Perioperative Vitamin C Lung Transplant

NCT04505878 | Withdrawn Phase 2 DMC FDA Drug

• 4 other identifiers: 2020-0503A530900SMPH/ANESTHESIOLOGYProtocol Version 0.05
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is being done to determine if parenterally administered ascorbic acid (Vitamin C) given at the time of lung transplant is safe. Vitamin C may be an effective intervention towards primary graft dysfunction (PGD). The study will enroll 69 participants who consent to the intervention. Participants who do not consent to the intervention will be treated according to standard-of-care, but may choose to be consented to have their data retrospectively reviewed. Based on our consent rate, this group may include 40-70 participants. Participants will be on study for up to 12 months.

Conditions

Primary Graft Dysfunction; Lung Transplant; Complications

Keywords

Vitamin C

Outcome Measures

Primary Outcomes (6)

• Incidence and Severity of Kidney Injury Post Operative Day (POD) 1

  The primary endpoint is the safety of the vitamin C intervention. This will be measured by the incidence and severity of kidney injuries on POD 1, POD 2, POD 3, POD 4, and POD 7. Acute kidney injury (AKI) is defined as any creatinine (Cr) that is 1.5-times the participant's baseline / immediate preoperative creatinine. Severity escalates with increasing ratios: Mild, stage 1 AKI (Cr 1.5-1.99x baseline); Moderate, stage 2 AKI (Cr 2-2.9x baseline); and Severe, stage 3 AKI (Cr \>3x baseline or any initiation of dialysis).

  Post Operative Day 1

• Incidence and Severity of Kidney Injury POD 2

  The primary endpoint is the safety of the vitamin C intervention. This will be measured by the incidence and severity of kidney injuries on POD 1, POD 2, POD 3, POD 4, and POD 7. Acute kidney injury (AKI) is defined as any creatinine (Cr) that is 1.5-times the participant's baseline / immediate preoperative creatinine. Severity escalates with increasing ratios: Mild, stage 1 AKI (Cr 1.5-1.99x baseline); Moderate, stage 2 AKI (Cr 2-2.9x baseline); and Severe, stage 3 AKI (Cr \>3x baseline or any initiation of dialysis).

  Post Operative Day 2

• Incidence and Severity of Kidney Injury POD 3

  The primary endpoint is the safety of the vitamin C intervention. This will be measured by the incidence and severity of kidney injuries on POD 1, POD 2, POD 3, POD 4, and POD 7. Acute kidney injury (AKI) is defined as any creatinine (Cr) that is 1.5-times the participant's baseline / immediate preoperative creatinine. Severity escalates with increasing ratios: Mild, stage 1 AKI (Cr 1.5-1.99x baseline); Moderate, stage 2 AKI (Cr 2-2.9x baseline); and Severe, stage 3 AKI (Cr \>3x baseline or any initiation of dialysis).

  Post Operative Day 3

• Incidence and Severity of Kidney Injury POD 4

  The primary endpoint is the safety of the vitamin C intervention. This will be measured by the incidence and severity of kidney injuries on POD 1, POD 2, POD 3, POD 4, and POD 7. Acute kidney injury (AKI) is defined as any creatinine (Cr) that is 1.5-times the participant's baseline / immediate preoperative creatinine. Severity escalates with increasing ratios: Mild, stage 1 AKI (Cr 1.5-1.99x baseline); Moderate, stage 2 AKI (Cr 2-2.9x baseline); and Severe, stage 3 AKI (Cr \>3x baseline or any initiation of dialysis).

  Post Operative Day 4

• Incidence and Severity of Kidney Injury POD 7

  The primary endpoint is the safety of the vitamin C intervention. This will be measured by the incidence and severity of kidney injuries on POD 1, POD 2, POD 3, POD 4, and POD 7. Acute kidney injury (AKI) is defined as any creatinine (Cr) that is 1.5-times the participant's baseline / immediate preoperative creatinine. Severity escalates with increasing ratios: Mild, stage 1 AKI (Cr 1.5-1.99x baseline); Moderate, stage 2 AKI (Cr 2-2.9x baseline); and Severe, stage 3 AKI (Cr \>3x baseline or any initiation of dialysis).

  Post Operative Day 7

• Incidence of New Dialysis Initiation

  up to Post Operative Day 7

Secondary Outcomes (22)

• Participant Vitamin C Levels

  Baseline, Post Operative Day 1, Post Operative Day 2, Post Operative Day 3

• Participant Thiamine Levels

  Baseline, Post Operative Day 1, Post Operative Day 2, Post Operative Day 3

• Incidence of Primary Graft Dysfunction (PGD)

  up to Post Operative Day 7

• Incidence and Severity of PGD on POD 3

  Post Operative Day 3

• Tacrolimus Levels

  Post Operative Days 2, 3, 4, and 7

Study Arms (1)

Vitamin C Arm

EXPERIMENTAL

Ascorbic Acid will be administered at a dose of 1500 mg in 100 mL of saline over 30 minutes intravenously once every 6 hours for a total of 72 hours

Drug: Vitamin C

Interventions

Vitamin C DRUG

Vitamin C is a first-line antioxidant that directly scavenges free radicals, inhibits reactive oxygen species (ROS) producing enzymes and recovers other cellular antioxidants

Also known as: ascorbic acid

Vitamin C Arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is scheduled for lung transplantation

You may not qualify if:

• Non-English speaking
• Subject is known or believed to be pregnant
• Subject is a prisoner.
• Subject has impaired decision-making capacity.
• Subject has known allergy to vitamin C.
• Subject has history of nephrolithiasis, oxalosis or hyperoxaluria. (Cystic Fibrosis patients are at risk of occult oxalosis / hyperoxaluria, therefore they will also be excluded from the study.)
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Sickle cell anemia
• Heredity hemochromatosis
• Baseline creatinine \>2 mg/dL or any current kidney injury
• Weight \<60 kg
• Vitamin C supplement use or administration (including HAT therapy) within the last month prior to transplantation
• Current enrolment in another research study
• Not suitable for study participation due to other reasons at the discretion of the investigators.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead

MeSH Terms

Conditions

Primary Graft Dysfunction

Interventions

Ascorbic Acid

Condition Hierarchy (Ancestors)

Reperfusion Injury; Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Study Officials

• Micah Long, MD

  UW School of Medicine and Public Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a pilot single-arm unblinded trial to assess whether parenterally administered ascorbic acid (vitamin C) is safe in the lung transplant population.The investigators will not randomize or control; a retrospective cohort of participants not treated with vitamin C will be reviewed from 2015-2020. Those participants who decline the intervention will have the choice to consent to having their data be considered as part of the (non-retrospective) controls and be considered in our statistical analysis for outcomes, including analysis between this group and the historical controls. All participants who consent will be administered the therapy and participants will be evaluated via an intention-to-treat analysis.

Study Record Dates

• First Submitted: August 5, 2020
• First Posted: August 10, 2020
• Study Start: April 1, 2023
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: May 1, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: up to 7 years after the completion of the primary endpoint