Alcoholic HepatitisPhase 2CITRIS-AHNCT03829683
Vitamin C Infusion for TReatment in Sepsis and Alcoholic Hepatitis
A Phase 2 study testing Vitamin C and Dextrose 5% in water in people with Alcoholic Hepatitis and Sepsis, run by Virginia Commonwealth University at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Alcoholic Hepatitis, Sepsis
- What is being tested?
- Vitamin C and Dextrose 5% in water
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Apr 2019to 23 Jun 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Virginia Commonwealth University
Richmond, Virginia, 23298
About this study
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).
Read the 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.
- Conditions
- Alcoholic Hepatitis, Sepsis
- Being tested
- Vitamin C, Dextrose 5% in water
- Medical subject headings
- Hepatitis, Alcoholic, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin CDrug
Also called ascorbic acid, AscA, Ascor
200mg/kg/24hours
Dextrose 5% in waterDrug
Also called D5W
50mL intravenously every 6 hours
| Study group | Role | What they receive |
|---|---|---|
| Vitamin C infusion (ascorbic acid) | Active comparator | Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Receives: Drug: Vitamin C; Drug: Dextrose 5% in water |
| Placebo | Placebo comparator | Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Receives: Drug: Dextrose 5% in water |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline and 96 hours
Secondary outcomes (15)
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)
Measured: Baseline and 96 hours
Change in Aspartate Aminotransferase (AST) Level
Standard blood test used to determine the severity and nature of liver problems.
Measured: Baseline and 96 hours
Change in Alanine Aminotransferase (ALT) Level
Standard blood test used to determine the severity and nature of liver problems.
Measured: Baseline and 96 hours
Change in Total Bilirubin
Standard blood test used to determine the severity and nature of liver problems.
Measured: Baseline and 96 hours
Change in Alkaline Phosphatase
Standard blood test used to determine the severity and nature of liver problems.
Measured: Baseline and 96 hours
Change in Albumin
Standard blood test used to determine the severity and nature of liver problems.
Measured: Baseline and 96 hours
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)
Measured: up to 96 hours
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.
Measured: Baseline and 96 hours
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.
Measured: Baseline and 96 hours
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.
Measured: Baseline and 96 hours
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
Measured: up to 168 hours
ICU-free Days
The number of days not spent in an intensive care unit (ICU)
Measured: Day 28
Number of Deaths Due to Any Cause
Any cause of death that is anticipated or unanticipated
Measured: Day 28
Number of Deaths Due to Any Cause
Any cause of death that is anticipated or unanticipated
Measured: Day 90
Hospital-free Days
The number of days spent outside of the hospital
Measured: Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2019
- Study start16 Apr 2019
- Primary completion31 Mar 2022
- Study completion23 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alcoholic HepatitisStudies of the same condition, open and under way.
- More trials run by Virginia Commonwealth UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Sponsor
- Investigators
- Arun J Sanyal, MD, Principal investigator, Virginia Commonwealth University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03829683
- Sponsor's protocol ID
- HM20014364
- Other IDs
- U01AA026966
- Acronym
- CITRIS-AH
- Status last verified
- Aug 2023
- First submitted
- 17 Jan 2019
- Last updated
- 28 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vitamin C Infusion for TReatment in Sepsis and Alcoholic Hepatitis
- ClinicalTrials.gov ID
- NCT03829683
- Acronym / sponsor ID
- CITRIS-AH / HM20014364
- Conditions
- Alcoholic Hepatitis, Sepsis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- 16 Apr 2019 (actual)
- Primary completion
- 31 Mar 2022 (actual)
- Study completion
- 23 Jun 2022 (actual)
- First posted
- 4 Feb 2019 (actual)
- Results
- Posted 21 Mar 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vitamin C infusion (ascorbic acid) | Active comparator | Drug: Vitamin C, Drug: Dextrose 5% in waterVitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) |
| Placebo | Placebo comparator | Drug: Dextrose 5% in waterDextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Alcoholic Hepatitis diagnosed by one of the following methods:
- 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:
- Absence of drugs present on urine or blood tests that indicate the possibility of liver damage or mental status changes from other causes
Key exclusion criteria (20 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin CAlso: ascorbic acid, AscA, Ascor200mg/kg/24hours | Drug | Vitamin C infusion (ascorbic acid) |
| Dextrose 5% in waterAlso: D5W50mL intravenously every 6 hours | Drug | Placebo, Vitamin C infusion (ascorbic acid) |
Primary outcome
Change in Model for End Stage Liver Disease (MELD) Score
Time frame: Baseline and 96 hours
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).
15 secondary outcomes
Change in Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) Score
Time frame: Baseline and 96 hours
Change in Aspartate Aminotransferase (AST) Level
Time frame: Baseline and 96 hours
Change in Alanine Aminotransferase (ALT) Level
Time frame: Baseline and 96 hours
Change in Total Bilirubin
Time frame: Baseline and 96 hours
Change in Alkaline Phosphatase
Time frame: Baseline and 96 hours
Change in Albumin
Time frame: Baseline and 96 hours
Number of Treatment-related Adverse Events as Assessed by CTCAE v5.0
Time frame: up to 96 hours
Changes to Corrected QT Interval (QTc)
Time frame: Baseline and 96 hours
Changes to Urine pH
Time frame: Baseline and 96 hours
Changes to Urine Microscopy
Time frame: Baseline and 96 hours
Changes to Level of Medical Care
Time frame: up to 168 hours
ICU-free Days
Time frame: Day 28
Number of Deaths Due to Any Cause
Time frame: Day 28
Number of Deaths Due to Any Cause
Time frame: Day 90
Hospital-free Days
Time frame: Day 90
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arun J Sanyal, MD principal investigator
Virginia Commonwealth University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vitamin C and Dextrose 5% in water in people with Alcoholic Hepatitis and Sepsis, run by Virginia Commonwealth University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Model for End Stage Liver Disease (MELD) Score (time frame: Baseline and 96 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2023.