Perioperative Vitamin C Lung Transplant

NCT ID: NCT04505878

Last Updated: 2023-05-01

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-30
• Study Completion Date: 2023-12-31

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.

Detailed Description

PGD is a frequent and severe outcome that impacts both short- and long-term outcomes after lung transplantation. Major pathophysiologic contributors include ischemia and reperfusion injury, mitochondrial dysfunction and endothelial failure. No directed therapy exists. Vitamin C is a first-line antioxidant that also acts at the endothelium and mitochondria to decrease permeability and leak, inhibit mitochondrial dysfunction and improve ischemia and reperfusion. When combined with steroids, part of standard care for lung transplant recipients, these effects may be enhanced and synergistically inhibit instigators of patient injury. A pilot trial will ensure safety of this potential intervention and guide future research into this important outcome measure. It will be readily received in the literature.

For the present study, vitamin C will be administered parenterally at a dose of 1,500 mg every 6 hours, a dose that is widely accepted and used in other clinical contexts where the drug is studied, such as sepsis. This will predictably reconstitute levels and achieve supratherapeutic benefit towards oxidant scavenging, while avoiding the potential pro-oxidant effects seen at exceedingly high doses. To this end, the investigators will exclude patients where the standard dosing of vitamin C will exceed 100 mg/kg/day (excluding patients <60 kg). Dosing will continue through post-operative day (POD) 3 to effectively assess for the impact of vitamin C on PGD.

Primary Objectives

• To assess whether parenterally administered ascorbic acid (vitamin C) is safe in the lung transplant population
• To estimate adherence to ascorbic acid administration protocol in this study population and to identify obstacles to feasibility of future trials using this protocol

Secondary Objectives

• To assess whether parenterally administered ascorbic acid (vitamin C) may decrease the rate and severity of PGD after lung transplant
• To establish the incidence of vitamin C and vitamin B1 (thiamine) deficiencies in the lung transplant population, and the responsiveness of vitamin C levels to our selected parenteral therapy
• To identify interventions that will optimize the post-operative wellbeing of patients receiving lung transplants by decreasing primary graft dysfunction (short and intermediate-to-long term

Stop Criteria

• Anuria x 3-hours
• Moderate, Grade 2 AKI (doubling of baseline creatinine)
• An acute, unexplained hemoglobin drop of >2 mg/dL

Conditions

Primary Graft Dysfunction; Lung Transplant; Complications

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vitamin C Arm

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

Group Type: EXPERIMENTAL

Vitamin C

Intervention Type: 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

Interventions

Vitamin C

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

Intervention Type: DRUG

Other Intervention Names

ascorbic acid

Eligibility Criteria

Inclusion Criteria

• Participant is scheduled for lung transplantation

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Wisconsin, Madison

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Micah Long, MD

Role: PRINCIPAL_INVESTIGATOR

UW School of Medicine and Public Health

Other Identifiers

A530900

Identifier Type: OTHER

Identifier Source: secondary_id

SMPH/ANESTHESIOLOGY

Identifier Type: OTHER

Identifier Source: secondary_id

Protocol Version 0.05

Identifier Type: OTHER

Identifier Source: secondary_id

2020-0503

Identifier Type: -

Identifier Source: org_study_id