Steroid, Thiamine and Ascorbic Acid During Post-Resuscitation Period for Comatose Out-of-hospital Cardiac Arrest Survivors (STAR) Trial: Multi-center, Randomized, Single-blinded, Controlled Pilot Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- the peak neuron-specific enolase level
研究概览
简要总结
The mortality and neurological outcomes among out-of-hospital cardiac arrest survivors have not improved despite the medical advances. The whole body ischemia/reperfusion injuries after cardiac arrest mainly damaged the brain. To improve the neurologic outcome among those patients, additional interventions would be warranted.
The investigators hypothesize that the combined use of cortisol, ascorbic acid (vitamin C), and thiamine during the early post-resuscitation period would attenuate the whole-body ischemia/reperfusion injuries among the out-of-hospital cardiac arrest survivors treated with targeted temperature management.
详细描述
The mortality and neurological outcomes among the out-of-hospital cardiac arrest survivors are still dismal. In addition, the metabolic and oxidative stress can persist or even worsen at the cellular level after resuscitation, and these whole-body ischemia/reperfusion injuries contribute to multiple organ failure, known as the post-cardiac arrest syndrome. Therefore, additional interventions to reduces the injuries would be warranted.
Cortisol has beneficial antioxidant and anti-apoptotic properties and stabilizes cellular membranes exposed to oxidative stress. It also maintains hemodynamic stability and improves organ function by reducing ischemia/reperfusion injuries.
Thiamine is a cofactor that acts on enzymes essential for glucose metabolism, the generation of adenosine triphosphate, and nicotinamide adenine dinucleotide phosphate production. It assists the cellular metabolisms and attenuates the potential adverse effect of ascorbic acid (vitamin C) by preventing the conversion of ascorbic acid into oxalate. Ascorbic acid is a well-known antioxidant and has anti-inflammatory effects. It acted as an antioxidant defense substance, reducing reactive oxygen species and reactive nitrogen species and improving microcirculation by limiting oxidative injury and endothelial barrier disruption. The theoretical and experimental studies suggested the concomitant use of cortisol, thiamine, and ascorbic acid might have potential treatment synergism for whole-body ischemia/reperfusion injuries after cardiac arrest.
The investigators hypothesize that their combined use during the early post-resuscitation period will reduce the whole-body ischemia/reperfusion injuries, especially the brain, in out-of-hospital cardiac arrest survivors treated with targeted temperature management.
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
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 19 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •An out-of-hospital cardiac arrest survivors treated with targeted temperature management (target between 32 and 36 °C)
- •Presumed cardiogenic cause as cardiac arrest
排除标准
- •> 12 hours from cardiac arrest to drug or placebo administration
- •previous poor neurological status (Cerebral Performance Categories 3 to 5)
- •patients who have set limitations on treatment (e.g. patients with a signed do-not-resuscitate order)
- •Patients with an underlying terminal-stage disease without an active treatment plan and those who are not expected to survive to discharge
- •patients taking at least 1 g/day of vitamin C or receiving intravenous thiamine prior to enrolment
- •patients experiencing cardiac arrest prior to enrolment or who are expected to die within 24 h despite best possible treatment, based on the judgement of medical personnel
- •pregnant women
- •patients with glucose-6-phosphate dehydrogenase deficiency
- •patients with a history of hypersensitivity reactions to the trial drugs
- •patients with thalassemia
- •patients with hyperoxaluria
- •patients with cystinuria
- •patients with ongoing gout attacks
- •patients diagnosed with oxalate renal stones
- •patients who do not voluntarily consent to participate in the trial (directly or by legal proxy).
研究组 & 干预措施
The combined supplement of Ascorbic acid, Thiamine, and Cortisol
The combined administration of 3 drugs will be administered through intravenous infusion over 60 min every 12 h for 3 days for the out-of-hospital cardiac arrest survivors treated with targeted temperature management.
干预措施: The combined supplement of Ascorbic acid, Thiamine, and Cortisol (Drug)
Placebo
An identical volume of 0.9% saline (150mL) administered through intravenous infusion over 60 min every 12 h for 3 days.
干预措施: Placebo (Drug)
结局指标
主要结局
the peak neuron-specific enolase level
时间窗: 48 to 72 hours
Serum Neuron-Specific Enolase (NSE) level at 48 to 72 hours after resuscitation will measured by enzyme immunoassay, respectively. We will use the peak neuron-specific enolase level.
次要结局
- Time to death(30 days)
- 90-day mortality(90 days)
- the delta neuron-specific enolase (NSE) level(at 48, 72 hours)
- The delta Sequential Organ Failure Assessment (SOFA) score(at 24, 48, 72 hours)
- 30-day Mortality(30 days)
- 7-day mortality(7 days)
- Time to Awakening(30 days)
- ICU free day(14 days)
- In-hospital mortality(1 year)
- Hospital stay(1 year)
- Neurological outcome assessed using the modified Rankin Scale(at 30, 90, 180 days)
- Intensive Care Unit (ICU) stay(The total length of ICU stay will be determined from the date of ICU admission until the patient is discharged from the Intensive Care Unit or the date of death from any cause, assessed up to 1 year after the first day of admission.)
- 180-day mortality(180 days)
- Neurological outcome assessed using Cerebral Performance Category score(at 30, 90, 180 days)
研究者
Won Young Kim
Professor
Asan Medical Center