Vitamin C: Assessing Safety After Lung Transplant
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Incidence and Severity of Kidney Injury POD 4
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participant is scheduled for lung transplantation
排除标准
- •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.
研究组 & 干预措施
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
干预措施: Vitamin C (Drug)
结局指标
主要结局
Incidence and Severity of Kidney Injury POD 4
时间窗: Post Operative Day 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
时间窗: Post Operative Day 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
时间窗: up to Post Operative Day 7
Incidence and Severity of Kidney Injury Post Operative Day (POD) 1
时间窗: Post Operative Day 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
时间窗: Post Operative Day 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
时间窗: Post Operative Day 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).
次要结局
- Participant Vitamin C Levels(Baseline, Post Operative Day 1, Post Operative Day 2, Post Operative Day 3)
- Participant Thiamine Levels(Baseline, Post Operative Day 1, Post Operative Day 2, Post Operative Day 3)
- Incidence of Primary Graft Dysfunction (PGD)(up to Post Operative Day 7)
- Incidence and Severity of PGD on POD 3(Post Operative Day 3)
- Tacrolimus Levels(Post Operative Days 2, 3, 4, and 7)
- Tacrolimus Doses(Post Operative Days 4 and 7)
- Post-Operative Well Being: Mortality(at Post Operative Day 30 and Post Operative Day 90 via chart review)
- Post-Operative Well Being: Atrial Fibrillation(up to Post Operative Day 7)
- Post-Operative Well Being: ICU Length of Stay(up to Post Operative Day 30 (chart review))
- Post-Operative Well Being: Hospital Length of Stay(up to Post Operative Day 90 (chart review))
- Post-Operative Well Being: Nadir Cardiac Index(up to 72 hours post op)
- Post-Operative Well Being: Peak Pulmonary Artery Systolic Pressure(up to 72 hours post op)
- Post-Operative Well Being: Peak Pulmonary Artery Diastolic Pressure(up to 72 hours post op)
- Post-Operative Well Being: Duration of Inotrope Need(up to 72 hours post op)
- Post-Operative Well Being: Duration of Vasopressor(up to 72 hours post op)
- Post-Operative Well Being: Total Dose of Vasopressor(up to 72 hours post op)
- Post-Operative Well Being: Daily Crystalloid Volume(up to 72 hours post op)
- Post-Operative Well Being: Daily Blood Product Transfusion Volume(up to 72 hours post op)
- Post-Operative Well Being: Daily Chest Tube Output Volume(up to 72 hours post op)
- Post-Operative Well Being: Duration of Post-Operative Mechanical Ventilation(up to Post Operative Day 7)
- Post-Operative Well Being: PaO2 / FIO2 ratios(Post Operative Day 1, Post Operative Day 2, Post Operative Day 3)
- Post-Operative Well Being: Time to Clearance of Lactate(up to Post Operative Day 3)