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

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ClinicalTrials.gov Identifier: NCT03829683
Recruitment Status : Not yet recruiting
First Posted : February 4, 2019
Last Update Posted : March 15, 2019
Sponsor:
Collaborator:
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Information provided by (Responsible Party):
Virginia Commonwealth University

Tracking Information
First Submitted Date  ICMJE January 17, 2019
First Posted Date  ICMJE February 4, 2019
Last Update Posted Date March 15, 2019
Estimated Study Start Date  ICMJE April 2019
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 1, 2019)
Change in Model for End Stage Liver Disease (MELD) score [ Time Frame: 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).
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03829683 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 1, 2019)
  • Change in Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) Score [ Time Frame: 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 [ Time Frame: Baseline and 96 hours ]
    Standard blood test used to determine the severity and nature of liver problems.
  • Change in alanine aminotransferase (ALT) level [ Time Frame: Baseline and 96 hours ]
    Standard blood test used to determine the severity and nature of liver problems.
  • Change in total bilirubin [ Time Frame: Baseline and 96 hours ]
    Standard blood test used to determine the severity and nature of liver problems.
  • Change in alkaline phosphatase [ Time Frame: Baseline and 96 hours ]
    Standard blood test used to determine the severity and nature of liver problems.
  • Change in albumin [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Day 28 ]
    The number of days not spent in an intensive care unit (ICU)
  • Number of deaths due to any cause [ Time Frame: Day 28 ]
    Any cause of death that is anticipated or unanticipated
  • Number of deaths due to any cause [ Time Frame: Day 90 ]
    Any cause of death that is anticipated or unanticipated
  • Hospital-free days [ Time Frame: Day 90 ]
    The number of days spent outside of the hospital
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vitamin C Infusion for TReatment in Sepsis and Alcoholic Hepatitis
Official Title  ICMJE Vitamin C Infusion for TReatment in Sepsis and Alcoholic Hepatitis
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE
  • Alcoholic Hepatitis
  • Sepsis
Intervention  ICMJE
  • Drug: Vitamin C
    200mg/kg/24hours
    Other Names:
    • ascorbic acid
    • AscA
    • Ascor
  • Drug: Dextrose 5% in water
    50mL intravenously every 6 hours
    Other Name: D5W
Study Arms  ICMJE
  • Active Comparator: Vitamin C infusion (ascorbic acid)
    Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)
    Interventions:
    • Drug: Vitamin C
    • Drug: Dextrose 5% in water
  • Placebo Comparator: Placebo
    Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours
    Intervention: Drug: Dextrose 5% in water
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: February 1, 2019)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2021
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Stephanie Taylor, RN MSN 804-828-9311 stephanie.taylor@vcuhealth.org
Contact: Rebecca Collen, BSN 804-628-4376 rebecca.collen@vcuhealth.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03829683
Other Study ID Numbers  ICMJE HM20014364
U01AA026966 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Virginia Commonwealth University
Study Sponsor  ICMJE Virginia Commonwealth University
Collaborators  ICMJE National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Investigators  ICMJE
Principal Investigator: Arun J Sanyal, MD Virginia Commonwealth University
PRS Account Virginia Commonwealth University
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP