Back to resultsVitamin C Infusion for TReatment in Sepsis and Alcoholic Hepatitis (CITRIS-AH)
Primary Purpose
Alcoholic Hepatitis, Sepsis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Vitamin C
Dextrose 5% in water
Sponsored by
About this trial
This is an interventional treatment trial for Alcoholic Hepatitis
Eligibility Criteria
Inclusion Criteria:
Alcoholic Hepatitis diagnosed by one of the following methods:
- liver biopsy
- clinical diagnosis based on history of alcohol use, presence of jaundice (yellowing of skin), blood tests indicating liver injury, and absence of other causes of liver injury (autoimmune disease, viral hepatitis, drug toxicity)
- Suspected or proven infection
- Presence of systemic inflammatory response to infection (fever, hypothermia (low temperature), tachycardia (fast heart rate), leukocytosis (high white blood cell count), leukopenia (low white blood cell count), high respiratory (breathing) rate, or need for mechanical ventilation (a machine to assist in breathing).
Presence of organ failure due to the body's response to infection indicated by any of the following:
- Hypotension (low blood pressure) or need for medications to raise blood pressure
- Arterial hypoxemia (low blood oxygen) or need for high flow of oxygen
- High lactate level (blood test indicating active response to infection)
- Low urine output despite administration of intravenous fluids
- Low platelet count (blood test)
- Coagulopathy (decreased blood clotting ability based on a blood test)
- High bilirubin (blood test)
- Mental status changes (confusion or delirium)
- Absence of drugs present on urine or blood tests that indicate the possibility of liver damage or mental status changes from other causes
Exclusion Criteria:
- Allergy to Vitamin C
- Unable to provide consent
- Age less than 18 years
- No intravenous access (IV line) in a patient needing glucose (blood sugar) checks more than twice daily
- Presence of diabetic ketoacidosis (a serious complication of diabetes)
- Inability of patient, legally authorized representative and/or physician to commit to full medical support
- Pregnancy or breast feeding
- Life expectancy less than 24 hours
- Active or history of kidney stone
- History of chronic kidney disease
- History of glucose-6-phosphate deficiency (a low blood protein that can cause red blood cells to break down)
- Active cancer (except non-melanoma skin cancer)
- Uncontrolled gastrointestinal bleeding
- Other causes of liver injury such as viruses, autoimmune disease, drug toxicity
- History of severe liver cirrhosis complications including variceal bleeding within the last 3 months, large ascites (fluid accumulation in the abdomen) or hepatocellular carcinoma (liver cancer)
- History of organ transplantation
- Initial AST or ALT (blood test indicating a liver problem)
- Presence of acetaminophen or other drugs on urine or blood toxicology test
- Non-English speaking
- Prisoner or other ward of the state
Sites / Locations
- Virginia Commonwealth University
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Vitamin C infusion (ascorbic acid)
Placebo
Arm Description
Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)
Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours
Outcomes
Primary Outcome Measures
Change in Model for End Stage Liver Disease (MELD) Score
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).
Secondary Outcome Measures
Change in Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) Score
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)
Change in Aspartate Aminotransferase (AST) Level
Standard blood test used to determine the severity and nature of liver problems.
Change in Alanine Aminotransferase (ALT) Level
Standard blood test used to determine the severity and nature of liver problems.
Change in Total Bilirubin
Standard blood test used to determine the severity and nature of liver problems.
Change in Alkaline Phosphatase
Standard blood test used to determine the severity and nature of liver problems.
Change in Albumin
Standard blood test used to determine the severity and nature of liver problems.
Number of Treatment-related Adverse Events as Assessed by CTCAE v5.0
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)
Changes to Corrected QT Interval (QTc)
An electrocardiogram (ECG or test of the electrical activity of the heart) is performed to determine if there are changes to the heart rhythm.
Changes to Urine pH
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.
Changes to Urine Microscopy
Urine samples are collected to check for the presence of crystalluria (microscopic crystals) that could indicate a risk for kidney stones.
Changes to Level of Medical Care
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
ICU-free Days
The number of days not spent in an intensive care unit (ICU)
Number of Deaths Due to Any Cause
Any cause of death that is anticipated or unanticipated
Number of Deaths Due to Any Cause
Any cause of death that is anticipated or unanticipated
Hospital-free Days
The number of days spent outside of the hospital
Full Information
NCT ID
NCT03829683
First Posted
January 17, 2019
Last Updated
August 25, 2023
Sponsor
Virginia Commonwealth University
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
1. Study Identification
Unique Protocol Identification Number
NCT03829683
Brief Title
Vitamin C Infusion for TReatment in Sepsis and Alcoholic Hepatitis
Acronym
CITRIS-AH
Official Title
Vitamin C Infusion for TReatment in Sepsis and Alcoholic Hepatitis
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
April 16, 2019 (Actual)
Primary Completion Date
March 31, 2022 (Actual)
Study Completion Date
June 23, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Virginia Commonwealth University
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this research study is to test the safety, tolerability, and effectiveness of Vitamin C (ascorbic acid) intravenous infusion when used to treat alcoholic hepatitis (inflammation of the liver from heavy alcohol use) and sepsis (life-threatening complication of an infection).
Detailed Description
Alcoholic hepatitis is inflammation of the liver due to alcohol consumption. It can cause one or more of the following symptoms such as jaundice (yellow discoloration of the eyes and skin), pain on the right side of the abdomen, and is accompanied by an enlarged liver. Sepsis is a life-threatening complication of an infection. As the body tries to fight an infection it sends chemicals into the bloodstream. These chemicals that are trying to fight the infection can cause inflammation. This inflammation can cause damage to many body systems and make them fail. Patients with alcoholic hepatitis and sepsis have low levels of Vitamin C in the bloodstream. Vitamin C has been shown to reduce inflammation and organ dysfunction in patients with severe infections.
The investigators do not yet know if Vitamin C will be effective in alcoholic hepatitis. Taking Vitamin C by mouth is not effective as a treatment in people with this condition so participants will receive the Vitamin C intravenously (IV). Participants will be randomly assigned to receive either Vitamin C or a placebo given through an IV every six hours for four days.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcoholic Hepatitis, Sepsis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Study drug will be double-blind with matching placebo. Vitamin C 200mg/kg/24hours or placebo (Dextrose 5% in water) will be given intravenously every 6 hours for up to 96 hours of treatment.
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Vitamin C infusion (ascorbic acid)
Arm Type
Active Comparator
Arm Description
Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours
Intervention Type
Drug
Intervention Name(s)
Vitamin C
Other Intervention Name(s)
ascorbic acid, AscA, Ascor
Intervention Description
200mg/kg/24hours
Intervention Type
Drug
Intervention Name(s)
Dextrose 5% in water
Other Intervention Name(s)
D5W
Intervention Description
50mL intravenously every 6 hours
Primary Outcome Measure Information:
Title
Change in Model for End Stage Liver Disease (MELD) Score
Description
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).
Time Frame
Baseline and 96 hours
Secondary Outcome Measure Information:
Title
Change in Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) Score
Description
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)
Time Frame
Baseline and 96 hours
Title
Change in Aspartate Aminotransferase (AST) Level
Description
Standard blood test used to determine the severity and nature of liver problems.
Time Frame
Baseline and 96 hours
Title
Change in Alanine Aminotransferase (ALT) Level
Description
Standard blood test used to determine the severity and nature of liver problems.
Time Frame
Baseline and 96 hours
Title
Change in Total Bilirubin
Description
Standard blood test used to determine the severity and nature of liver problems.
Time Frame
Baseline and 96 hours
Title
Change in Alkaline Phosphatase
Description
Standard blood test used to determine the severity and nature of liver problems.
Time Frame
Baseline and 96 hours
Title
Change in Albumin
Description
Standard blood test used to determine the severity and nature of liver problems.
Time Frame
Baseline and 96 hours
Title
Number of Treatment-related Adverse Events as Assessed by CTCAE v5.0
Description
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)
Time Frame
up to 96 hours
Title
Changes to Corrected QT Interval (QTc)
Description
An electrocardiogram (ECG or test of the electrical activity of the heart) is performed to determine if there are changes to the heart rhythm.
Time Frame
Baseline and 96 hours
Title
Changes to Urine pH
Description
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.
Time Frame
Baseline and 96 hours
Title
Changes to Urine Microscopy
Description
Urine samples are collected to check for the presence of crystalluria (microscopic crystals) that could indicate a risk for kidney stones.
Time Frame
Baseline and 96 hours
Title
Changes to Level of Medical Care
Description
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
Time Frame
up to 168 hours
Title
ICU-free Days
Description
The number of days not spent in an intensive care unit (ICU)
Time Frame
Day 28
Title
Number of Deaths Due to Any Cause
Description
Any cause of death that is anticipated or unanticipated
Time Frame
Day 28
Title
Number of Deaths Due to Any Cause
Description
Any cause of death that is anticipated or unanticipated
Time Frame
Day 90
Title
Hospital-free Days
Description
The number of days spent outside of the hospital
Time Frame
Day 90
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Alcoholic Hepatitis diagnosed by one of the following methods:
liver biopsy
clinical diagnosis based on history of alcohol use, presence of jaundice (yellowing of skin), blood tests indicating liver injury, and absence of other causes of liver injury (autoimmune disease, viral hepatitis, drug toxicity)
Suspected or proven infection
Presence of systemic inflammatory response to infection (fever, hypothermia (low temperature), tachycardia (fast heart rate), leukocytosis (high white blood cell count), leukopenia (low white blood cell count), high respiratory (breathing) rate, or need for mechanical ventilation (a machine to assist in breathing).
Presence of organ failure due to the body's response to infection indicated by any of the following:
Hypotension (low blood pressure) or need for medications to raise blood pressure
Arterial hypoxemia (low blood oxygen) or need for high flow of oxygen
High lactate level (blood test indicating active response to infection)
Low urine output despite administration of intravenous fluids
Low platelet count (blood test)
Coagulopathy (decreased blood clotting ability based on a blood test)
High bilirubin (blood test)
Mental status changes (confusion or delirium)
Absence of drugs present on urine or blood tests that indicate the possibility of liver damage or mental status changes from other causes
Exclusion Criteria:
Allergy to Vitamin C
Unable to provide consent
Age less than 18 years
No intravenous access (IV line) in a patient needing glucose (blood sugar) checks more than twice daily
Presence of diabetic ketoacidosis (a serious complication of diabetes)
Inability of patient, legally authorized representative and/or physician to commit to full medical support
Pregnancy or breast feeding
Life expectancy less than 24 hours
Active or history of kidney stone
History of chronic kidney disease
History of glucose-6-phosphate deficiency (a low blood protein that can cause red blood cells to break down)
Active cancer (except non-melanoma skin cancer)
Uncontrolled gastrointestinal bleeding
Other causes of liver injury such as viruses, autoimmune disease, drug toxicity
History of severe liver cirrhosis complications including variceal bleeding within the last 3 months, large ascites (fluid accumulation in the abdomen) or hepatocellular carcinoma (liver cancer)
History of organ transplantation
Initial AST or ALT (blood test indicating a liver problem)
Presence of acetaminophen or other drugs on urine or blood toxicology test
Non-English speaking
Prisoner or other ward of the state
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arun J Sanyal, MD
Organizational Affiliation
Virginia Commonwealth University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Vitamin C Infusion for TReatment in Sepsis and Alcoholic Hepatitis
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