Trial Outcomes & Findings for Vitamin C & Thiamine to Treat Sepsis and Septic Shock (NCT NCT03592277)
NCT ID: NCT03592277
Last Updated: 2022-09-28
Results Overview
All-cause mortality from time of enrollment/treatment to 30 days post hospital discharge (up to 87 days)
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
120 participants
Primary outcome timeframe
From time of treatment to 30 days post hospital discharge, up to 87 days.
Results posted on
2022-09-28
Participant Flow
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.
The only exclusions for for patients who opted out of the study following initial consent. No other run-in events occurred.
Participant milestones
| Measure |
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).
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
60
|
60
|
|
Overall Study
Powered For
|
60
|
60
|
|
Overall Study
COMPLETED
|
54
|
52
|
|
Overall Study
NOT COMPLETED
|
6
|
8
|
Reasons for withdrawal
| Measure |
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).
|
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.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
6
|
8
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Vitamins C and B1
n=54 Participants
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).
|
Placebo
n=52 Participants
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.
|
Total
n=106 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=54 Participants
|
0 Participants
n=52 Participants
|
0 Participants
n=106 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
25 Participants
n=54 Participants
|
22 Participants
n=52 Participants
|
47 Participants
n=106 Participants
|
|
Age, Categorical
>=65 years
|
29 Participants
n=54 Participants
|
30 Participants
n=52 Participants
|
59 Participants
n=106 Participants
|
|
Age, Continuous
|
66 years
n=54 Participants
|
69 years
n=52 Participants
|
67 years
n=106 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=54 Participants
|
23 Participants
n=52 Participants
|
51 Participants
n=106 Participants
|
|
Sex: Female, Male
Male
|
26 Participants
n=54 Participants
|
29 Participants
n=52 Participants
|
55 Participants
n=106 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
United States
|
54 Participants
n=54 Participants
|
52 Participants
n=52 Participants
|
106 Participants
n=106 Participants
|
|
BMI
|
28.4 kg/m^2
STANDARD_DEVIATION 7.6 • n=54 Participants
|
29.7 kg/m^2
STANDARD_DEVIATION 7.6 • n=52 Participants
|
29.0 kg/m^2
STANDARD_DEVIATION 7.6 • n=106 Participants
|
PRIMARY outcome
Timeframe: 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)
Outcome measures
| Measure |
Vitamins C and B1
n=54 Participants
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).
Patients may remain in the ICU and/or hospitalized after completing 4 days of treatment.
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).
|
Placebo
n=52 Participants
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.
|
|---|---|---|
|
Mortality Rates
|
12 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: From admission to the hospital through hospital discharge, up to 57 days.Total number of days patient is admitted to the hospital
Outcome measures
| Measure |
Vitamins C and B1
n=54 Participants
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).
Patients may remain in the ICU and/or hospitalized after completing 4 days of treatment.
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).
|
Placebo
n=52 Participants
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.
|
|---|---|---|
|
Hospital Length of Stay
|
8.5 days
Interval 7.0 to 13.0
|
7.0 days
Interval 5.5 to 11.5
|
SECONDARY outcome
Timeframe: From time of admission to the ICU through discharge from the ICU, up to 25 daysTotal number of days patient is admitted to the ICU
Outcome measures
| Measure |
Vitamins C and B1
n=54 Participants
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).
Patients may remain in the ICU and/or hospitalized after completing 4 days of treatment.
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).
|
Placebo
n=52 Participants
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.
|
|---|---|---|
|
Intensive Care Unit Length of Stay
|
3.5 days
Interval 2.0 to 7.0
|
3.0 days
Interval 2.0 to 4.0
|
SECONDARY outcome
Timeframe: 30 days after hospital dischargePopulation: 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.
Readmission to the hospital within 30 days after discharge
Outcome measures
| Measure |
Vitamins C and B1
n=43 Participants
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).
Patients may remain in the ICU and/or hospitalized after completing 4 days of treatment.
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).
|
Placebo
n=44 Participants
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.
|
|---|---|---|
|
Readmission Rate
|
17 participants
|
15 participants
|
SECONDARY outcome
Timeframe: 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
Number of days patient required ventilator
Outcome measures
| Measure |
Vitamins C and B1
n=52 Participants
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).
Patients may remain in the ICU and/or hospitalized after completing 4 days of treatment.
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).
|
Placebo
n=49 Participants
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.
|
|---|---|---|
|
Ventilator Days
|
2.6 days on ventilator
Standard Deviation 3.5
|
2.3 days on ventilator
Standard Deviation 5.8
|
SECONDARY outcome
Timeframe: From admission to the ICU through discharge from the ICU, up to 25 days.Number of hours patient required vasopressors in norepinephrine equivalence.
Outcome measures
| Measure |
Vitamins C and B1
n=54 Participants
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).
Patients may remain in the ICU and/or hospitalized after completing 4 days of treatment.
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).
|
Placebo
n=52 Participants
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.
|
|---|---|---|
|
Hours on Vasopressors
|
50.0 Hours
Standard Deviation 9.8
|
35.9 Hours
Standard Deviation 6.5
|
Adverse Events
Vitamins C and B1
Serious events: 17 serious events
Other events: 0 other events
Deaths: 12 deaths
Placebo
Serious events: 15 serious events
Other events: 0 other events
Deaths: 7 deaths
Serious adverse events
| Measure |
Vitamins C and B1
n=54 participants at risk
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).
|
Placebo
n=52 participants at risk
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.
|
|---|---|---|
|
Infections and infestations
Death due to sepsis or septic shock
|
22.2%
12/54 • Number of events 12 • Adverse events were collected from the time of enrollment into the study, during hospital stay and continued until 30 days following discharge from the hospital, up to 87 days.
|
13.5%
7/52 • Number of events 7 • Adverse events were collected from the time of enrollment into the study, during hospital stay and continued until 30 days following discharge from the hospital, up to 87 days.
|
|
Infections and infestations
Readmissions within 30 days
|
31.5%
17/54 • Number of events 17 • Adverse events were collected from the time of enrollment into the study, during hospital stay and continued until 30 days following discharge from the hospital, up to 87 days.
|
28.8%
15/52 • Number of events 15 • Adverse events were collected from the time of enrollment into the study, during hospital stay and continued until 30 days following discharge from the hospital, up to 87 days.
|
Other adverse events
Adverse event data not reported
Additional Information
David Shapiro, MD, MHCM, FACS, FCCM CMO of Saint Francis Hospital and Medical Center
Saint Francis Hospital and Medical Center
Phone: 860-833-5673
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place