Vitamin C Infusion for TReatment in Sepsis and Alcoholic Hepatitis
Keywords
Abstract
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.
Dates
| Last Verified: | 05/31/2020 |
| First Submitted: | 01/16/2019 |
| Estimated Enrollment Submitted: | 01/31/2019 |
| First Posted: | 02/03/2019 |
| Last Update Submitted: | 05/31/2020 |
| Last Update Posted: | 06/03/2020 |
| Actual Study Start Date: | 04/15/2019 |
| Estimated Primary Completion Date: | 01/31/2021 |
| Estimated Study Completion Date: | 04/30/2021 |
Condition or disease
Intervention/treatment
Drug: Vitamin C infusion (ascorbic acid)
Drug: Dextrose 5% in water
Phase
Arm Groups
| 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 infusion (ascorbic acid) 200mg/kg/24hours |
| Placebo Comparator: Placebo Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| 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 |
Outcome
Primary Outcome Measures
1. Change in Model for End Stage Liver Disease (MELD) score [Baseline and 96 hours]
Secondary Outcome Measures
1. Change in Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) Score [Baseline and 96 hours]
2. Change in aspartate aminotransferase (AST) level [Baseline and 96 hours]
3. Change in alanine aminotransferase (ALT) level [Baseline and 96 hours]
4. Change in total bilirubin [Baseline and 96 hours]
5. Change in alkaline phosphatase [Baseline and 96 hours]
6. Change in albumin [Baseline and 96 hours]
7. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [up to 96 hours]
8. Changes to corrected QT interval (QTc) [Baseline and 96 hours]
9. Changes to urine pH [Baseline and 96 hours]
10. Changes to urine microscopy [Baseline and 96 hours]
11. Changes to Level of Medical Care [up to 168 hours]
12. ICU-free days [Day 28]
13. Number of deaths due to any cause [Day 28]
14. Number of deaths due to any cause [Day 90]
15. Hospital-free days [Day 90]
