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

NCT ID: NCT04921189

Last Updated: 2025-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-31
• Study Completion Date: 2025-06-09

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

The combined supplement of Ascorbic acid, Thiamine, and Cortisol

Intervention Type: DRUG

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).)

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

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).)

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

Ascorbic acid; Thiamine hcl; Cortisolu; Normal saline

Eligibility Criteria

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).

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Seoul St. Mary's Hospital

OTHER

Sponsor Role: collaborator

Wonju Severance Christian Hospital

OTHER

Sponsor Role: collaborator

Samsung Changwon Hospital

OTHER

Sponsor Role: collaborator

Samsung Medical Center

OTHER

Sponsor Role: collaborator

Chung-Ang University

OTHER

Sponsor Role: collaborator

Hanyang University

OTHER

Sponsor Role: collaborator

Ewha Womans University

OTHER

Sponsor Role: collaborator

Hanil General Hospital

UNKNOWN

Sponsor Role: collaborator

Asan Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Won Young Kim

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Won Young Kim, PhD

Role: STUDY_CHAIR

A

Locations

Asan Medical Center

Seoul, , South Korea

Countries

South Korea

References

Kim YJ, Ko BS, Roh YI, Kim YH, Kim WY. Steroid, thiamine, and ascorbic acid during post-resuscitation period for comatose out-of-hospital cardiac arrest survivors (STAR) trial: Protocol for a clinical trial. PLoS One. 2025 Apr 11;20(4):e0319733. doi: 10.1371/journal.pone.0319733. eCollection 2025.

Reference Type: DERIVED

PMID: 40215244 (View on PubMed)

Other Identifiers

STAR trial

Identifier Type: -

Identifier Source: org_study_id