Liver Transplant Failure and Rejection
Conditions
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.
Interventions
DRUGAscorbic acid
Intravenous vitamin C
OTHERPlacebo
Normal Saline
Sponsors
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Serum AA Levels | Pre-treatment (baseline) and Post-treatment (up to 1 week) | — |
| Total Vasopressor Dose in Norepinephrine Equivalents per Kilogram | from start of anesthesia (day 1) to end of ICU stay (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. |
| Days on Ventilator | postoperative (up to ~ 7 days) | — |
| Incidence of Infection | postoperative (up to ~ 7 days) | Surgical site, bloodstream \& intra-abdominal infection rates |
| Length of ICU stay | postoperative (up to ~ 7 days) | — |
| Length of Hospital stay | postoperative (up to ~ 30 days) | — |
| 30 day Mortality | up to 30 days post-op | — |
| 1-year Mortality | up to 1-year post-op | — |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMolly Groose, MD, MS
University of Wisconsin, Madison
Outcome results
None listed