score at 24 Hours | 24 hours | APACHE II (Acute Physiology and Chronic Health Evaluation II) is a severity-of-disease classification system; an integer score from 0 to 71 is computed based on several measurements; higher scores correspond to more severe disease and a higher risk of death |
Other
| Measure | Time frame | Description |
|---|---|---|
| Lactate Level at 24 Hours in Patients With Baseline Thiamine Deficiency | 24 hours | Baseline thiamine deficiency was defined as a baseline thiamine level of ≤ 7 nmol/L |
| Number of Participants Dying Before Hospital Discharge in Patients With Baseline Thiamine Deficiency | Hospital stay, average 2 weeks | Baseline thiamine deficiency was defined as a baseline thiamine level of ≤ 7 nmol/L |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo 50 ml D5W D5W: Dextrose 5% | 45 |
| Thiamine 200mg Thiamine in 50ml D5W Thiamine: Thiamine 200mg in 50ml Dextrose 5% | 43 |
| Total | 88 |
Baseline characteristics
| Characteristic | Placebo | Thiamine | Total |
|---|---|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 17 | 70 years STANDARD_DEVIATION 14 | 67 years STANDARD_DEVIATION 16 |
| BMI | 29 kg/m^2 STANDARD_DEVIATION 7 | 29 kg/m^2 STANDARD_DEVIATION 9 | 29 kg/m^2 STANDARD_DEVIATION 8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 40 Participants | 36 Participants | 76 Participants |
| Region of Enrollment United States | 45 participants | 43 participants | 88 participants |
| Sex: Female, Male Female | 19 Participants | 17 Participants | 36 Participants |
| Sex: Female, Male Male | 26 Participants | 26 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 19 / 45 | 19 / 43 |
| other Total, other adverse events | 0 / 45 | 0 / 43 |
| serious Total, serious adverse events | 0 / 45 | 0 / 43 |
Outcome results
Primary
Lactate Level 24 Hours After the First Study Medication Dose
Time frame: 24 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Lactate Level 24 Hours After the First Study Medication Dose | 2.6 mmol/L |
| Thiamine | Lactate Level 24 Hours After the First Study Medication Dose | 2.5 mmol/L |
p-value: 0.4Wilcoxon (Mann-Whitney)
Secondary
APACHE II Score at 24 Hours
APACHE II (Acute Physiology and Chronic Health Evaluation II) is a severity-of-disease classification system; an integer score from 0 to 71 is computed based on several measurements; higher scores correspond to more severe disease and a higher risk of death
Time frame: 24 hours
Population: APACHE II was not available on 6 patients in each group at 24 hour mostly because of early death.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | APACHE II Score at 24 Hours | 26 units on a scale | Standard Deviation 10 |
| Thiamine | APACHE II Score at 24 Hours | 23 units on a scale | Standard Deviation 8 |
p-value: 0.15t-test, 2 sided
Secondary
Number of Participants With Shock Reversal
Shock reversal was defined as \> 24 hours off all vasopressors
Time frame: Hospital stay, average 2 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Shock Reversal | 32 Participants |
| Thiamine | Number of Participants With Shock Reversal | 32 Participants |
Comparison: Time to shock reversal was complicated by a high incidence of death prior to the event. To account for this we classified death as a competing risk event and used the estimated cumulative incidence function (CIF) to illustrate the comparison of CIFs between the two treatment groups using the Fine-Gray competing risk model. We tested the subdistribution hazards of these two CIF functions and obtained the estimated hazard ratio with 95% confidence intervals.p-value: 0.9795% CI: [0.61, 1.62]Regression, Cox
Other Pre-specified
Lactate Level at 24 Hours in Patients With Baseline Thiamine Deficiency
Baseline thiamine deficiency was defined as a baseline thiamine level of ≤ 7 nmol/L
Time frame: 24 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Lactate Level at 24 Hours in Patients With Baseline Thiamine Deficiency | 2.1 nmol/L |
| Thiamine | Lactate Level at 24 Hours in Patients With Baseline Thiamine Deficiency | 3.1 nmol/L |
p-value: 0.03Wilcoxon (Mann-Whitney)
Other Pre-specified
Number of Participants Dying Before Hospital Discharge in Patients With Baseline Thiamine Deficiency
Baseline thiamine deficiency was defined as a baseline thiamine level of ≤ 7 nmol/L
Time frame: Hospital stay, average 2 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Dying Before Hospital Discharge in Patients With Baseline Thiamine Deficiency | 2 Participants |
| Thiamine | Number of Participants Dying Before Hospital Discharge in Patients With Baseline Thiamine Deficiency | 6 Participants |
p-value: 0.1Chi-squared