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Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis (ACTS) Trial

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ClinicalTrials.gov Identifier: NCT03389555
Recruitment Status : Completed
First Posted : January 3, 2018
Results First Posted : January 29, 2021
Last Update Posted : February 16, 2021
Sponsor:
Collaborator:
Open Philanthropy Project
Information provided by (Responsible Party):
Michael Donnino, Beth Israel Deaconess Medical Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Sepsis
Septic Shock
Metabolic Disturbance
Interventions Drug: vitamin C, vitamin B1, hydrocortisone
Drug: Normal saline
Enrollment 205
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Vitamin C, Vitamin B1, Corticosteroids Placebo
Hide Arm/Group Description

The combination of vitamin C, vitamin B1, hydrocortisone :

  • Vitamin C (ascorbic acid) 1.5g every 6 hours x 4-days
  • Vitamin B1 (thiamine) 100mg every 6 hours x 4-days
  • Hydrocortisone 50mg every 6 hours x 4-days

vitamin C, vitamin B1, hydrocortisone: Vitamin C (1.5g) plus vitamin B1 (100mg) will be diluted in 100ml 0.9%NACL and administered IV every 6 hours for 4 days or until participant is discharged from the ICU. Hydrocortisone 50mg/ml will be administered via IV push over 1-2 minutes every 6hours for 4 days or until the patient is discharged from the ICU.

Normal Saline Solution (0.9%NaCl) in a volume to match all experimental arm components

Normal saline: Normal saline (0.9% NaCl solution) volume to match all components

Period Title: Overall Study
Started 103 102
Completed 101 99
Not Completed 2 3
Reason Not Completed
Protocol Violation             1             3
Death             1             0
Arm/Group Title Vitamin C, Vitamin B1, Corticosteroids Placebo Total
Hide Arm/Group Description

The combination of vitamin C, vitamin B1, hydrocortisone :

  • Vitamin C (ascorbic acid) 1.5g every 6 hours x 4-days
  • Vitamin B1 (thiamine) 100mg every 6 hours x 4-days
  • Hydrocortisone 50mg every 6 hours x 4-days

vitamin C, vitamin B1, hydrocortisone: Vitamin C (1.5g) plus vitamin B1 (100mg) will be diluted in 100ml 0.9%NACL and administered IV every 6 hours for 4 days or until participant is discharged from the ICU. Hydrocortisone 50mg/ml will be administered via IV push over 1-2 minutes every 6hours for 4 days or until the patient is discharged from the ICU.

Normal Saline Solution (0.9%NaCl) in a volume to match all experimental arm components

Normal saline: Normal saline (0.9% NaCl solution) volume to match all components

Total of all reporting groups
Overall Number of Baseline Participants 101 99 200
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 101 participants 99 participants 200 participants
68.9  (15.0) 67.7  (13.9) 68.2  (14.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 101 participants 99 participants 200 participants
Female
44
  43.6%
45
  45.5%
89
  44.5%
Male
57
  56.4%
54
  54.5%
111
  55.5%
Race/Ethnicity, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
White Number Analyzed 91 participants 93 participants 184 participants
68
  74.7%
73
  78.5%
141
  76.6%
Black Number Analyzed 91 participants 93 participants 184 participants
18
  19.8%
16
  17.2%
34
  18.5%
Asian Number Analyzed 91 participants 93 participants 184 participants
5
   5.5%
3
   3.2%
8
   4.3%
More than one Race Number Analyzed 91 participants 93 participants 184 participants
0
   0.0%
1
   1.1%
1
   0.5%
[1]
Measure Analysis Population Description: Excluded 10 patients in intervention arm and 6 patients in placebo arm who did not have race data available.
BMI, mean (SD)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 101 participants 99 participants 200 participants
28.8  (10.1) 27.9  (8.4) 28.3  (9.3)
Medical History,  
Measure Type: Count of Participants
Unit of measure:  Participants
# with Malignancy Number Analyzed 101 participants 99 participants 200 participants
26
  25.7%
32
  32.3%
58
  29.0%
# with Coronary Artery Disease Number Analyzed 101 participants 99 participants 200 participants
26
  25.7%
26
  26.3%
52
  26.0%
# with Congestive Heart Failure Number Analyzed 101 participants 99 participants 200 participants
14
  13.9%
23
  23.2%
37
  18.5%
Liver Disease Number Analyzed 101 participants 99 participants 200 participants
11
  10.9%
7
   7.1%
18
   9.0%
Primary Infectious Source   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Pneumonia Number Analyzed 94 participants 93 participants 187 participants
31
  33.0%
28
  30.1%
59
  31.6%
Intra-abdominal Number Analyzed 94 participants 93 participants 187 participants
30
  31.9%
23
  24.7%
53
  28.3%
Urinary Tract Infection Number Analyzed 94 participants 93 participants 187 participants
20
  21.3%
22
  23.7%
42
  22.5%
Other Number Analyzed 94 participants 93 participants 187 participants
13
  13.8%
20
  21.5%
33
  17.6%
[1]
Measure Analysis Population Description: Patients who did not have an identifiable primary infectious disease source were excluded from these tabulations (7 in intervention and 6 in placebo)
Volume of Intravenous Fluids Prior to Study Drug  
Median (Inter-Quartile Range)
Unit of measure:  mL
Number Analyzed 101 participants 99 participants 200 participants
2000
(1062 to 3000)
2000
(1125 to 3000)
2000
(1093.5 to 3000)
Time from Vasopressor Initiation to First Study Drug  
Median (Inter-Quartile Range)
Unit of measure:  Hours
Number Analyzed 101 participants 99 participants 200 participants
14.5
(8.1 to 19.1)
13.0
(7.5 to 20.5)
13.5
(8.0 to 19.8)
Time from Informed Consent to First Study Drug  
Median (Inter-Quartile Range)
Unit of measure:  Hours
Number Analyzed 101 participants 99 participants 200 participants
2.2
(1.7 to 3.0)
2.0
(1.5 to 2.7)
2.1
(1.6 to 2.9)
Baseline Cardiovascular Component of Total SOFA Score   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Units on a scale
Number Analyzed 101 participants 99 participants 200 participants
4
(3 to 4)
4
(3 to 4)
4
(3 to 4)
[1]
Measure Description: Baseline Cardiovascular Component of the Sequential Organ Failure Assessment (SOFA) score: The cardiovascular component of the SOFA score ranges from 0 (best) to 4 (worst), with a score of 0 indicating a mean arterial pressure of ≥ 70 mmHg, a score of 1 indicating a mean arterial pressure of < 70 mmHg, a score of 2 indicating dopamine dosing of ≤ 5 µg/kg/min or any dose of dobutamine, a score of 3 indicating norepinephrine dosing of ≤1mcg/kg/min (or equivalent) and a score of 4 indicating a norepinephrine dose >1mcg/kg/min (or equivalent).
# on Mechanical Ventilation  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 101 participants 99 participants 200 participants
48
  47.5%
44
  44.4%
92
  46.0%
# with Acute Respiratory Distress Syndrome  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 101 participants 99 participants 200 participants
22
  21.8%
18
  18.2%
40
  20.0%
30 Day Predicted Survival   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
High Likelihood Number Analyzed 101 participants 99 participants 200 participants
34
  33.7%
38
  38.4%
72
  36.0%
Uncertain Number Analyzed 101 participants 99 participants 200 participants
61
  60.4%
54
  54.5%
115
  57.5%
Low Likelihood Number Analyzed 101 participants 99 participants 200 participants
6
   5.9%
7
   7.1%
13
   6.5%
[1]
Measure Description: At time of enrollment, the physician enrolling the patient is asked to predict the patient's chances of survival at the time-point 30 days after enrollment.
Lactate  
Median (Inter-Quartile Range)
Unit of measure:  mmol/L
Number Analyzed 101 participants 99 participants 200 participants
1.8
(1.3 to 2.9)
1.8
(1.4 to 2.8)
1.8
(1.3 to 2.8)
1.Primary Outcome
Title Sequential Organ Failure Assessment (SOFA) Score at Baseline and 72 Hours
Hide Description Sequential Organ Failure Assessment (SOFA) Score at Baseline and 72 Hours. The SOFA score ranges from a minimum of 0 to a maximum of 24, with higher scores meaning worse outcomes.
Time Frame Enrollment to 72-hours
Hide Outcome Measure Data
Hide Analysis Population Description
For the 72 hour SOFA score, patients who expired prior to that time point are excluded from the calculation of mean (SD) of the 72 hour SOFA score.
Arm/Group Title Vitamin C, Vitamin B1, Corticosteroids Placebo
Hide Arm/Group Description:

The combination of vitamin C, vitamin B1, hydrocortisone :

  • Vitamin C (ascorbic acid) 1.5g every 6 hours x 4-days
  • Vitamin B1 (thiamine) 100mg every 6 hours x 4-days
  • Hydrocortisone 50mg every 6 hours x 4-days

vitamin C, vitamin B1, hydrocortisone: Vitamin C (1.5g) plus vitamin B1 (100mg) will be diluted in 100ml 0.9%NACL and administered IV every 6 hours for 4 days or until participant is discharged from the ICU. Hydrocortisone 50mg/ml will be administered via IV push over 1-2 minutes every 6hours for 4 days or until the patient is discharged from the ICU.

Normal Saline Solution (0.9%NaCl) in a volume to match all experimental arm components

Normal saline: Normal saline (0.9% NaCl solution) volume to match all components

Overall Number of Participants Analyzed 101 99
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Enrollment SOFA score Number Analyzed 101 participants 99 participants
9.1  (3.5) 9.2  (3.2)
72 hour SOFA score Number Analyzed 90 participants 88 participants
4.4  (4.1) 5.1  (4.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vitamin C, Vitamin B1, Corticosteroids, Placebo
Comments The primary outcome was analyzed using a linear mixed-effects model where the correlation of within-patient repeated SOFA score measures was accounted for via the use of an unstructured variance-covariance matrix and linear contrasts. Covariates included age, sex, treatment group, time, and the interaction between treatment group and time. Study site was included as a random intercept. The model estimates the mean difference in SOFA score at 72 hours between treatment and control groups.
Type of Statistical Test Equivalence
Comments Equivalence margin: if confidence interval for mean difference between SOFA scores at 72 hour time-point for two groups overlaps 0 (p-value > 0.05) scores considered to be equivalent. Note: The model estimates the mean difference in SOFA score at 72 hours between treatment and control groups, for those patient for whom a SOFA score could be calculated at the 72 hour time point (i.e patients that were alive at the 72 hour time point, 90 patients in the treatment and 88 patients in the control).
Statistical Test of Hypothesis P-Value 0.12
Comments A priori threshold for significance, p-value < 0.05
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-1.7 to 0.2
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Renal Failure
Hide Description

Development of renal failure as defined by a Kidney Disease Improving Global Outcomes [KDIGO] stage 3 or higher. There are 3 stages in the KDIGO scale with stage 3 being the worst (corresponds to renal failure).

Stage 1- serum creatinine 1.5 to 1.9 times baseline OR an increase in serum creatinine ≥ 0.3 mg/dL OR urine output < 0.5ml/kg/hour for 6-12 hours. Stage 2- serum creatinine 2.0-2.9 times baseline OR urine output <0.5mg/kg/hour for ≥ 12 hours Stage 3- serum creatinine 3.0 times baseline (or serum creatinine of more than or equal to 4.0 mg/dl with an acute increase of at least 0.5 mg/dl) (OR) Urine output less than 0.3 ml/kg/hour for 24 hours or anuria for 12 hours or new renal replacement therapy

Time Frame Enrollment until 7-days or discharge from the ICU
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vitamin C, Vitamin B1, Corticosteroids Placebo
Hide Arm/Group Description:

The combination of vitamin C, vitamin B1, hydrocortisone :

  • Vitamin C (ascorbic acid) 1.5g every 6 hours x 4-days
  • Vitamin B1 (thiamine) 100mg every 6 hours x 4-days
  • Hydrocortisone 50mg every 6 hours x 4-days

vitamin C, vitamin B1, hydrocortisone: Vitamin C (1.5g) plus vitamin B1 (100mg) will be diluted in 100ml 0.9%NACL and administered IV every 6 hours for 4 days or until participant is discharged from the ICU. Hydrocortisone 50mg/ml will be administered via IV push over 1-2 minutes every 6hours for 4 days or until the patient is discharged from the ICU.

Normal Saline Solution (0.9%NaCl) in a volume to match all experimental arm components

Normal saline: Normal saline (0.9% NaCl solution) volume to match all components

Overall Number of Participants Analyzed 101 99
Measure Type: Count of Participants
Unit of Measure: Participants
32
  31.7%
27
  27.3%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vitamin C, Vitamin B1, Corticosteroids, Placebo
Comments Logistic regression analysis evaluating the key secondary outcome of kidney failure in treatment group (intervention versus placebo) controlling for treatment site.
Type of Statistical Test Equivalence
Comments For the key secondary outcome of kidney failure, 200 patients were estimated to provide 94% power, assuming that 30% of participants in the treatment group and 55% in the placebo group would develop kidney failure. If the adjusted risk difference from the logistic regression analysis overlaps 0, there was considered to be no difference between groups
Statistical Test of Hypothesis P-Value 0.58
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 3.0
Confidence Interval (2-Sided) 95%
-10.0 to 20.0
Estimation Comments [Not Specified]
3.Secondary Outcome
Title 30-day Mortality
Hide Description Mortality rate
Time Frame Enrollment until 30-days after enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vitamin C, Vitamin B1, Corticosteroids Placebo
Hide Arm/Group Description:

The combination of vitamin C, vitamin B1, hydrocortisone :

  • Vitamin C (ascorbic acid) 1.5g every 6 hours x 4-days
  • Vitamin B1 (thiamine) 100mg every 6 hours x 4-days
  • Hydrocortisone 50mg every 6 hours x 4-days

vitamin C, vitamin B1, hydrocortisone: Vitamin C (1.5g) plus vitamin B1 (100mg) will be diluted in 100ml 0.9%NACL and administered IV every 6 hours for 4 days or until participant is discharged from the ICU. Hydrocortisone 50mg/ml will be administered via IV push over 1-2 minutes every 6hours for 4 days or until the patient is discharged from the ICU.

Normal Saline Solution (0.9%NaCl) in a volume to match all experimental arm components

Normal saline: Normal saline (0.9% NaCl solution) volume to match all components

Overall Number of Participants Analyzed 101 99
Measure Type: Count of Participants
Unit of Measure: Participants
35
  34.7%
29
  29.3%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vitamin C, Vitamin B1, Corticosteroids, Placebo
Comments Cox Regression controlling for site used to identify hazard ratio for outcome of death for treatment versus intervention group. Null hypothesis is that hazard ratio is 1.
Type of Statistical Test Equivalence
Comments If confidence interval for hazard ratio crosses 0, hazard of death assumed to be equivalent in the two groups.
Statistical Test of Hypothesis P-Value 0.05
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
0.8 to 2.2
Estimation Comments [Not Specified]
4.Other Pre-specified Outcome
Title Ventilator Free Days
Hide Description Days not receiving invasive mechanical ventilation
Time Frame Ventilator free days over the first 7-days after enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vitamin C, Vitamin B1, Corticosteroids Placebo
Hide Arm/Group Description:

The combination of vitamin C, vitamin B1, hydrocortisone :

  • Vitamin C (ascorbic acid) 1.5g every 6 hours x 4-days
  • Vitamin B1 (thiamine) 100mg every 6 hours x 4-days
  • Hydrocortisone 50mg every 6 hours x 4-days

vitamin C, vitamin B1, hydrocortisone: Vitamin C (1.5g) plus vitamin B1 (100mg) will be diluted in 100ml 0.9%NACL and administered IV every 6 hours for 4 days or until participant is discharged from the ICU. Hydrocortisone 50mg/ml will be administered via IV push over 1-2 minutes every 6hours for 4 days or until the patient is discharged from the ICU.

Normal Saline Solution (0.9%NaCl) in a volume to match all experimental arm components

Normal saline: Normal saline (0.9% NaCl solution) volume to match all components

Overall Number of Participants Analyzed 101 99
Median (Inter-Quartile Range)
Unit of Measure: Days
6
(2 to 7)
6
(0 to 7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vitamin C, Vitamin B1, Corticosteroids, Placebo
Comments Quantile regression controlling for site performed to compare treatment and control group's ventilator free days.
Type of Statistical Test Equivalence
Comments If the confidence interval for the median difference in ventilator free days between groups crosses 0, the two groups are considered equivalent.
Statistical Test of Hypothesis P-Value >0.99
Comments [Not Specified]
Method Quantile Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-1.9 to 1.9
Estimation Comments [Not Specified]
5.Other Pre-specified Outcome
Title Shock Free Days
Hide Description Days not receiving vasopressor
Time Frame Vasopressor free days over the first 7-days after enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vitamin C, Vitamin B1, Corticosteroids Placebo
Hide Arm/Group Description:

The combination of vitamin C, vitamin B1, hydrocortisone :

  • Vitamin C (ascorbic acid) 1.5g every 6 hours x 4-days
  • Vitamin B1 (thiamine) 100mg every 6 hours x 4-days
  • Hydrocortisone 50mg every 6 hours x 4-days

vitamin C, vitamin B1, hydrocortisone: Vitamin C (1.5g) plus vitamin B1 (100mg) will be diluted in 100ml 0.9%NACL and administered IV every 6 hours for 4 days or until participant is discharged from the ICU. Hydrocortisone 50mg/ml will be administered via IV push over 1-2 minutes every 6hours for 4 days or until the patient is discharged from the ICU.

Normal Saline Solution (0.9%NaCl) in a volume to match all experimental arm components

Normal saline: Normal saline (0.9% NaCl solution) volume to match all components

Overall Number of Participants Analyzed 101 99
Median (Inter-Quartile Range)
Unit of Measure: Days
5
(3 to 5)
4
(1 to 5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vitamin C, Vitamin B1, Corticosteroids, Placebo
Comments Quantile regression controlling for site performed to compare treatment and control group's shock free days.
Type of Statistical Test Equivalence
Comments If the confidence interval for the median difference in shock free days between groups crosses 0, the two groups are considered equivalent.
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Quantile Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
0.2 to 1.8
Estimation Comments [Not Specified]
6.Other Pre-specified Outcome
Title ICU Free Days
Hide Description Number of days that the patient was not in the ICU. Timeframe listed below.
Time Frame From enrollment until 28 days after enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vitamin C, Vitamin B1, Corticosteroids Placebo
Hide Arm/Group Description:

The combination of vitamin C, vitamin B1, hydrocortisone :

  • Vitamin C (ascorbic acid) 1.5g every 6 hours x 4-days
  • Vitamin B1 (thiamine) 100mg every 6 hours x 4-days
  • Hydrocortisone 50mg every 6 hours x 4-days

vitamin C, vitamin B1, hydrocortisone: Vitamin C (1.5g) plus vitamin B1 (100mg) will be diluted in 100ml 0.9%NACL and administered IV every 6 hours for 4 days or until participant is discharged from the ICU. Hydrocortisone 50mg/ml will be administered via IV push over 1-2 minutes every 6hours for 4 days or until the patient is discharged from the ICU.

Normal Saline Solution (0.9%NaCl) in a volume to match all experimental arm components

Normal saline: Normal saline (0.9% NaCl solution) volume to match all components

Overall Number of Participants Analyzed 101 99
Median (Inter-Quartile Range)
Unit of Measure: Days
22
(3 to 25)
21
(4 to 25)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vitamin C, Vitamin B1, Corticosteroids, Placebo
Comments Quantile regression controlling for site performed to compare treatment and control group's ICU free days.
Type of Statistical Test Equivalence
Comments If the confidence interval for the median difference in ICU free days between groups crosses 0, the two groups are considered equivalent.
Statistical Test of Hypothesis P-Value 0.69
Comments [Not Specified]
Method Quantile Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
-3.0 to 6.0
Estimation Comments [Not Specified]
7.Other Pre-specified Outcome
Title Hospital Mortality
Hide Description Hospital mortality rate
Time Frame Enrollment until hospital discharge, death, or 30-days. Whichever comes first.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vitamin C, Vitamin B1, Corticosteroids Placebo
Hide Arm/Group Description:

The combination of vitamin C, vitamin B1, hydrocortisone :

  • Vitamin C (ascorbic acid) 1.5g every 6 hours x 4-days
  • Vitamin B1 (thiamine) 100mg every 6 hours x 4-days
  • Hydrocortisone 50mg every 6 hours x 4-days

vitamin C, vitamin B1, hydrocortisone: Vitamin C (1.5g) plus vitamin B1 (100mg) will be diluted in 100ml 0.9%NACL and administered IV every 6 hours for 4 days or until participant is discharged from the ICU. Hydrocortisone 50mg/ml will be administered via IV push over 1-2 minutes every 6hours for 4 days or until the patient is discharged from the ICU.

Normal Saline Solution (0.9%NaCl) in a volume to match all experimental arm components

Normal saline: Normal saline (0.9% NaCl solution) volume to match all components

Overall Number of Participants Analyzed 101 99
Measure Type: Count of Participants
Unit of Measure: Participants
28
  27.7%
23
  23.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vitamin C, Vitamin B1, Corticosteroids, Placebo
Comments Logistic regression analysis evaluating the key secondary outcome of hospital mortality in treatment group (intervention versus placebo) controlling for treatment site..
Type of Statistical Test Equivalence
Comments If the adjusted risk difference from the logistic regression analysis overlaps 0, there was considered to be no difference between groups
Statistical Test of Hypothesis P-Value 0.55
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 3.0
Confidence Interval (2-Sided) 95%
-10.0 to 20.0
Estimation Comments [Not Specified]
8.Other Pre-specified Outcome
Title Intensive Care Unit (ICU) Mortality
Hide Description ICU mortality rate
Time Frame Enrollment until ICU discharge, death, or 30-days. Whichever comes first.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vitamin C, Vitamin B1, Corticosteroids Placebo
Hide Arm/Group Description:

The combination of vitamin C, vitamin B1, hydrocortisone :

  • Vitamin C (ascorbic acid) 1.5g every 6 hours x 4-days
  • Vitamin B1 (thiamine) 100mg every 6 hours x 4-days
  • Hydrocortisone 50mg every 6 hours x 4-days

vitamin C, vitamin B1, hydrocortisone: Vitamin C (1.5g) plus vitamin B1 (100mg) will be diluted in 100ml 0.9%NACL and administered IV every 6 hours for 4 days or until participant is discharged from the ICU. Hydrocortisone 50mg/ml will be administered via IV push over 1-2 minutes every 6hours for 4 days or until the patient is discharged from the ICU.

Normal Saline Solution (0.9%NaCl) in a volume to match all experimental arm components

Normal saline: Normal saline (0.9% NaCl solution) volume to match all components

Overall Number of Participants Analyzed 101 99
Measure Type: Count of Participants
Unit of Measure: Participants
23
  22.8%
20
  20.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vitamin C, Vitamin B1, Corticosteroids, Placebo
Comments Logistic regression analysis evaluating the key secondary outcome of ICU mortality in treatment group (intervention versus placebo) controlling for treatment site.
Type of Statistical Test Equivalence
Comments If the adjusted risk difference from the logistic regression analysis overlaps 0, there was considered to be no difference between groups
Statistical Test of Hypothesis P-Value 0.80
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 2.0
Confidence Interval (2-Sided) 95%
-10.0 to 10.0
Estimation Comments [Not Specified]
9.Other Pre-specified Outcome
Title Number of Participants With Delirium
Hide Description

Describes if patient has delirium as defined by the Confusion Assessment Method (CAM)-ICU. The CAM-ICU method requires that the patient have 3 features to qualify for delirium:

  1. Acute Onset of Changes or Fluctuations in the Course of Mental Status (AND )
  2. Inattention (AND)
  3. Disorganized thinking (OR) Altered Level of Consciousness
Time Frame On day 3 (at approximately 72 hours) after the first study drug dose
Hide Outcome Measure Data
Hide Analysis Population Description
We were able to assess CAM-ICU delirium on day 3 in only 83 patients from treatment and 76 patients from the control arm (unable to assess for remaining patients due to death or discharge)
Arm/Group Title Vitamin C, Vitamin B1, Corticosteroids Placebo
Hide Arm/Group Description:

The combination of vitamin C, vitamin B1, hydrocortisone :

  • Vitamin C (ascorbic acid) 1.5g every 6 hours x 4-days
  • Vitamin B1 (thiamine) 100mg every 6 hours x 4-days
  • Hydrocortisone 50mg every 6 hours x 4-days

vitamin C, vitamin B1, hydrocortisone: Vitamin C (1.5g) plus vitamin B1 (100mg) will be diluted in 100ml 0.9%NACL and administered IV every 6 hours for 4 days or until participant is discharged from the ICU. Hydrocortisone 50mg/ml will be administered via IV push over 1-2 minutes every 6hours for 4 days or until the patient is discharged from the ICU.

Normal Saline Solution (0.9%NaCl) in a volume to match all experimental arm components

Normal saline: Normal saline (0.9% NaCl solution) volume to match all components

Overall Number of Participants Analyzed 83 76
Measure Type: Count of Participants
Unit of Measure: Participants
31
  37.3%
35
  46.1%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vitamin C, Vitamin B1, Corticosteroids, Placebo
Comments Logistic regression analysis evaluating the key secondary outcome of occurrence of delirium in treatment group (intervention versus placebo) controlling for treatment site.
Type of Statistical Test Equivalence
Comments If the adjusted risk difference from the logistic regression analysis overlaps 0, there was considered to be no difference between groups
Statistical Test of Hypothesis P-Value 0.16
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -12
Confidence Interval (2-Sided) 95%
-25 to 4
Estimation Comments [Not Specified]
10.Other Pre-specified Outcome
Title Hospital Disposition: Survivors Discharged Home
Hide Description Home hospital disposition in patients who survive to discharge
Time Frame Enrollment until hospital discharge, death, or 30-days, whichever comes first.
Hide Outcome Measure Data
Hide Analysis Population Description
Population of patients who survived to hospital discharge. 73 patients in the treatment group and 76 patients in the control group survived to hospital discharge..
Arm/Group Title Vitamin C, Vitamin B1, Corticosteroids Placebo
Hide Arm/Group Description:

The combination of vitamin C, vitamin B1, hydrocortisone :

  • Vitamin C (ascorbic acid) 1.5g every 6 hours x 4-days
  • Vitamin B1 (thiamine) 100mg every 6 hours x 4-days
  • Hydrocortisone 50mg every 6 hours x 4-days

vitamin C, vitamin B1, hydrocortisone: Vitamin C (1.5g) plus vitamin B1 (100mg) will be diluted in 100ml 0.9%NACL and administered IV every 6 hours for 4 days or until participant is discharged from the ICU. Hydrocortisone 50mg/ml will be administered via IV push over 1-2 minutes every 6hours for 4 days or until the patient is discharged from the ICU.

Normal Saline Solution (0.9%NaCl) in a volume to match all experimental arm components

Normal saline: Normal saline (0.9% NaCl solution) volume to match all components

Overall Number of Participants Analyzed 73 76
Measure Type: Count of Participants
Unit of Measure: Participants
34
  46.6%
35
  46.1%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vitamin C, Vitamin B1, Corticosteroids, Placebo
Comments Logistic regression analysis evaluating home hospital disposition in survivors to hospital discharge in intervention versus placebo group controlling for treatment site.
Type of Statistical Test Equivalence
Comments If the adjusted risk difference from the logistic regression analysis overlaps 0, there was considered to be no difference between groups
Statistical Test of Hypothesis P-Value 0.82
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -1.8
Confidence Interval (2-Sided) 95%
-18 to 14
Estimation Comments [Not Specified]
Time Frame Time from enrollment to hospital discharge, an average of 13.5 days for all patients
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Vitamin C, Vitamin B1, Corticosteroids Placebo
Hide Arm/Group Description

The combination of vitamin C, vitamin B1, hydrocortisone :

  • Vitamin C (ascorbic acid) 1.5g every 6 hours x 4-days
  • Vitamin B1 (thiamine) 100mg every 6 hours x 4-days
  • Hydrocortisone 50mg every 6 hours x 4-days

vitamin C, vitamin B1, hydrocortisone: Vitamin C (1.5g) plus vitamin B1 (100mg) will be diluted in 100ml 0.9%NACL and administered IV every 6 hours for 4 days or until participant is discharged from the ICU. Hydrocortisone 50mg/ml will be administered via IV push over 1-2 minutes every 6hours for 4 days or until the patient is discharged from the ICU.

Normal Saline Solution (0.9%NaCl) in a volume to match all experimental arm components

Normal saline: Normal saline (0.9% NaCl solution) volume to match all components

All-Cause Mortality
Vitamin C, Vitamin B1, Corticosteroids Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   35/101 (34.65%)      29/99 (29.29%)    
Hide Serious Adverse Events
Vitamin C, Vitamin B1, Corticosteroids Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/101 (12.87%)      12/99 (12.12%)    
Endocrine disorders     
Hyperglycemia   12/101 (11.88%)  101 7/99 (7.07%)  99
Infections and infestations     
New Hospital Acquired Infection   13/101 (12.87%)  101 12/99 (12.12%)  99
Metabolism and nutrition disorders     
Hypernatremia   11/101 (10.89%)  101 7/99 (7.07%)  99
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Vitamin C, Vitamin B1, Corticosteroids Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/101 (0.00%)      0/99 (0.00%)    
Ongoing or planned corticosteroid use was the most common exclusion criterion, perhaps eliminating a subset of patients more likely to benefit from corticosteroids. Some patients were discharged alive from the ICU within 96 hours of enrollment; thus, many patients did not receive a full 4 days of study drug
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Michae Donnino
Organization: Beth Israel Deaconness Medical Center Emergency Department
Phone: (617) 754-2882
EMail: mdonnino@bidmc.harvard.edu
Layout table for additonal information
Responsible Party: Michael Donnino, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT03389555    
Other Study ID Numbers: 2017P000436
First Submitted: December 27, 2017
First Posted: January 3, 2018
Results First Submitted: November 24, 2020
Results First Posted: January 29, 2021
Last Update Posted: February 16, 2021