Parenteral Ascorbic Acid Repletion in TransplantatIon

Phase 4

Recruiting

• Conditions: Liver Transplant Failure and Rejection
• Interventions: Drug: Ascorbic acid; Other: Placebo

• Registration Number: NCT04756063
• Lead Sponsor: University of Wisconsin, Madison

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2021-02-11
• Study First Submitted QC: 2021-02-15
• Study First Posted: 2021-02-16
• Status Verified: 2024-11
• Last Update Submitted: 2025-04-21
• Last Update Posted: 2025-04-22
• Study Start: 2025-05
• Primary Completion: 2030-01
• Study Completion: 2031-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

• The subject is scheduled to undergo primary deceased donor solidary liver transplantation

Exclusion Criteria

• Non-English speaking
• Known or believed to be pregnant
• Subject is a prisoner
• Impaired decision-making capacity (i.e., current encephalopathy)
• Known allergy to AA
• Concurrent organ transplantation (i.e., simultaneous liver-kidney transplantation)
• Planned veno-venous bypass use in the operating room
• Prior parenteral or oral AA repletion
• History of nephrolithiasis or oxaluria
• Vitamin C supplement use or administration (including HAT therapy) within the last month prior to transplantation
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Sickle cell anemia
• Hereditary hemochromatosis
• Preoperative anuria or creatinine >2.5mg/dL in patient not on renal replacement therapy
• Current enrollment in another research study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ascorbic Acid (AA)	Ascorbic acid	The first intravenous dosage of 1500mg of AA in 100mL of normal saline (NS) will be administered after induction of general anesthesia and invasive line placement prior to surgical incision. An identical dosage will be delivered approximately every 6 hours for the first 48 hours, for a total of 8 doses
Placebo	Placebo	The first intravenous dosage of placebo (100 mL of NS) will be administered after induction of general anesthesia and invasive line placement prior to surgical incision. An identical dosage will be delivered approximately every 6 hours for the first 48 hours, for a total of 8 doses

Primary Outcome Measures

Name	Time	Method
Change in Sequential Organ Failure Assessment (SOFA) Score	baseline to 3 days after first dose	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.

Secondary Outcome Measures

Name	Time	Method
Serum AA Levels	Pre-treatment (baseline) and Post-treatment (up to 1 week)
Incidence of Early Graft Dysfunction	postoperative (up to 7 days or until discharge, whichever came first)	As defined per Olthoff as: total bilirubin ≥10 or INR≥1.6 on day 7, or transaminase \>2000 within first 7 days
Postoperative Day 7 SOFA Score	postoperative (up to 3 days)	Total range of scores 0-24 where higher scores indicate higher dysfunction.
Total Vasopressor Dose in Norepinephrine Equivalents per Kilogram	from start of anesthesia (day 1) to end of ICU stay (up to 1 week)
Days on Ventilator	postoperative (up to ~ 7 days)
Length of Hospital stay	postoperative (up to ~ 30 days)
Incidence of Infection	postoperative (up to ~ 7 days)	Surgical site, bloodstream \& intra-abdominal infection rates
30 day Mortality	up to 30 days post-op
Length of ICU stay	postoperative (up to ~ 7 days)
1-year Mortality	up to 1-year post-op

Trial Locations

Locations (1)

University of Wisconsin Hospital and Clinics; 🇺🇸 Madison, Wisconsin, United States