Sepsis, Septic Shock
Conditions
Keywords
Sepsis, Septic Shock, Vitamin C, Thiamine
Brief summary
Investigators propose to investigate the use of IV vitamins B1 and C in a randomized, double-blinded, prospective trial to determine if these medications decrease mortality rates in patients with severe sepsis or septic shock.
Detailed description
Investigators propose to investigate the use of IV vitamins B1 and C in a randomized, double-blinded, prospective trial to determine if these medications decrease mortality rates in patients with severe sepsis or septic shock. Patients experiencing evidence-based diagnoses of sepsis and severe sepsis and septic shock will be randomized to the two study arms for care, and all other care left to decisions of intensive care teams.
Interventions
DRUGVitamin C
Patients will receive 1.5g of vitamin C in 100mL of 0.9% sodium chloride (normal saline) every six hours for four days or until discharge from the ICU, whichever happens first (seventeen dose maximum).
DRUGVitamin B1
Patients will also receive 200 mg of IV vitamin B1 every 12 hours in 50 mL of normal saline for four days or until ICU discharge (whichever happens first, nine dose maximum).
Sponsors
Trinity Health Of New England
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
All parties involved, except for pharmacy personnel will be blinded.
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
Patients must meet all inclusion criteria: 1. Between the ages of 18 and 90 years old 2. Have severe sepsis or septic shock. Severe sepsis and septic shock will be defined by the Surviving Sepsis 2012 guidelines. 3. Weight more than 30 kg 4. Full code
Exclusion criteria
1. Not diagnosed with severe sepsis or septic shock 2. Younger than 18 or older than 90 years old 3. With a history of nephrolithiasis 4. Who are pregnant 5. Weigh less than 30 kg 6. Not located in the ICU 7. Do not resuscitate (DNR) or do not intubate (DNI), no escalation of care, or comfort measures only (CMO) 8. Currently on dialysis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mortality Rates | From time of treatment to 30 days post hospital discharge, up to 87 days. | All-cause mortality from time of enrollment/treatment to 30 days post hospital discharge (up to 87 days) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospital Length of Stay | From admission to the hospital through hospital discharge, up to 57 days. | Total number of days patient is admitted to the hospital |
| Intensive Care Unit Length of Stay | From time of admission to the ICU through discharge from the ICU, up to 25 days | Total number of days patient is admitted to the ICU |
| Readmission Rate | 30 days after hospital discharge | Readmission to the hospital within 30 days after discharge |
| Ventilator Days | From admission to the ICU through discharge from the ICU, up to 25 days. | Number of days patient required ventilator |
| Hours on Vasopressors | From admission to the ICU through discharge from the ICU, up to 25 days. | Number of hours patient required vasopressors in norepinephrine equivalence. |
Countries
United States
Participant flow
Recruitment details
Patients admitted to the intensive care unit with a diagnosis of septic shock were identified by study team members, offered for recruitment, recruited and randomized upon arrival to the unit. This began September 14, 2018 and the final recruitment occurred on February 22, 2021.
Pre-assignment details
The only exclusions for for patients who opted out of the study following initial consent. No other run-in events occurred.
Participants by arm
| Arm | Count |
|---|---|
| Vitamins C and B1 Patients in this arm will receive 1.5g of vitamin C in 100mL of 0.9% sodium chloride (normal saline) every six hours for four days or until discharge from the ICU, whichever happens first (seventeen dose maximum). In addition, they will receive 200 mg IV vitamin B1 every 12 hours in 50 mL of normal saline for four days or until ICU discharge (whichever happens first, nine dose maximum).
Vitamin C: Patients will receive 1.5g of vitamin C in 100mL of 0.9% sodium chloride (normal saline) every six hours for four days or until discharge from the ICU, whichever happens first (seventeen dose maximum).
Vitamin B1: Patients will also receive 200 mg of IV vitamin B1 every 12 hours in 50 mL of normal saline for four days or until ICU discharge (whichever happens first, nine dose maximum). | 54 |
| Placebo Patients in the control arm will receive the 100 mL of 0.9% sodium chloride every six hours and 50 mL of 0.9% sodium chloride every 12 hours to act as placebos for the vitamins C and B1 respectively. | 52 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 6 | 8 |
Baseline characteristics
| Characteristic | Vitamins C and B1 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 29 Participants | 30 Participants | 59 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 22 Participants | 47 Participants |
| Age, Continuous | 66 years | 69 years | 67 years |
| BMI | 28.4 kg/m^2 STANDARD_DEVIATION 7.6 | 29.7 kg/m^2 STANDARD_DEVIATION 7.6 | 29.0 kg/m^2 STANDARD_DEVIATION 7.6 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 54 Participants | 52 Participants | 106 Participants |
| Sex: Female, Male Female | 28 Participants | 23 Participants | 51 Participants |
| Sex: Female, Male Male | 26 Participants | 29 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 12 / 54 | 7 / 52 |
| other Total, other adverse events | 0 / 54 | 0 / 52 |
| serious Total, serious adverse events | 17 / 54 | 15 / 52 |
Outcome results
Primary
Mortality Rates
All-cause mortality from time of enrollment/treatment to 30 days post hospital discharge (up to 87 days)
Time frame: From time of treatment to 30 days post hospital discharge, up to 87 days.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vitamins C and B1 | Mortality Rates | 12 Participants |
| Placebo | Mortality Rates | 7 Participants |
p-value: 0.344Chi-squared
Secondary
Hospital Length of Stay
Total number of days patient is admitted to the hospital
Time frame: From admission to the hospital through hospital discharge, up to 57 days.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vitamins C and B1 | Hospital Length of Stay | 8.5 days |
| Placebo | Hospital Length of Stay | 7.0 days |
p-value: 0.526Chi-squared
Secondary
Hours on Vasopressors
Number of hours patient required vasopressors in norepinephrine equivalence.
Time frame: From admission to the ICU through discharge from the ICU, up to 25 days.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamins C and B1 | Hours on Vasopressors | 50.0 Hours | Standard Deviation 9.8 |
| Placebo | Hours on Vasopressors | 35.9 Hours | Standard Deviation 6.5 |
p-value: 0.236Chi-squared
Secondary
Intensive Care Unit Length of Stay
Total number of days patient is admitted to the ICU
Time frame: From time of admission to the ICU through discharge from the ICU, up to 25 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vitamins C and B1 | Intensive Care Unit Length of Stay | 3.5 days |
| Placebo | Intensive Care Unit Length of Stay | 3.0 days |
p-value: 0.123Chi-squared
Secondary
Readmission Rate
Readmission to the hospital within 30 days after discharge
Time frame: 30 days after hospital discharge
Population: 54 patients received treatment, 11 died during initial admission and therefore excluded from readmission statistics. Of the 52 patients in the control group 7 died during initial admission and were excluded from readmission statistics. One control patient was withdrawn and also could not be considered for readmission statistics.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vitamins C and B1 | Readmission Rate | 17 participants |
| Placebo | Readmission Rate | 15 participants |
p-value: 0.66Fisher Exact
Secondary
Ventilator Days
Number of days patient required ventilator
Time frame: From admission to the ICU through discharge from the ICU, up to 25 days.
Population: Intervention arm-1 patient made CMO and terminally extubated, 1 patient had insufficient data. Control-3 patients made CMO then terminally extubated
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamins C and B1 | Ventilator Days | 2.6 days on ventilator | Standard Deviation 3.5 |
| Placebo | Ventilator Days | 2.3 days on ventilator | Standard Deviation 5.8 |
p-value: 0.745t-test, 2 sided