A Phase 2 interventional study of Vitamin C in Primary Graft Dysfunction and Lung Transplant; Complications, sponsored by University of Wisconsin, Madison. Withdrawn. Open to participants aged 18 Years to 80 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-05-01.
Sponsored by University of Wisconsin, Madison · Phase 2, Interventional, and Treatment
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.
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
Secondary Objectives
Stop Criteria
26 studies on the registry are indexed under Primary Graft Dysfunction; 4 are open to participants now.
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Exclusion Criteria:
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
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
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).
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: Post Operative Day 7
Incidence of New Dialysis Initiation
Time frame: up to Post Operative Day 7
Participant Vitamin C Levels
Time frame: Baseline, Post Operative Day 1, Post Operative Day 2, Post Operative Day 3
Participant Thiamine Levels
Time frame: Baseline, Post Operative Day 1, Post Operative Day 2, Post Operative Day 3
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.
Time frame: up to Post Operative Day 7
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.
Time frame: Post Operative Day 3
Tacrolimus Levels
Time frame: Post Operative Days 2, 3, 4, and 7
Tacrolimus Doses
Time frame: Post Operative Days 4 and 7
Post-Operative Well Being: Mortality
Time frame: at Post Operative Day 30 and Post Operative Day 90 via chart review
Post-Operative Well Being: Atrial Fibrillation
Time frame: up to Post Operative Day 7
Post-Operative Well Being: ICU Length of Stay
Time frame: up to Post Operative Day 30 (chart review)
Post-Operative Well Being: Hospital Length of Stay
Time frame: up to Post Operative Day 90 (chart review)
Post-Operative Well Being: Nadir Cardiac Index
Time frame: up to 72 hours post op
Post-Operative Well Being: Peak Pulmonary Artery Systolic Pressure
Time frame: up to 72 hours post op
Post-Operative Well Being: Peak Pulmonary Artery Diastolic Pressure
Time frame: up to 72 hours post op
Post-Operative Well Being: Duration of Inotrope Need
Time frame: up to 72 hours post op
Post-Operative Well Being: Duration of Vasopressor
Time frame: up to 72 hours post op
Post-Operative Well Being: Total Dose of Vasopressor
Time frame: up to 72 hours post op
Post-Operative Well Being: Daily Crystalloid Volume
for 0-24h, 24-48h and 48-72h; total volume balance at 72-hours
Time frame: up to 72 hours post op
Post-Operative Well Being: Daily Blood Product Transfusion Volume
for 0-24h, 24-48h and 48-72h; total volume balance at 72-hours
Time frame: up to 72 hours post op
Post-Operative Well Being: Daily Chest Tube Output Volume
for 0-24h, 24-48h and 48-72h; total volume balance at 72-hours
Time frame: up to 72 hours post op
Post-Operative Well Being: Duration of Post-Operative Mechanical Ventilation
Time frame: up to Post Operative Day 7
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 %).
Time frame: Post Operative Day 1, Post Operative Day 2, Post Operative Day 3
Post-Operative Well Being: Time to Clearance of Lactate
"Clearance" is defined as a lactate \<1 mmol/L.
Time frame: up to Post Operative Day 3
No study locations are listed for this record.
Plan to share: Yes — 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.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report
Time frame: up to 7 years after the completion of the primary endpoint
No publications or documents are linked to this record.
This study is withdrawn, as verified in Apr 2023. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Ascorbic Acid
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