Parenteral Ascorbic Acid Repletion in TransplantatIon (PARTI): A Randomized, Double-Blinded, Placebo-Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 暂停
- 入组人数
- 90
- 试验地点
- 2
- 主要终点
- Change in Sequential Organ Failure Assessment (SOFA) Score
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subject is scheduled to undergo primary deceased donor solidary liver transplantation
排除标准
- •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
研究组 & 干预措施
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
干预措施: Placebo (Other)
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
干预措施: Ascorbic acid (Drug)
结局指标
主要结局
Change in Sequential Organ Failure Assessment (SOFA) Score
时间窗: 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.
次要结局
- 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))
- Postoperative Day 7 SOFA Score(postoperative (up to 3 days))
- 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))
- 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)