Parenteral Ascorbic Acid Repletion in TransplantatIon (PARTI)

University of Wisconsin (UW)

Status and phase: Suspended; Phase 4

Conditions: Liver Transplant Failure and Rejection

Treatments: Other: Placebo; Drug: Ascorbic acid

Study type: Interventional

Funder types: Other

Identifiers

NCT04756063

Protocol Version 12/5/2024 (Other Identifier)

SMPH/ANESTHESIOLOGY (Other Identifier)

2020-1153

A530900 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 90 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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90 participants in 2 patient groups, including a placebo group

Ascorbic Acid (AA)

Experimental group

Description:

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

Treatment:

Drug: Ascorbic acid

Placebo

Placebo Comparator group

Description:

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

Treatment:

Other: Placebo