Steroid, Thiamine and Ascorbic Acid for Comatose Out-of-hospital Cardiac Arrest Survivors

Asan Medical Center

Status and phase: Completed; Phase 2

Conditions: Out-Of-Hospital Cardiac Arrest; Postcardiac Arrest Syndrome

Treatments: Drug: The combined supplement of Ascorbic acid, Thiamine, and Cortisol; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT04921189

STAR trial

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 160 patients

Sex: All

Ages: 19 to 79 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• An out-of-hospital cardiac arrest survivors treated with targeted temperature management (target between 32 and 36 °C)
• Presumed cardiogenic cause as cardiac arrest

Exclusion criteria

• > 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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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160 participants in 2 patient groups, including a placebo group

The combined supplement of Ascorbic acid, Thiamine, and Cortisol

Active Comparator group

Description:

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.

Treatment:

Drug: The combined supplement of Ascorbic acid, Thiamine, and Cortisol

Placebo

Placebo Comparator group

Description:

An identical volume of 0.9% saline (150mL) administered through intravenous infusion over 60 min every 12 h for 3 days.

Treatment:

Drug: Placebo