NCT04921189

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

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 160 (actual)
• Sponsor: Asan Medical Center · Academic / Other
• Sex: All
• Age: 19 Years – 79 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed 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.

Conditions

• Out-Of-Hospital Cardiac Arrest
• Postcardiac Arrest Syndrome

Interventions

Type	Name	Description
DRUG	The combined supplement of Ascorbic acid, Thiamine, and Cortisol	The combined administration of 3 drugs will be mixed in a 50 mL 0.9% saline bag respectively and administered through intravenous infusion over 60 min every 12 h for 3 days. 1. Ascorbic acid (Ascorbic acid Inj \[500mg\]®): 50 mg/kg, maximum single dose 3 g, daily dose 6 g 2. Thiamine (Thiamine hcl inj \[50mg\]®): 200 mg 3. Cortisol (Cortisolu inj \[100mg\]®): 100mg (The main exposure was corticosteroid therapy, defined as the use of systemic corticosteroids. But if unavailable, it could be converted to hydrocortisone-equivalent doses (methylprednisolone 1:5, dexamethasone 1:25, prednisolone 1:4).)
DRUG	Placebo	An identical volume of 0.9% saline (150mL) administered through intravenous infusion over 60 min every 12 h for 3 days.

Timeline

• Start date: 2021-12-31
• Primary completion: 2024-12-10
• Completion: 2025-06-09
• First posted: 2021-06-10
• Last updated: 2025-06-11

Locations

1 site across 1 country: South Korea