Perioperative Vitamin C Lung Transplant

University of Wisconsin (UW)

Status and phase

Withdrawn

Phase 2

Conditions

Primary Graft Dysfunction

Lung Transplant; Complications

Treatments

Drug: Vitamin C

Study type

Interventional

Funder types

Other

Identifiers

NCT04505878

SMPH/ANESTHESIOLOGY (Other Identifier)

A530900 (Other Identifier)

2020-0503

Protocol Version 0.05 (Other Identifier)

Details and patient eligibility

About

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.

Full 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

Sex

All

Ages

18 to 80 years old

Volunteers

Accepts Healthy Volunteers

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.