Lessening Organ Dysfunction With VITamin C (LOVIT)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 872
- 试验地点
- 1
- 主要终点
- Number of deceased participants or with persistent organ dysfunction
研究概览
简要总结
LOVIT is a multicentre concealed-allocation parallel-group blinded randomized controlled trial to ascertain the effect of high-dose intravenous vitamin C compared to placebo on mortality or persistent organ dysfunction at 28 days in septic intensive care unit patients. Patients with COVID-19 are considered eligible for this study.
详细描述
Background. The burden of sepsis is increasing worldwide. It is the cause of 8 million global deaths each year. Currently, treatment options are limited to antimicrobials and supportive care such as intravenous fluids, vasopressors, mechanical ventilation, and renal replacement therapy. In the absence of effective therapies specifically targeting the dysregulated immune response, prolonged use of these life-sustaining therapies can be debilitating. A growing body of evidence suggesting that vitamin C, an inexpensive and readily available intervention, is potentially lifesaving in sepsis. Intravenous vitamin C may be the first therapy to mitigate the dysregulated cascade of events that leads to sepsis. If proven effective, vitamin C could be used worldwide and drastically change outcomes in high- and low-income settings alike.
Objectives. To determine whether intravenous vitamin C, compared to placebo, reduces mortality and morbidity in sepsis (induced by bacterial and viral pathogens (as COVID-19)), and compare clinical and biochemical measures of organ dysfunction, and health-related quality of life (HRQoL) at 6 months. To ascertain the volume of distribution, clearance, and plasma concentration over a course of 96 hours of intravenous vitamin C 50 mg/kg of weight every 6 hours or matching placebo (pharmacokinetic (PK) substudy).
Methods. Patients will be randomly assigned to vitamin C (intravenous, 50 mg/kg every 6h) or placebo (0.9% NaCl or dextrose 5% in water) for 96 hours. Study personnel at the clinical sites will document the composite of death or persistent organ dysfunction at day 28. Daily assessments will occur for organ function, on days 1, 3, 7 for inflammation, infection, and endothelial injury biomarkers, at baseline for vitamin C level, and at 6 months for mortality and HRQoL. The LOVIT Trial will be conducted in adult general Canadian and international intensive care units. For the PK substudy: Blood samples will be drawn around the 8th dose at time 0 and then after administration at times 1h, 2h, 4h and 6h (the 6h level will be immediately prior to the next dose). The PK substudy will be conducted with 100 participants in 3 of the 25 participating centers.
Relevance. In the context of increasing off-label use of vitamin C for sepsis and ongoing trials of vitamin C bundled with other pharmacological interventions, the LOVIT Trial will constitute a rigorous assessment of the effect of vitamin C monotherapy on patient-important outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Admitted to the intensive care unit with proven or suspected infection as the main diagnosis;
- •Currently treated with a continuous IV infusion of vasopressors (norepinephrine, epinephrine, vasopressin, dopamine, phenylephrine).
排除标准
- •> 24 hours of intensive care unit admission;
- •Known Glucose-6-phosphate dehydrogenase (G6PD) deficiency;
- •Known allergy to vitamin C;
- •Known kidney stones within the past 1 year;
- •Received any intravenous vitamin C during this hospitalization unless incorporated in parenteral nutrition;
- •Expected death or withdrawal of life-sustaining treatments within 48 hours;
- •Previously enrolled in this study;
- •Previously enrolled in a trial with which co-enrolment is not allowed.
- •The LOVIT trial has broad eligibility criteria and includes patients with a primary diagnosis of sepsis of any cause (including sepsis caused by viral pathogens as COVID-19).
研究组 & 干预措施
Vitamin C
Vitamin C: 50 mg/kg every 6 hours for 96 hours.
干预措施: Vitamin C (Drug)
Control
Dextrose 5% in water (D5W) or normal saline (0.9% NaCl) in a volume to match the vitamin C.
干预措施: Control (Other)
结局指标
主要结局
Number of deceased participants or with persistent organ dysfunction
时间窗: Both assessed at 28 days
Defined as death or dependency on mechanical ventilation, renal replacement, or vasopressors
次要结局
- Number of participants with persistent organ dysfunction-free days in intensive care unit(Up to day 28)
- Score of health related quality of life in 6-month survivors(6 months)
- Global tissue dysoxia(Days 1, 3, 7)
- Occurrence of stage 3 acute kidney injury(Up to day 28)
- Acute hemolysis(Up to day 28)
- Hypoglycemia(During the time participants receive the 16 doses of the investigational product and the 7 days following the last dose)
- Vitamin C volume of distribution(8th dose of vitamin C at time 0 (immediately prior to the dose) and then after administration at times 1 hour, 2 hours, 4 hours and 6 hours (Pharmacokynetic substudy))
- Vitamin C clearance(8th dose of vitamin C at time 0 (immediately prior to the dose) and then after administration at times 1 hour, 2 hours, 4 hours and 6 hours (Pharmacokynetic substudy))
- Number of participants deceased at 6 months(6 months)
- Rate of infection(Days 1, 3, 7)
- Rate of endothelial injury(Days 1, 3, 7)
- Organ function (including renal function)(Days 1, 2, 3, 4, 7, 10, 14, 28)
- Rate of inflammation(Days 1, 3, 7)
- Vitamin C plasma concentration(8th dose of vitamin C at time 0 (immediately prior to the dose) and then after administration at times 1 hour, 2 hours, 4 hours and 6 hours (Pharmacokynetic substudy))
研究者
François Lamontagne
Doctor, professor and researcher
Université de Sherbrooke