Liver CirrhosisNCT04494451
Efficacy of Vitamin C on AKI Outcomes in Critically Ill Cirrhotics With Multidrug-resistant Bacterial Infections.
A study testing Vit C and Standard medical Treatment in people with Liver Cirrhosis, run by Institute of Liver and Biliary Sciences, India at 1 site in India.
Trial summary
In this prospective randomized controlled trial we aim to evaluate the impact of vitamin C on AKI outcomes in patients with cirrhosis and MDR infections. We also aim to evaluate the effects of iv vitamin c on systemic hemodynamics (cardiac output and systemic vascular resistive index, extravascular lung water and lung… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Liver Cirrhosis
- What is being tested?
- Vit C and Standard medical Treatment
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteIndia
- Study dates
- 15 Sep 2021to 2 Nov 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Critically ill cirrhotics with MDR infections
Who cannot join
- Patients with age less than 18 years
- Known severe cardiopulmonary disease (structural or valvular heart disease, coronary artery disease, COPD)
- Patients in DIC with platelets < 20,000 and INR > 4 or active bleeding
- Limitations of care (defined as refusal of cardiovascular and respiratory support modes) including "do not intubate" (DNI) status
- Current hospitalization > 15 days for patients with nosocomial acquisition of MDR at time of randomization
- Known allergy or contraindication to vitamin C (including previously or currently diagnosed primary hyperoxaluria and/or oxalate nephropathy, or known/suspected ethylene glycol ingestion,
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- Known glucose-6-phosphate dehydrogenase (G6PD) deficiency)
- Use of vitamin C at a dose of > 1 gram daily within the 24 hours preceding first episode of qualifying organ dysfunction during a given ED or ICU admission
- Patients with HCC (beyond Milan) or extrahepatic malignancies
- Patients with HVOTO or EHPVO
- Pregnancy or active breastfeeding
- Current participation in another interventional research study
- Active or history of kidney stone
- History of chronic kidney disease or intrinsic kidney disease
- Patients already on maintenance hemodialysis prior to presentation
- Patients with refractory septic shock or hypoxemia (Pa02/Fio2 ratio <100)
- Extremely moribund patients with an expected life expectancy of less than 24 hours
- Failure to provide informed consent
- Patients with retroviral infection
- Patients with acute on chronic liver failure (APASL definition)
- Patients with urinary tract infection
Trial locations and contacts
1 site in 1 country.
India1 site
Institute of Liver & Biliary Sciences
New Delhi, National Capital Territory of Delhi, 110070
About this study
Official title: Efficacy of Vitamin C on AKI Outcomes in Critically Ill Cirrhotics With Multidrug-resistant Bacterial Infections- A Randomized Controlled Trial
In this prospective randomized controlled trial we aim to evaluate the impact of vitamin C on AKI outcomes in patients with cirrhosis and MDR infections. We also aim to evaluate the effects of iv vitamin c on systemic hemodynamics (cardiac output and systemic vascular resistive index, extravascular lung water and lung permeability index), endothelial function and coagulation, microcirculation (as assessed by lactate clearance and central venous oxygen saturation), mitochondrial function, 28-day mortality and vasopressor, ventilator and RRT free days in the ICU. The safety and side-effects of vitamin c would also be evaluated.
Patients with suspected (nosocomial acquisition) or proven MDR infections would be screened and randomized to two groups who meet the inclusion and exclusion criteria.
Group 1: Will receive iv vitamin C (25 mg/kg or max. 1.5 gram every 6 hourly) for maximum 5 days along with iv antibiotics as per institutional protocol Group 2: iv antibiotics alone
Read the detailed description
Aim \& Objectives Primary To evaluate the impact of vitamin C on AKI outcomes in patients with cirrhosis and MDR infections
Secondary Objectives To assess the effects on systemic hemodynamics (cardiac output and systemic vascular resistive index, extravascular lung water and lung permeability index) Impact of Vitamin C on endothelial function and coagulation Improvement in microcirculation as assessed by lactate clearance and central venous oxygen saturation To assess the effects on 28-day mortality. Improvement in SOFA scores in both groups Vasopressor, ventilator and RRT free days in the ICU Incidence of adverse effects in both groups Prevalence of vitamin C deficiency in cirrhotics with sepsis and impact of exogenous vitamin C in improving endogenous levels of ascorbate and norepinephrine levels Impact of vitamin C on oxidative stress by evaluation of mitochondrial bioenergetics
(B) Methodology Patients with suspected (nosocomial acquisition) or proven MDR infections would be screened and randomized to two groups as under Group 1: Will receive iv vitamin C (25 mg/kg or max. 1.5 gram every 6 hourly) for maximum 5 days along with iv antibiotics as per institutional protocol Group 2: iv antibiotics alone All patients with nosocomial bacterial infections or septic shock would be screened for randomization would be considered for enrolment in the trial. Nosocomial infection would be defined as infections developing after 48 hours of hospitalization. Following this, patients meeting the inclusion and exclusion criteria will be screened and randomized to the two treatment groups. Standard of care for management of antibiotics, fluids and vasopressors would be as per institutional guidelines. At baseline, blood and urine sample would be stored for all patients for performing mitochondrial bioenergetics, endotoxin, proinflammatory cytokines (IL-6, IL-IB, TNF-alpha, MCP-1, IL-1O) and urine biomarkers (urine NGAL and cystatin C) and markers of endothelial dysfunction(von willebrand factor and ADAMTS). Following randomization patients would be allocated to receive intravenous vitamin C (1.5 g every 6 h or 25 mg/kg for 5 days) along with intravenous antibiotics
Study Population:
Patients with cirrhosis with MDR infections (nosocomial acquisition) or culture-proven
Study Design:
- A randomized controlled study.
- The study will be conducted on patients admitted to Department of Hepatology from June 2020 to December 2020 at ILBS, New Delhi
- Study group will comprise of patients critically ill cirrhotics with suspected or proven MDR infections
Study period
- The study will be conducted on patients admitted to Department of Hepatology from June 2020 to December 2020 at ILBS, New Delhi
- Study group will comprise of patients critically ill cirrhotics with MDR infections.
Sample Size calculation: Currently there are lack of studies investigating the incidence and outcomes of AKI in this context. The study will be designed as a pilot RCT with an aim to enrol 50 patients in each group.
The detailed cytokine profile, endotoxin assay, markers of endothelial dysfunction and bioenergetics would be performed in a subset of 15 patients in each group.
Intervention: IV Vitamin C
Monitoring and Assessment: Hourly till the patient is in the intensive care unit then every 7 days for 1 month
Statistical analysis
- All variables shall be expressed in mean (sd) or median (range)
- Variables will be compared by Mann- Whitney U test
- For Categorical variables we will use Chi-Square or Fisher's test
- Survival analysis will be done using Cox-proportional regression analysis
Actuarial probability of survival shall be calculated by Kaplan- Meier graph and compared by log- rank test.
Adverse Effects: Any allergic reactions, drop in hemoglobin or development of kidney stones
Stopping rule of the study: Any untoward adverse effects of the intervention.
Ethical issues in the study and plans to address these issue The study is designed to demonstrate the efficacy of intravenous vitamin C in improving AKI outcomes in cirrhotics with MDR infections. Vitamin C is been routinely used in this indication with no major adverse effects. However, head-to-head comparison is needed to identify the evidence and benefits of using this drug in this indication. Only minor side effects like nausea, diarrhea, abdominal bloating, cramps and precipitation of kidney stones have been observed with the drug.
- Conditions
- Liver Cirrhosis
- Being tested
- Vit C, Standard medical Treatment
- Medical subject headings
- Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vit CDrug
vitamin C (25 mg/kg or max. 1.5 gram every 6 hourly) for maximum 5 day
Standard medical TreatmentDrug
iv antibiotics alone
| Study group | Role | What they receive |
|---|---|---|
| Vitamin C + Standard Medical Treatment | Experimental | vitamin C (25 mg/kg or max. 1.5 gram every 6 hourly) for maximum 5 days along with iv antibiotics as per institutional protocol along with iv antibiotics Receives: Drug: Vit C; Drug: Standard medical Treatment |
| Standard Medical Treatment | Active comparator | iv antibiotics alone Receives: Drug: Standard medical Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
AKI progression at day 5
Measured: Day 5
Secondary outcomes (5)
Mortality in both groups
Measured: Day 28
Time to reversal of AKI in both groups
Measured: Day 14
Lactate clearance in both groups
Measured: 12 hours
Lactate clearance in both groups
Measured: 24 hours
Vasopressor, ventilator and days free of dialysis during ICU stay
Measured: Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2020
- Study start15 Sep 2021
- Primary completion2 Nov 2022
- Study completion2 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver CirrhosisStudies of the same condition, open and under way.
- More trials run by Institute of Liver and Biliary Sciences, IndiaThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute of Liver and Biliary Sciences, India
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04494451
- Sponsor's protocol ID
- ILBS-Cirrhosis-35
- Status last verified
- Oct 2023
- First submitted
- 28 Jul 2020
- Last updated
- 3 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Vitamin C on AKI Outcomes in Critically Ill Cirrhotics With Multidrug-resistant Bacterial Infections- A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04494451
- Acronym / sponsor ID
- ILBS-Cirrhosis-35
- Conditions
- Liver Cirrhosis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Institute of Liver and Biliary Sciences, IndiaUniversity, hospital or other
- Study start
- 15 Sep 2021 (actual)
- Primary completion
- 2 Nov 2022 (actual)
- Study completion
- 2 Nov 2022 (actual)
- First posted
- 31 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this prospective randomized controlled trial we aim to evaluate the impact of vitamin C on AKI outcomes in patients with cirrhosis and MDR infections. We also aim to evaluate the effects of iv vitamin c on systemic hemodynamics (cardiac output and systemic vascular resistive index, extravascular lung water and lung permeability index), endothelial function and coagulation, microcirculation (as assessed by lactate clearance and central venous oxygen saturation), mitochondrial function, 28-day mortality and vasopressor, ventilator and RRT free days in the ICU. The safety and side-effects of vitamin c would also be evaluated.
Patients with suspected (nosocomial acquisition) or proven MDR infections would be screened and randomized to two groups who meet the inclusion and exclusion criteria.
Group 1: Will receive iv vitamin C (25 mg/kg or max. 1.5 gram every 6 hourly) for maximum 5 days along with iv antibiotics as per institutional protocol Group 2: iv antibiotics alone
Detailed description
Aim \& Objectives Primary To evaluate the impact of vitamin C on AKI outcomes in patients with cirrhosis and MDR infections
Secondary Objectives To assess the effects on systemic hemodynamics (cardiac output and systemic vascular resistive index, extravascular lung water and lung permeability index) Impact of Vitamin C on endothelial function and coagulation Improvement in microcirculation as assessed by lactate clearance and central venous oxygen saturation To assess the effects on 28-day mortality. Improvement in SOFA scores in both groups Vasopressor, ventilator and RRT free days in the ICU Incidence of adverse effects in both groups Prevalence of vitamin C deficiency in cirrhotics with sepsis and impact of exogenous vitamin C in improving endogenous levels of ascorbate and norepinephrine levels Impact of vitamin C on oxidative stress by evaluation of mitochondrial bioenergetics
(B) Methodology Patients with suspected (nosocomial acquisition) or proven MDR infections would be screened and randomized to two groups as under Group 1: Will receive iv vitamin C (25 mg/kg or max. 1.5 gram every 6 hourly) for maximum 5 days along with iv antibiotics as per institutional protocol Group 2: iv antibiotics alone All patients with nosocomial bacterial infections or septic shock would be screened for randomization would be considered for enrolment in the trial. Nosocomial infection would be defined as infections developing after 48 hours of hospitalization. Following this, patients meeting the inclusion and exclusion criteria will be screened and randomized to the two treatment groups. Standard of care for management of antibiotics, fluids and vasopressors would be as per institutional guidelines. At baseline, blood and urine sample would be stored for all patients for performing mitochondrial bioenergetics, endotoxin, proinflammatory cytokines (IL-6, IL-IB, TNF-alpha, MCP-1, IL-1O) and urine biomarkers (urine NGAL and cystatin C) and markers of endothelial dysfunction(von willebrand factor and ADAMTS). Following randomization patients would be allocated to receive intravenous vitamin C (1.5 g every 6 h or 25 mg/kg for 5 days) along with intravenous antibiotics
Study Population:
Patients with cirrhosis with MDR infections (nosocomial acquisition) or culture-proven
Study Design:
- A randomized controlled study.
- The study will be conducted on patients admitted to Department of Hepatology from June 2020 to December 2020 at ILBS, New Delhi
- Study group will comprise of patients critically ill cirrhotics with suspected or proven MDR infections
Study period
- The study will be conducted on patients admitted to Department of Hepatology from June 2020 to December 2020 at ILBS, New Delhi
- Study group will comprise of patients critically ill cirrhotics with MDR infections.
Sample Size calculation: Currently there are lack of studies investigating the incidence and outcomes of AKI in this context. The study will be designed as a pilot RCT with an aim to enrol 50 patients in each group.
The detailed cytokine profile, endotoxin assay, markers of endothelial dysfunction and bioenergetics would be performed in a subset of 15 patients in each group.
Intervention: IV Vitamin C
Monitoring and Assessment: Hourly till the patient is in the intensive care unit then every 7 days for 1 month
Statistical analysis
- All variables shall be expressed in mean (sd) or median (range)
- Variables will be compared by Mann- Whitney U test
- For Categorical variables we will use Chi-Square or Fisher's test
- Survival analysis will be done using Cox-proportional regression analysis
Actuarial probability of survival shall be calculated by Kaplan- Meier graph and compared by log- rank test.
Adverse Effects: Any allergic reactions, drop in hemoglobin or development of kidney stones
Stopping rule of the study: Any untoward adverse effects of the intervention.
Ethical issues in the study and plans to address these issue The study is designed to demonstrate the efficacy of intravenous vitamin C in improving AKI outcomes in cirrhotics with MDR infections. Vitamin C is been routinely used in this indication with no major adverse effects. However, head-to-head comparison is needed to identify the evidence and benefits of using this drug in this indication. Only minor side effects like nausea, diarrhea, abdominal bloating, cramps and precipitation of kidney stones have been observed with the drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vitamin C + Standard Medical Treatment | Experimental | Drug: Vit C, Drug: Standard medical Treatmentvitamin C (25 mg/kg or max. 1.5 gram every 6 hourly) for maximum 5 days along with iv antibiotics as per institutional protocol along with iv antibiotics |
| Standard Medical Treatment | Active comparator | Drug: Standard medical Treatmentiv antibiotics alone |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Critically ill cirrhotics with MDR infections
Key exclusion criteria (21 listed)
- Patients with age less than 18 years
- Known severe cardiopulmonary disease (structural or valvular heart disease, coronary artery disease, COPD)
- Patients in DIC with platelets < 20,000 and INR > 4 or active bleeding
- Limitations of care (defined as refusal of cardiovascular and respiratory support modes) including "do not intubate" (DNI) status
- Current hospitalization > 15 days for patients with nosocomial acquisition of MDR at time of randomization
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 |
|---|---|---|
| Vit Cvitamin C (25 mg/kg or max. 1.5 gram every 6 hourly) for maximum 5 day | Drug | Vitamin C + Standard Medical Treatment |
| Standard medical Treatmentiv antibiotics alone | Drug | Standard Medical Treatment, Vitamin C + Standard Medical Treatment |
Primary outcome
AKI progression at day 5
Time frame: Day 5
5 secondary outcomes
Mortality in both groups
Time frame: Day 28
Time to reversal of AKI in both groups
Time frame: Day 14
Lactate clearance in both groups
Time frame: 12 hours
Lactate clearance in both groups
Time frame: 24 hours
Vasopressor, ventilator and days free of dialysis during ICU stay
Time frame: Day 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2023.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vit C and Standard medical Treatment in people with Liver Cirrhosis, run by Institute of Liver and Biliary Sciences, India at 1 site in India.
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 1 inclusion and 21 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 3 Nov 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 India. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
AKI progression at day 5 (time frame: Day 5). 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 3 Nov 2023; AzTrials last refreshed its copy on 8 Nov 2026.