Parenteral Ascorbic Acid Repletion in TransplantatIon (PARTI)

• ClinicalTrials.gov Identifier: NCT04756063
• Recruitment Status: Not yet recruiting
• First Posted: February 16, 2021
• Last Update Posted: February 24, 2022
• Sponsor: University of Wisconsin, Madison
• Information provided by (Responsible Party): University of Wisconsin, Madison

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Liver Transplant Failure and Rejection	Drug: Ascorbic acid; Other: Placebo	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Parenteral Ascorbic Acid Repletion in TransplantatIon (PARTI): A Randomized, Double-Blinded, Placebo-Controlled Trial
• Estimated Study Start Date: April 2022
• Estimated Primary Completion Date: December 2025
• Estimated Study Completion Date: December 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ascorbic Acid (AA); 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	Drug: Ascorbic acid; Intravenous vitamin C; Other Names: vitamin C; ASCOR
Placebo Comparator: 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	Other: Placebo; Normal Saline

Outcome Measures

Primary Outcome Measures :

1. Change in Sequential Organ Failure Assessment (SOFA) Score [ Time Frame: 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 :

1. Serum AA Levels [ Time Frame: Pre-treatment (baseline) and Post-treatment (up to 1 week) ]
2. 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) ]
3. Incidence of Early Graft Dysfunction [ Time Frame: 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
4. Postoperative Day 7 SOFA Score [ Time Frame: postoperative (up to 3 days) ]
   Total range of scores 0-24 where higher scores indicate higher dysfunction.
5. Days on Ventilator [ Time Frame: postoperative (up to ~ 7 days) ]
6. Incidence of Infection [ Time Frame: postoperative (up to ~ 7 days) ]
   Surgical site, bloodstream & intra-abdominal infection rates
7. Length of ICU stay [ Time Frame: postoperative (up to ~ 7 days) ]
8. Length of Hospital stay [ Time Frame: postoperative (up to ~ 30 days) ]
9. 30 day Mortality [ Time Frame: up to 30 days post-op ]
10. 1-year Mortality [ Time Frame: up to 1-year post-op ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Helen Akere; (608) 265-3243; akere@wisc.edu

Locations

United States, Wisconsin

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States, 53792

Contact: Brian Payne 608-890-0156 bepayne@wisc.edu

Principal Investigator: Molly Groose, MD, MS

Sponsors and Collaborators

University of Wisconsin, Madison

Investigators

• Principal Investigator: Molly Groose, MD, MS; University of Wisconsin, Madison

More Information

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT04756063
• Other Study ID Numbers: 2020-1153; A530900 ( Other Identifier: UW Madison ); SMPH/ANESTHESIOLOGY ( Other Identifier: UW Madison ); Protocol Version 10/20/2020 ( Other Identifier: UW Madison )
• First Posted: February 16, 2021
• Last Update Posted: February 24, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Data from this study may be requested from other researchers up to 7 years after the completion of the primary endpoint by contacting Dr. Molly Groose, the Principal Investigator of this study
• Supporting Materials: Study Protocol
• Time Frame: up to 7 years after primary completion

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Ascorbic Acid; Vitamins; Micronutrients; Physiological Effects of Drugs; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents