Trial Outcomes & Findings for Vitamin C Infusion for TReatment in Sepsis and Alcoholic Hepatitis (NCT NCT03829683)

NCT ID: NCT03829683

Last Updated: 2023-08-28

Results Overview

Change in MELD score from Day 0 to Day 4. MELD score ranges from 6 (least sick) to 40 (most sick) based on blood tests which ranks the degree of sickness from liver disease. The lab tests used to determine the MELD score are creatinine, bilirubin, and international normalized ratio (INR).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 20 participants
• Primary outcome timeframe: Baseline and 96 hours
• Results posted on: 2023-08-28

Participant Flow

Participant milestones

Measure	Vitamin C Infusion (Ascorbic Acid) Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours	Placebo Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours
Overall Study STARTED	10	10
Overall Study COMPLETED	5	8
Overall Study NOT COMPLETED	5	2

Reasons for withdrawal

Measure	Vitamin C Infusion (Ascorbic Acid) Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours	Placebo Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours
Overall Study Lost to Follow-up	1	0
Overall Study Physician Decision	3	1
Overall Study Withdrawal by Subject	0	1
Overall Study Discharge from hospital	1	0

Baseline Characteristics

Vitamin C Infusion for TReatment in Sepsis and Alcoholic Hepatitis

Baseline characteristics by cohort

Measure	Vitamin C Infusion (Ascorbic Acid) n=10 Participants Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours	Placebo n=10 Participants Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours	Total n=20 Participants Total of all reporting groups
Age, Continuous	40.1 years STANDARD_DEVIATION 9.5 • n=5 Participants	48.4 years STANDARD_DEVIATION 14.9 • n=7 Participants	46.9 years STANDARD_DEVIATION 12.5 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants	10 participants n=7 Participants	20 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 96 hours

Population: Labs were not collected from 4 participants on day 4 so change in MELD score could not be calculated for those participants and they are omitted from the analysis.

Change in MELD score from Day 0 to Day 4. MELD score ranges from 6 (least sick) to 40 (most sick) based on blood tests which ranks the degree of sickness from liver disease. The lab tests used to determine the MELD score are creatinine, bilirubin, and international normalized ratio (INR).

Outcome measures

Measure	Vitamin C Infusion (Ascorbic Acid) n=8 Participants Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours	Placebo n=8 Participants Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours
Change in Model for End Stage Liver Disease (MELD) Score All patients	-0.13 score on a scale Standard Deviation 7.0	-2.9 score on a scale Standard Deviation 3.3
Change in Model for End Stage Liver Disease (MELD) Score Patients alive at 4 weeks	-2.3 score on a scale Standard Deviation 5.2	-2.4 score on a scale Standard Deviation 1.3

SECONDARY outcome

Timeframe: Baseline and 96 hours

Population: Data not recorded for all participants

A number that ranges from 0 (least sick) to 24 (most sick) and ranks the degree of sickness from liver failure and several other organ systems in a critically ill person. The score is determined by evaluating a person's liver function, kidney function, nervous system (brain), coagulation (blood clotting), circulation (blood pressure), and respiratory status (breathing)

Outcome measures

Measure	Vitamin C Infusion (Ascorbic Acid) n=1 Participants Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours	Placebo n=4 Participants Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours
Change in Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) Score Baseline	14 score on a scale Standard Deviation NA Only 1 participant in this arm	15.33 score on a scale Standard Deviation 0.577
Change in Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) Score Day 4	—	12.75 score on a scale Standard Deviation 1.708

SECONDARY outcome

Timeframe: Baseline and 96 hours

Standard blood test used to determine the severity and nature of liver problems.

Outcome measures

Measure	Vitamin C Infusion (Ascorbic Acid) n=7 Participants Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours	Placebo n=8 Participants Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours
Change in Aspartate Aminotransferase (AST) Level	176.0 IU/L Standard Deviation 466.28	-16.5 IU/L Standard Deviation 53.07

SECONDARY outcome

Timeframe: Baseline and 96 hours

Standard blood test used to determine the severity and nature of liver problems.

Outcome measures

Measure	Vitamin C Infusion (Ascorbic Acid) n=7 Participants Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours	Placebo n=8 Participants Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours
Change in Alanine Aminotransferase (ALT) Level	62.71 IU/L Standard Deviation 155.26	1.00 IU/L Standard Deviation 14.65

SECONDARY outcome

Timeframe: Baseline and 96 hours

Standard blood test used to determine the severity and nature of liver problems.

Outcome measures

Measure	Vitamin C Infusion (Ascorbic Acid) n=7 Participants Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours	Placebo n=8 Participants Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours
Change in Total Bilirubin	-0.30 mg/dL Standard Deviation 5.69	0.45 mg/dL Standard Deviation 5.79

SECONDARY outcome

Timeframe: Baseline and 96 hours

Standard blood test used to determine the severity and nature of liver problems.

Outcome measures

Measure	Vitamin C Infusion (Ascorbic Acid) n=7 Participants Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours	Placebo n=8 Participants Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours
Change in Alkaline Phosphatase	-5.71 U/L Standard Deviation 67.90	-7.50 U/L Standard Deviation 52.86

SECONDARY outcome

Timeframe: Baseline and 96 hours

Standard blood test used to determine the severity and nature of liver problems.

Outcome measures

Measure	Vitamin C Infusion (Ascorbic Acid) n=7 Participants Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours	Placebo n=8 Participants Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours
Change in Albumin	-0.10 g/dL Standard Deviation 0.71	0.06 g/dL Standard Deviation 0.99

SECONDARY outcome

Timeframe: up to 96 hours

Observation about the need to change the dose of study medication and symptoms such as headache, dizziness, dry mouth, nausea, vomiting, flushing, rash, or hypotension (low blood pressure)

Outcome measures

Measure	Vitamin C Infusion (Ascorbic Acid) n=10 Participants Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours	Placebo n=10 Participants Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours
Number of Treatment-related Adverse Events as Assessed by CTCAE v5.0	12 Adverse Events	11 Adverse Events

SECONDARY outcome

Timeframe: Baseline and 96 hours

An electrocardiogram (ECG or test of the electrical activity of the heart) is performed to determine if there are changes to the heart rhythm.

Outcome measures

Measure	Vitamin C Infusion (Ascorbic Acid) n=6 Participants Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours	Placebo n=6 Participants Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours
Changes to Corrected QT Interval (QTc)	-10.00 milliseconds Standard Deviation 29.47	-58.17 milliseconds Standard Deviation 88.56

SECONDARY outcome

Timeframe: Baseline and 96 hours

Urine samples are collected to determine changes in pH (acidity) that could indicate a risk for kidney stones. The pH scale ranges from 0 to 14, with smaller numbers meaning more acidic and higher numbers meaning more basic. A pH of 7 is considered to be neutral. Normal levels of urine pH range from 4.6 - 8 on the pH scale.

Outcome measures

Measure	Vitamin C Infusion (Ascorbic Acid) n=6 Participants Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours	Placebo n=6 Participants Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours
Changes to Urine pH	5.31 units on a scale Standard Deviation 2.01	5.17 units on a scale Standard Deviation 0.41

SECONDARY outcome

Timeframe: Baseline and 96 hours

Urine samples are collected to check for the presence of crystalluria (microscopic crystals) that could indicate a risk for kidney stones.

Outcome measures

Measure	Vitamin C Infusion (Ascorbic Acid) n=8 Participants Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours	Placebo n=6 Participants Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours
Changes to Urine Microscopy Number of participants with crystalluria at baseline	0 Participants	0 Participants
Changes to Urine Microscopy Number of patients with crystalluria at Day 4	0 Participants	0 Participants

SECONDARY outcome

Timeframe: up to 168 hours

Documentation of the need for more intensive medical care such as ventilator (breathing machine) or vasopressors (intravenous medications use increase blood pressure) when not needed at baseline

Outcome measures

Measure	Vitamin C Infusion (Ascorbic Acid) n=10 Participants Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours	Placebo n=10 Participants Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours
Changes to Level of Medical Care	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 28

The number of days not spent in an intensive care unit (ICU)

Outcome measures

Measure	Vitamin C Infusion (Ascorbic Acid) n=10 Participants Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours	Placebo n=10 Participants Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours
ICU-free Days	16.40 days Standard Deviation 14.17	13.20 days Standard Deviation 13.06

SECONDARY outcome

Timeframe: Day 28

Any cause of death that is anticipated or unanticipated

Outcome measures

Measure	Vitamin C Infusion (Ascorbic Acid) n=10 Participants Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours	Placebo n=10 Participants Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours
Number of Deaths Due to Any Cause	4 Deaths	3 Deaths

SECONDARY outcome

Timeframe: Day 90

Any cause of death that is anticipated or unanticipated

Outcome measures

Measure	Vitamin C Infusion (Ascorbic Acid) n=10 Participants Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours	Placebo n=10 Participants Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours
Number of Deaths Due to Any Cause	5 Deaths	4 Deaths

SECONDARY outcome

Timeframe: Day 90

The number of days spent outside of the hospital

Outcome measures

Measure	Vitamin C Infusion (Ascorbic Acid) n=5 Participants Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours	Placebo n=8 Participants Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours
Hospital-free Days	58.40 days Standard Deviation 32.91	48.88 days Standard Deviation 33.04

Adverse Events

Vitamin C Infusion (Ascorbic Acid)

Serious events: 2 serious events

Other events: 7 other events

Deaths: 5 deaths

Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 4 deaths

Serious adverse events

Measure	Vitamin C Infusion (Ascorbic Acid) n=10 participants at risk Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours	Placebo n=10 participants at risk Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours
General disorders Weakness, hospitalization	10.0% 1/10 • Number of events 1 • Up to 90 days after drug infusion	0.00% 0/10 • Up to 90 days after drug infusion
Renal and urinary disorders Acute kidney injury	10.0% 1/10 • Number of events 1 • Up to 90 days after drug infusion	0.00% 0/10 • Up to 90 days after drug infusion

Other adverse events

Measure	Vitamin C Infusion (Ascorbic Acid) n=10 participants at risk Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours	Placebo n=10 participants at risk Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours
Metabolism and nutrition disorders Hypokalemia	10.0% 1/10 • Number of events 1 • Up to 90 days after drug infusion	30.0% 3/10 • Number of events 3 • Up to 90 days after drug infusion
Gastrointestinal disorders Abdominal pain	10.0% 1/10 • Number of events 1 • Up to 90 days after drug infusion	0.00% 0/10 • Up to 90 days after drug infusion
Renal and urinary disorders Bladder spasm	0.00% 0/10 • Up to 90 days after drug infusion	10.0% 1/10 • Number of events 1 • Up to 90 days after drug infusion
Vascular disorders Deep vein thrombosis	10.0% 1/10 • Number of events 1 • Up to 90 days after drug infusion	0.00% 0/10 • Up to 90 days after drug infusion
Investigations Electrocardiogram QT corrected interval	10.0% 1/10 • Number of events 1 • Up to 90 days after drug infusion	0.00% 0/10 • Up to 90 days after drug infusion
Metabolism and nutrition disorders Hyperglycemia	10.0% 1/10 • Number of events 1 • Up to 90 days after drug infusion	20.0% 2/10 • Number of events 2 • Up to 90 days after drug infusion
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/10 • Up to 90 days after drug infusion	10.0% 1/10 • Number of events 1 • Up to 90 days after drug infusion
Metabolism and nutrition disorders Hypomagnesemia	10.0% 1/10 • Number of events 1 • Up to 90 days after drug infusion	0.00% 0/10 • Up to 90 days after drug infusion
Metabolism and nutrition disorders Hypophospahtemia	10.0% 1/10 • Number of events 1 • Up to 90 days after drug infusion	40.0% 4/10 • Number of events 4 • Up to 90 days after drug infusion
Cardiac disorders Hypotension	0.00% 0/10 • Up to 90 days after drug infusion	10.0% 1/10 • Number of events 1 • Up to 90 days after drug infusion
Investigations QT interval prolonged	10.0% 1/10 • Number of events 1 • Up to 90 days after drug infusion	0.00% 0/10 • Up to 90 days after drug infusion
Gastrointestinal disorders Vomiting	10.0% 1/10 • Number of events 1 • Up to 90 days after drug infusion	0.00% 0/10 • Up to 90 days after drug infusion

Additional Information

Arun J Sanyal, MD

Virginia Commonwealth University

Phone: 804-828-4060

Email: arun.sanyal@vcuhealth.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place