A single-center, randomized, double-blinded placebo-controlled trial is proposed to investigate administration of supraphysiologic doses of ascorbic acid (vitamin C, AA) to patients undergoing liver transplantation. Participants randomized to the intervention group will receive intravenous (IV) AA 1500 mg every 6 hours for 48 hours. Participants randomized to the control group will receive a saline placebo. The primary study outcome will be a change in the Sequential Organ Failure Assessment (SOFA) score from baseline to three days after the first dose of drug (dSOFA3). Secondary outcomes will include total vasopressor dose in norepinephrine equivalents, 30-day and 1-year mortality, and serum AA levels.
HYPOTHESIS: Administration of supraphysiologic doses of parenteral AA in the perioperative period for patients undergoing liver transplantation will improve Sequential Organ Failure Assessment (SOFA) scores, vasopressor usage and biochemical, cellular and clinical end-organ damage. Specific Aim: Determine the clinical response to parenteral AA supplementation in patients undergoing liver transplantation by a randomized, double-blinded, placebo-controlled clinical trial. Study Design: This study is a prospective, single-center, randomized trial in which 90 participants will be enrolled at the University of Wisconsin Hospitals and Clinics (UWHC). Participants must meet study eligibility criteria and be scheduled to undergo primary deceased donor solitary liver transplantation. Participants will be randomized to receive 8 doses of 1500 mg AA IV or volume-equivalent placebo every 6 hours for 48 hours, in addition to standard medical management.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
90
Intravenous vitamin C
Normal Saline
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States
Change in Sequential Organ Failure Assessment (SOFA) Score
SOFA scores are a widely used composite measure of multiorgan dysfunction, validated as an accurate predictor of short- and long-term mortality in the general ICU and liver transplant populations. Change in SOFA from baseline (delta SOFA or dSOFA) has been shown to be more predictive of mortality than other derivatives such as absolute interval SOFA scores and has been recommended as the preferred endpoint in critical care settings The total possible range of scores is 0-24, higher scores are indicative of a higher degree of dysfunction.
Time frame: baseline to 3 days after first dose
Serum AA Levels
Time frame: Pre-treatment (baseline) and Post-treatment (up to 1 week)
Total Vasopressor Dose in Norepinephrine Equivalents per Kilogram
Time frame: from start of anesthesia (day 1) to end of ICU stay (up to 1 week)
Incidence of Early Graft Dysfunction
As defined per Olthoff as: total bilirubin ≥10 or INR≥1.6 on day 7, or transaminase \>2000 within first 7 days
Time frame: postoperative (up to 7 days or until discharge, whichever came first)
Postoperative Day 7 SOFA Score
Total range of scores 0-24 where higher scores indicate higher dysfunction.
Time frame: postoperative (up to 3 days)
Days on Ventilator
Time frame: postoperative (up to ~ 7 days)
Incidence of Infection
Surgical site, bloodstream \& intra-abdominal infection rates
Time frame: postoperative (up to ~ 7 days)
Length of ICU stay
Time frame: postoperative (up to ~ 7 days)
Length of Hospital stay
Time frame: postoperative (up to ~ 30 days)
30 day Mortality
Time frame: up to 30 days post-op
1-year Mortality
Time frame: up to 1-year post-op
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.