Perioperative Vitamin C Lung Transplant
Primary Purpose
Primary Graft Dysfunction, Lung Transplant; Complications
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Vitamin C
Sponsored by

About this trial
This is an interventional treatment trial for Primary Graft Dysfunction focused on measuring Vitamin C
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.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Vitamin C Arm
Arm Description
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
Outcomes
Primary Outcome Measures
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).
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).
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).
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).
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).
Incidence of New Dialysis Initiation
Secondary Outcome Measures
Participant Vitamin C Levels
Participant Thiamine Levels
Incidence of Primary Graft Dysfunction (PGD)
Primary Graft Dysfunction is defined as chest x-ray (CXR)-infiltrates with or without depressed oxygenation function, assessed by the "PF-Ratio," which is the PaO2 / FiO2.
Incidence and Severity of PGD on POD 3
Primary Graft Dysfunction is defined as chest x-ray (CXR)-infiltrates with or without depressed oxygenation function, assessed by the "PF-Ratio," which is the PaO2 / FiO2. Severity is defined as: PGD Grade 1 = CXR findings and any PF Ratio > 300; PGD Grade 2 = CXR findings and PF Ratio 200-300; and PGD Grade 3 = CXR findings and PF Ratio <200.
Tacrolimus Levels
Tacrolimus Doses
Post-Operative Well Being: Mortality
Post-Operative Well Being: Atrial Fibrillation
Post-Operative Well Being: ICU Length of Stay
Post-Operative Well Being: Hospital Length of Stay
Post-Operative Well Being: Nadir Cardiac Index
Post-Operative Well Being: Peak Pulmonary Artery Systolic Pressure
Post-Operative Well Being: Peak Pulmonary Artery Diastolic Pressure
Post-Operative Well Being: Duration of Inotrope Need
Post-Operative Well Being: Duration of Vasopressor
Post-Operative Well Being: Total Dose of Vasopressor
Post-Operative Well Being: Daily Crystalloid Volume
for 0-24h, 24-48h and 48-72h; total volume balance at 72-hours
Post-Operative Well Being: Daily Blood Product Transfusion Volume
for 0-24h, 24-48h and 48-72h; total volume balance at 72-hours
Post-Operative Well Being: Daily Chest Tube Output Volume
for 0-24h, 24-48h and 48-72h; total volume balance at 72-hours
Post-Operative Well Being: Duration of Post-Operative Mechanical Ventilation
Post-Operative Well Being: PaO2 / FIO2 ratios
The PF Ratio assesses the lungs' ability to oxygenate the blood. It is defined as the ratio of the partial pressure of oxygen in the arteries (PaO2 in mmHg) to the fractional inspired oxygen content from the ventilator (FiO2 in %).
Post-Operative Well Being: Time to Clearance of Lactate
"Clearance" is defined as a lactate <1 mmol/L.
Full Information
NCT ID
NCT04505878
First Posted
August 5, 2020
Last Updated
April 27, 2023
Sponsor
University of Wisconsin, Madison
1. Study Identification
Unique Protocol Identification Number
NCT04505878
Brief Title
Perioperative Vitamin C Lung Transplant
Official Title
Vitamin C: Assessing Safety After Lung Transplant
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Withdrawn
Why Stopped
Decided not to proceed with study
Study Start Date
April 2023 (Anticipated)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Wisconsin, Madison
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Graft Dysfunction, Lung Transplant; Complications
Keywords
Vitamin C
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Vitamin C Arm
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Vitamin C
Other Intervention Name(s)
ascorbic acid
Intervention Description
Vitamin C is a first-line antioxidant that directly scavenges free radicals, inhibits reactive oxygen species (ROS) producing enzymes and recovers other cellular antioxidants
Primary Outcome Measure Information:
Title
Incidence and Severity of Kidney Injury Post Operative Day (POD) 1
Description
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).
Time Frame
Post Operative Day 1
Title
Incidence and Severity of Kidney Injury POD 2
Description
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).
Time Frame
Post Operative Day 2
Title
Incidence and Severity of Kidney Injury POD 3
Description
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).
Time Frame
Post Operative Day 3
Title
Incidence and Severity of Kidney Injury POD 4
Description
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).
Time Frame
Post Operative Day 4
Title
Incidence and Severity of Kidney Injury POD 7
Description
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).
Time Frame
Post Operative Day 7
Title
Incidence of New Dialysis Initiation
Time Frame
up to Post Operative Day 7
Secondary Outcome Measure Information:
Title
Participant Vitamin C Levels
Time Frame
Baseline, Post Operative Day 1, Post Operative Day 2, Post Operative Day 3
Title
Participant Thiamine Levels
Time Frame
Baseline, Post Operative Day 1, Post Operative Day 2, Post Operative Day 3
Title
Incidence of Primary Graft Dysfunction (PGD)
Description
Primary Graft Dysfunction is defined as chest x-ray (CXR)-infiltrates with or without depressed oxygenation function, assessed by the "PF-Ratio," which is the PaO2 / FiO2.
Time Frame
up to Post Operative Day 7
Title
Incidence and Severity of PGD on POD 3
Description
Primary Graft Dysfunction is defined as chest x-ray (CXR)-infiltrates with or without depressed oxygenation function, assessed by the "PF-Ratio," which is the PaO2 / FiO2. Severity is defined as: PGD Grade 1 = CXR findings and any PF Ratio > 300; PGD Grade 2 = CXR findings and PF Ratio 200-300; and PGD Grade 3 = CXR findings and PF Ratio <200.
Time Frame
Post Operative Day 3
Title
Tacrolimus Levels
Time Frame
Post Operative Days 2, 3, 4, and 7
Title
Tacrolimus Doses
Time Frame
Post Operative Days 4 and 7
Title
Post-Operative Well Being: Mortality
Time Frame
at Post Operative Day 30 and Post Operative Day 90 via chart review
Title
Post-Operative Well Being: Atrial Fibrillation
Time Frame
up to Post Operative Day 7
Title
Post-Operative Well Being: ICU Length of Stay
Time Frame
up to Post Operative Day 30 (chart review)
Title
Post-Operative Well Being: Hospital Length of Stay
Time Frame
up to Post Operative Day 90 (chart review)
Title
Post-Operative Well Being: Nadir Cardiac Index
Time Frame
up to 72 hours post op
Title
Post-Operative Well Being: Peak Pulmonary Artery Systolic Pressure
Time Frame
up to 72 hours post op
Title
Post-Operative Well Being: Peak Pulmonary Artery Diastolic Pressure
Time Frame
up to 72 hours post op
Title
Post-Operative Well Being: Duration of Inotrope Need
Time Frame
up to 72 hours post op
Title
Post-Operative Well Being: Duration of Vasopressor
Time Frame
up to 72 hours post op
Title
Post-Operative Well Being: Total Dose of Vasopressor
Time Frame
up to 72 hours post op
Title
Post-Operative Well Being: Daily Crystalloid Volume
Description
for 0-24h, 24-48h and 48-72h; total volume balance at 72-hours
Time Frame
up to 72 hours post op
Title
Post-Operative Well Being: Daily Blood Product Transfusion Volume
Description
for 0-24h, 24-48h and 48-72h; total volume balance at 72-hours
Time Frame
up to 72 hours post op
Title
Post-Operative Well Being: Daily Chest Tube Output Volume
Description
for 0-24h, 24-48h and 48-72h; total volume balance at 72-hours
Time Frame
up to 72 hours post op
Title
Post-Operative Well Being: Duration of Post-Operative Mechanical Ventilation
Time Frame
up to Post Operative Day 7
Title
Post-Operative Well Being: PaO2 / FIO2 ratios
Description
The PF Ratio assesses the lungs' ability to oxygenate the blood. It is defined as the ratio of the partial pressure of oxygen in the arteries (PaO2 in mmHg) to the fractional inspired oxygen content from the ventilator (FiO2 in %).
Time Frame
Post Operative Day 1, Post Operative Day 2, Post Operative Day 3
Title
Post-Operative Well Being: Time to Clearance of Lactate
Description
"Clearance" is defined as a lactate <1 mmol/L.
Time Frame
up to Post Operative Day 3
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Micah Long, MD
Organizational Affiliation
UW School of Medicine and Public Health
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Data from this study may be requested from other researchers up to 7 years after the completion of the primary endpoint by contacting Dr. Micah Long, the Principal Investigator of this study.
IPD Sharing Time Frame
up to 7 years after the completion of the primary endpoint
Learn more about this trial
Perioperative Vitamin C Lung Transplant
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