CITRIS-AH: Vitamin C Infusion for TReatment in Sepsis and Alcoholic Hepatitis

Sponsor

Virginia Commonwealth University (Other)

Overall Status

Completed

CT.gov ID

NCT03829683

Collaborator

National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)

Enrollment

Location

Arms

38.2

Actual Duration (Months)

0.5

Patients Per Site Per Month

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Alcoholic Hepatitis Sepsis	Drug: Vitamin C Drug: Dextrose 5% in water	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes 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.

Primary Purpose:

Treatment

Official Title:

Vitamin C Infusion for TReatment in Sepsis and Alcoholic Hepatitis

Actual Study Start Date :

Apr 16, 2019

Actual Primary Completion Date :

Mar 31, 2022

Actual Study Completion Date :

Jun 23, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Vitamin C infusion (ascorbic acid) Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)	Drug: Vitamin C 200mg/kg/24hours Other Names: ascorbic acid AscA Ascor Drug: Dextrose 5% in water 50mL intravenously every 6 hours Other Names: D5W
Placebo Comparator: Placebo Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours	Drug: Dextrose 5% in water 50mL intravenously every 6 hours Other Names: D5W

Arm

Intervention/Treatment

Active Comparator: Vitamin C infusion (ascorbic acid)

Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)

Drug: Vitamin C

200mg/kg/24hours

Other Names:

ascorbic acid

AscA

Ascor

Drug: Dextrose 5% in water

50mL intravenously every 6 hours

Other Names:

D5W

Placebo Comparator: Placebo

Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours

Drug: Dextrose 5% in water

50mL intravenously every 6 hours

Other Names:

D5W

Outcome Measures

Primary Outcome Measures

Change in Model for End Stage Liver Disease (MELD) score [Baseline and 96 hours]
A number that 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 [Baseline and 96 hours]
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 [Baseline and 96 hours]
Standard blood test used to determine the severity and nature of liver problems.
Change in alanine aminotransferase (ALT) level [Baseline and 96 hours]
Standard blood test used to determine the severity and nature of liver problems.
Change in total bilirubin [Baseline and 96 hours]
Standard blood test used to determine the severity and nature of liver problems.
Change in alkaline phosphatase [Baseline and 96 hours]
Standard blood test used to determine the severity and nature of liver problems.
Change in albumin [Baseline and 96 hours]
Standard blood test used to determine the severity and nature of liver problems.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [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)
Changes to corrected QT interval (QTc) [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.
Changes to urine pH [Baseline and 96 hours]
Urine samples are collected to determine changes in pH (acidity) that could indicate a risk for kidney stones.
Changes to urine microscopy [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.
Changes to Level of Medical Care [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
ICU-free days [Day 28]
The number of days not spent in an intensive care unit (ICU)
Number of deaths due to any cause [Day 28]
Any cause of death that is anticipated or unanticipated
Number of deaths due to any cause [Day 90]
Any cause of death that is anticipated or unanticipated
Hospital-free days [Day 90]
The number of days spent outside of the hospital

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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