Vitamin C for Acute Kidney Injury in ACLF With Septic Shock: A Randomized Controlled Trial

Official title

A Randomized Controlled Trial Open Label Evaluating the Efficacy of Vitamin C in Improving Outcomes of Acute Kidney Injury in Patients With ACLF With Septic Shock

Overview

This study is testing whether Vitamin C can help improve kidney function and survival in very sick patients with liver disease. Patients with acute-on-chronic liver failure (ACLF) often develop serious infections that can lead to septic shock and kidney injury, which are major causes of death. In this randomized controlled trial, patients with ACLF and septic shock will be assigned to receive either: 1. Standard medical treatment alone, or 2. Standard medical treatment plus intravenous Vitamin C. Vitamin C is a safe, inexpensive antioxidant that may reduce inflammation, improve circulation, and protect the kidneys. The study will compare how well patients recover from septic shock and kidney injury in the two groups. Blood and urine samples will also be collected to look for biological markers that can predict outcomes.

Detailed description

Acute-on-chronic liver failure (ACLF) is a severe condition in which patients with chronic liver disease suddenly develop liver failure, often triggered by infection. Many of these patients progress to septic shock, and acute kidney injury (AKI) is a common and life-threatening complication. Current treatment options are limited, and mortality remains very high.

Vitamin C is a low-cost, widely available antioxidant and immune-modulating agent. It has shown promising results in patients with sepsis and septic shock by reducing oxidative stress, improving vascular tone, and supporting immune defense. However, its role in ACLF patients with septic shock and AKI has not been studied in a large, controlled trial.

This interventional, randomized, open-label controlled trial will enroll patients with alcohol-related ACLF, septic shock, and AKI. Participants will be randomized 1:1 to receive either intravenous Vitamin C in addition to standard medical care, or standard care alone. Clinical outcomes, including resolution of shock, progression or resolution of AKI, need for renal replacement therapy, ICU/hospital stay, and survival at 7 and 28 days will be assessed. In addition, biospecimens (blood and urine) will be analyzed to identify biomarkers that predict outcomes and response to Vitamin C therapy.

The study aims to provide evidence on the effectiveness of Vitamin C as an adjunctive therapy in this high-risk population, and to generate insights into the mechanisms of septic shock and kidney injury in ACLF.

Interventions

• Drug Vitamin C
  Intravenous Vitamin C, 25 mg/kg (maximum 1.5 g) every 6 hours for 5 days, administered in addition to standard medical treatment
• Other Standard of Care (SOC)
  Supportive and guideline-based management of ACLF with septic shock and AKI, including antibiotics, fluids, vasopressors, renal replacement therapy as required, and other standard therapies

Primary outcome measures

• Resolution of septic shock at 96 hours (Day 4) [Time frame: Day 4 (96 hours) after randomization]

Secondary outcome measures (7)

• Outcome of acute kidney injury (AKI) at Day 7 [Time frame: Day 7]
• Incidence of adverse events [Time frame: Day 7, Day 14, Day 28 or until hospital discharge, whichever occurs first]
• Need for renal replacement therapy [Time frame: Day 7]
• Duration of ICU stay [Time frame: Through hospital discharge or death, up to 28 days]
• Duration of hospital stay [Time frame: Up to Day 28]
• 7-day mortality [Time frame: Day 7]
• 28-day mortality [Time frame: Day 28]

Eligibility criteria

Inclusion criteria

• ACLF as per asia pacific association for the study of liver (APASL criteria) with AKI according to KDIGO Criteria and septic shock.

Exclusion criteria

• • Refractory Septic shock with more than 3 organ failures.

• 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,
• 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 stones
• History of chronic kidney disease or intrinsic kidney disease
• Patients already on maintenance hemodialysis prior to presentation
• Failure to provide informed consent
• Patients with retroviral infection
• Patients with active hemolysis due to alcohol or other causes or with hemoglobin below 7 gm/dl

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07184866 · IEC/2024/116/MA02 · IEC approval number

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗