Clinical trial NCT03829683: Vitamin C Infusion for TReatment in Sepsis and Alcoholic Hepatitis
Official title: Vitamin C Infusion for TReatment in Sepsis and Alcoholic Hepatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alcoholic Hepatitis
Sepsis
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2019-02-04
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Alcoholic Hepatitis diagnosed by one of the following methods:

   1. liver biopsy
   2. 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)
2. Suspected or proven infection
3. 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).
4. Presence of organ failure due to the body's response to infection indicated by any of the following:

   1. Hypotension (low blood pressure) or need for medications to raise blood pressure
   2. Arterial hypoxemia (low blood oxygen) or need for high flow of oxygen
   3. High lactate level (blood test indicating active response to infection)
   4. Low urine output despite administration of intravenous fluids
   5. Low platelet count (blood test)
   6. Coagulopathy (decreased blood clotting ability based on a blood test)
   7. High bilirubin (blood test)
   8. Mental status changes (confusion or delirium)
5. 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:

1. Allergy to Vitamin C
2. Unable to provide consent
3. Age less than 18 years
4. No intravenous access (IV line) in a patient needing glucose (blood sugar) checks more than twice daily
5. Presence of diabetic ketoacidosis (a serious complication of diabetes)
6. Inability of patient, legally authorized representative and/or physician to commit to full medical support
7. Pregnancy or breast feeding
8. Life expectancy less than 24 hours
9. Active or history of kidney stone
10. History of chronic kidney disease
11. History of glucose-6-phosphate deficiency (a low blood protein that can cause red blood cells to break down)
12. Active cancer (except non-melanoma skin cancer)
13. Uncontrolled gastrointestinal bleeding
14. Other causes of liver injury such as viruses, autoimmune disease, drug toxicity
15. 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)
16. History of organ transplantation
17. Initial AST or ALT (blood test indicating a liver problem)
18. Presence of acetaminophen or other drugs on urine or blood toxicology test
19. Non-English speaking
20. Prisoner or other ward of the state

Primary outcomes:
measure: Change in Model for End Stage Liver Disease (MELD) Score
timeFrame: Baseline and 96 hours
Secondary outcomes:
measure: Change in Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) Score
timeFrame: Baseline and 96 hours
measure: Change in Aspartate Aminotransferase (AST) Level
timeFrame: Baseline and 96 hours
measure: Change in Alanine Aminotransferase (ALT) Level
timeFrame: Baseline and 96 hours
measure: Change in Total Bilirubin
timeFrame: Baseline and 96 hours
measure: Change in Alkaline Phosphatase
timeFrame: Baseline and 96 hours
measure: Change in Albumin
timeFrame: Baseline and 96 hours
measure: Number of Treatment-related Adverse Events as Assessed by CTCAE v5.0
timeFrame: up to 96 hours
measure: Changes to Corrected QT Interval (QTc)
timeFrame: Baseline and 96 hours
measure: Changes to Urine pH
timeFrame: Baseline and 96 hours
measure: Changes to Urine Microscopy
timeFrame: Baseline and 96 hours
measure: Changes to Level of Medical Care
timeFrame: up to 168 hours
measure: ICU-free Days
timeFrame: Day 28
measure: Number of Deaths Due to Any Cause
timeFrame: Day 28
measure: Number of Deaths Due to Any Cause
timeFrame: Day 90
measure: Hospital-free Days
timeFrame: Day 90
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Arun J Sanyal, MD
role: PRINCIPAL_INVESTIGATOR
References: