Administration of Intravenous Vitamin C in Novel Coronavirus Infection and Decreased Oxygenation (AVoCaDO): A Phase I/II Safety, Tolerability, and Efficacy Clinical Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Number of Participants With Serious Adverse Reactions
研究概览
简要总结
Previous research has shown that high dose intravenous vitamin C (HDIVC) may benefit patients with sepsis, acute lung injury (ALI), and the acute respiratory distress syndrome (ARDS). However, it is not known if early administration of HDIVC could prevent progression to ARDS.
We hypothesize that HDIVC is safe and tolerable in Coronavirus disease 2019 (COVID-19) subjects given early or late in the disease course and may reduce the risk of respiratory failure requiring mechanical ventilation and development of ARDS along with reductions in supplemental oxygen demand and inflammatory markers.
详细描述
The purpose of this study is to assess the safety, tolerability, potential efficacy of high dose intravenous vitamin C (HDIVC) therapy for patients with COVID-19 and decreased oxygenation. COVID-19 is a rapidly evolving pandemic with numerous prediction models suggesting potential shortages in ventilators, ICU beds, and high rates of hospital mortality. Case-series suggest sepsis and the acute respiratory distress syndrome (ARDS) are driving hospitalizations, morbidity (ICU beds, ventilator use, organ failures), and mortality. A therapy is urgently needed to be given early in the disease course in order to attenuate the infectious and inflammatory process, reduce risk of intubation, and reduce progression of organ failure and ARDS. By administering HDIVC at the first objective sign of worsening oxygenation, documented by change in peripheral capillary oxygen saturation (SpO2) to fraction of inspired oxygen (FIO2) ratio (S/F) or decreased SpO2 at baseline (mild hypoxia group), HDIVC may reduce the inflammatory process and development of respiratory failure requiring intubation. We will also enroll patients already in respiratory failure on ventilators (severe hypoxia group) and document safety and tolerability in both cohorts. By calculating ventilator and ICU-free days, we can potentially signal clinically relevant endpoints that could be used in larger trials needed to answer a crucial therapeutic question-can early administration of HDIVC in COVID-19 lead to faster recovery or improve outcomes? Moreover, we will document change in inflammatory markers that are elevated in COVID-19 (d-dimer, C reactive protein (CRP), lactate dehydrogenase (LDH), liver enzymes, and ferritin) to develop a mechanistic understanding and risk stratification of response to HDIVC infusion. Ultimately, if HDIVC is deemed safe and tolerable in hospitalized COVID-19 subjects, a larger clinical trial will be indicated. AVoCaDO will produce safety and tolerability data to test HDIVC in a multi-center, rapid, randomized, placebo-controlled trial of subjects with COVID-19.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Hospitalized with diagnosis of COVID-19 based on positive reverse transcriptase polymerase chain reaction (RT-PCR) SARS-CoV-2 of nasal, oropharyngeal, or bronchoalveolar (BAL) specimen
- •Mild deoxygenation defined as S/F ratio decreased by 25% from baseline on admission, or SpO2 <95% breathing ambient air on admission
- •Non-childbearing potential or childbearing potential with a negative pregnancy test at screening, and using a reliable method of contraception (i.e., abstinence, hormonal contraception, intrauterine device (IUD), or vasectomized partner)
排除标准
- •Known allergy to Vitamin C
- •Inability to obtain consent from patient or next of kin
- •Chronic kidney disease, stage IV or above (eGFR <30)
- •Presence of diabetic ketoacidosis, use of insulin infusion, or frequent need for point-of-care glucose monitoring (>6 times/24 hour period) as determined by treating physician
- •History of glucose-6-phosphate dehydrogenase (G6PD) deficiency
- •Active or history of kidney stone within past 12 months
- •Pregnancy
- •Enrolled in another COVID-19 clinical trial that does not allow concomitant study drugs
研究组 & 干预措施
Mild hypoxemia
S/F ratio >250 prior to Vitamin C infusion
干预措施: L-ascorbic acid (Drug)
Severe Hypoxemia
S/F ratio ≤250 prior to Vitamin C infusion
干预措施: L-ascorbic acid (Drug)
结局指标
主要结局
Number of Participants With Serious Adverse Reactions
时间窗: Days 1-4
Number of participants with serious adverse events during study drug infusion
Number of Participants With Adverse Events Related to High Dose Intravenous Vitamin C (HDIVC)
时间窗: Days 1-4
Occurrence of adverse events during study drug infusion as defined in the Ascor package insert ie acute kidney injury (increase in serum creatinine 3x baseline prior to initial HDIVC dose, hemolysis, iatrogenic hypoglycemia, pain at swelling site of infusion, crystalluria on urinalysis (UA) after last HDIVC dose
Number of Participants With Adverse Reactions
时间窗: Days 1-4
Number of participants with adverse reactions during study drug infusion
次要结局
- All-cause Mortality(Days 1-28)
- Ventilator-free Days(Days 1-28)
- Change in S/F Ratio During High Dose Intravenous Vitamin C (HDIVC)(Days 1-4)
- Lymphocyte Count(Days 1-4)
- Intensive Care Unit (ICU)-Free Days(Days 1-28)
- C-reactive Protein (CRP)(Days 1-4)
- Serum Ferritin(Days 1-4)
- Hospital-free Days(Days 1-28)
- Lactate Dehydrogenase (LDH)(Days 1-4)
- D-dimer(Days 1-4)
- Neutrophil to Lymphocyte Ratio (NLR)(Days 1-4)
研究者
Brian C. Davis, MD
Staff Physician
Hunter Holmes Mcguire Veteran Affairs Medical Center