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Primary Graft DysfunctionPhase 2NCT04505878

Perioperative Vitamin C Lung Transplant

A Phase 2 study testing Vitamin C in people with Primary Graft Dysfunction and Lung Transplant; Complications, run by University of Wisconsin, Madison.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 yearsHealthy volunteers can take part
What is being tested?
Vitamin C
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Apr 2023to Dec 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Participant is scheduled for lung transplantation

Who cannot join

  • 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.)
Show all 14Show fewer
  • 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.

About this study

Official title: Vitamin C: Assessing Safety After Lung Transplant

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.

Read the 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
Being tested
Vitamin C
Keywords
Vitamin C
Medical subject headings
Primary Graft Dysfunction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Vitamin CDrug

    Also called ascorbic acid

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

Study groups in NCT04505878
Study groupRoleWhat they receive
Vitamin C ArmExperimentalAscorbic 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
Receives: Drug: Vitamin C

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: Post Operative Day 1

  2. 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).

    Measured: Post Operative Day 2

  3. 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).

    Measured: Post Operative Day 3

  4. 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).

    Measured: Post Operative Day 4

  5. 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).

    Measured: Post Operative Day 7

  6. Incidence of New Dialysis Initiation

    Measured: up to Post Operative Day 7

Secondary outcomes (22)
  1. Participant Vitamin C Levels

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

  2. Participant Thiamine Levels

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

  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.

    Measured: up to Post Operative Day 7

  4. 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.

    Measured: Post Operative Day 3

  5. Tacrolimus Levels

    Measured: Post Operative Days 2, 3, 4, and 7

  6. Tacrolimus Doses

    Measured: Post Operative Days 4 and 7

  7. Post-Operative Well Being: Mortality

    Measured: at Post Operative Day 30 and Post Operative Day 90 via chart review

  8. Post-Operative Well Being: Atrial Fibrillation

    Measured: up to Post Operative Day 7

  9. Post-Operative Well Being: ICU Length of Stay

    Measured: up to Post Operative Day 30 (chart review)

  10. Post-Operative Well Being: Hospital Length of Stay

    Measured: up to Post Operative Day 90 (chart review)

  11. Post-Operative Well Being: Nadir Cardiac Index

    Measured: up to 72 hours post op

  12. Post-Operative Well Being: Peak Pulmonary Artery Systolic Pressure

    Measured: up to 72 hours post op

  13. Post-Operative Well Being: Peak Pulmonary Artery Diastolic Pressure

    Measured: up to 72 hours post op

  14. Post-Operative Well Being: Duration of Inotrope Need

    Measured: up to 72 hours post op

  15. Post-Operative Well Being: Duration of Vasopressor

    Measured: up to 72 hours post op

  16. Post-Operative Well Being: Total Dose of Vasopressor

    Measured: up to 72 hours post op

  17. Post-Operative Well Being: Daily Crystalloid Volume

    for 0-24h, 24-48h and 48-72h; total volume balance at 72-hours

    Measured: up to 72 hours post op

  18. Post-Operative Well Being: Daily Blood Product Transfusion Volume

    for 0-24h, 24-48h and 48-72h; total volume balance at 72-hours

    Measured: up to 72 hours post op

  19. Post-Operative Well Being: Daily Chest Tube Output Volume

    for 0-24h, 24-48h and 48-72h; total volume balance at 72-hours

    Measured: up to 72 hours post op

  20. Post-Operative Well Being: Duration of Post-Operative Mechanical Ventilation

    Measured: up to Post Operative Day 7

  21. 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 %).

    Measured: Post Operative Day 1, Post Operative Day 2, Post Operative Day 3

  22. Post-Operative Well Being: Time to Clearance of Lactate

    "Clearance" is defined as a lactate <1 mmol/L.

    Measured: up to Post Operative Day 3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Aug 2020
  2. Study startApr 2023 (estimated)
  3. Primary completionDec 2023 (estimated)
  4. Study completionDec 2023 (estimated)

Why it stopped: Decided not to proceed with study

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
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)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04505878
Sponsor's protocol ID
2020-0503
Other IDs
A530900, SMPH/ANESTHESIOLOGY, Protocol Version 0.05
Status last verified
Apr 2023
First submitted
5 Aug 2020
Last updated
1 May 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
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.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Vitamin C in people with Primary Graft Dysfunction and Lung Transplant; Complications, run by University of Wisconsin, Madison.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 1 May 2023. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence and Severity of Kidney Injury Post Operative Day (POD) 1 (time frame: Post Operative Day 1). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2023.

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