Clinical trial NCT04756063: Parenteral Ascorbic Acid Repletion in TransplantatIon
Official title: Parenteral Ascorbic Acid Repletion in TransplantatIon (PARTI): A Randomized, Double-Blinded, Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Liver Transplant Failure and Rejection
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
First posted: 2021-02-16
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Sequential Organ Failure Assessment (SOFA) Score
timeFrame: baseline to 3 days after first dose
Secondary outcomes:
measure: Serum AA Levels
timeFrame: Pre-treatment (baseline) and Post-treatment (up to 1 week)
measure: Total Vasopressor Dose in Norepinephrine Equivalents per Kilogram
timeFrame: from start of anesthesia (day 1) to end of ICU stay (up to 1 week)
measure: Incidence of Early Graft Dysfunction
timeFrame: postoperative (up to 7 days or until discharge, whichever came first)
measure: Postoperative Day 7 SOFA Score
timeFrame: postoperative (up to 3 days)
measure: Days on Ventilator
timeFrame: postoperative (up to ~ 7 days)
measure: Incidence of Infection
timeFrame: postoperative (up to ~ 7 days)
measure: Length of ICU stay
timeFrame: postoperative (up to ~ 7 days)
measure: Length of Hospital stay
timeFrame: postoperative (up to ~ 30 days)
measure: 30 day Mortality
timeFrame: up to 30 days post-op
measure: 1-year Mortality
timeFrame: up to 1-year post-op
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Molly Groose, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: