Out-Of-Hospital Cardiac ArrestPhase 2NCT04921189
Steroid, Thiamine and Ascorbic Acid for Comatose Out-of-hospital Cardiac Arrest Survivors
A Phase 2 study testing The combined supplement of Ascorbic acid, Thiamine, and Cortisol in people with Out-Of-Hospital Cardiac Arrest and Postcardiac Arrest Syndrome, run by Asan Medical Center at 1 site in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 to 79 years
- Conditions the study is for
- Out-Of-Hospital Cardiac Arrest, Postcardiac Arrest Syndrome
- What is being tested?
- The combined supplement of Ascorbic acid, Thiamine, and Cortisol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 1 siteSouth Korea
- Study dates
- 31 Dec 2021to 9 Jun 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- An out-of-hospital cardiac arrest survivors treated with targeted temperature management (target between 32 and 36 °C)
- Presumed cardiogenic cause as cardiac arrest
Who cannot join
- > 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
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- 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 locations and contacts
1 site in 1 country.
About this study
Official title: 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
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.
Read the 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.
- Being tested
- The combined supplement of Ascorbic acid, Thiamine, and Cortisol, Placebo
- Keywords
- Postcardiac Arrest Syndrome, Ischemia/reperfusion injury, Neuron-specific enolase, Ascorbic acid, Thiamine, Cortisol
- Medical subject headings
- Out-of-Hospital Cardiac Arrest, Post-Cardiac Arrest Syndrome, Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
The combined supplement of Ascorbic acid, Thiamine, and CortisolDrug
Also called Ascorbic acid, Thiamine hcl, Cortisolu
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.
- Ascorbic acid (Ascorbic acid Inj [500mg]®): 50 mg/kg, maximum single dose 3 g, daily dose 6 g
- Thiamine (Thiamine hcl inj [50mg]®): 200 mg
- 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).)
PlaceboDrug
Also called Normal saline
An identical volume of 0.9% saline (150mL) administered through intravenous infusion over 60 min every 12 h for 3 days.
| Study group | Role | What they receive |
|---|---|---|
| The combined supplement of Ascorbic acid, Thiamine, and Cortisol | Active comparator | 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. Receives: Drug: The combined supplement of Ascorbic acid, Thiamine, and Cortisol |
| Placebo | Placebo comparator | An identical volume of 0.9% saline (150mL) administered through intravenous infusion over 60 min every 12 h for 3 days. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
the peak neuron-specific enolase level
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.
Measured: 48 to 72 hours
Secondary outcomes (14)
the delta neuron-specific enolase (NSE) level
The delta NSE level is defined as the difference between NSE at 24 hours and the peak NSE between 48 and 72 hours after cardiac arrest.
Measured: at 48, 72 hours
The delta Sequential Organ Failure Assessment (SOFA) score
The delta SOFA is defined as the difference between SOFA admission and SOFA at 72 hours after cardiac arrest. Death within 72 hours will be counted as the maximum SOFA score (24).
Measured: at 24, 48, 72 hours
30-day Mortality
All-cause death within 30 days
Measured: 30 days
Time to death
The time to death is defined as the duration of survival within 30 days. Survival after 30 days will be counted as 30.
Measured: 30 days
In-hospital mortality
All-cause death during hospitalization
Measured: 1 year
Intensive Care Unit (ICU) stay
1 year
Measured: 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.
7-day mortality
All-cause death within 7 days
Measured: 7 days
90-day mortality
All-cause death within 90 days
Measured: 90 days
180-day mortality
All-cause death within 180 days
Measured: 180 days
Time to Awakening
Days to neurological recovery, defined as Glasgow Outcome Scale > 13 from cardiac arrest
Measured: 30 days
ICU free day
Days in general ward transferred from ICU within 14 days from admission
Measured: 14 days
Hospital stay
The total hospitalization days
Measured: 1 year
Neurological outcome assessed using Cerebral Performance Category score
Cerebral Performance Category (CPC) score is defined as follows: CPC 1, Good cerebral performance (normal life); CPC 2, Moderate cerebral disability (disability but independent); CPC 3, Severe cerebral disability (conscious but disabled and dependent); CPC 4, Coma or vegetative state (unconscious); CPC 5, Brain death.
Measured: at 30, 90, 180 days
Neurological outcome assessed using the modified Rankin Scale
The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale runs from 0-6, running from perfect health without symptoms to death. 0 - No symptoms.
- - No significant disability. Able to carry out all usual activities, despite some symptoms.
- - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
- - Moderate disability. Requires some help, but able to walk unassisted.
- - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
- - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
- - Dead.
Measured: at 30, 90, 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2021
- Study start31 Dec 2021
- Primary completion10 Dec 2024
- Study completion9 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Out-Of-Hospital Cardiac ArrestStudies of the same condition, open and under way.
- More trials run by Asan Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 160 participants (actual)
Sponsor and investigators
- Lead sponsor
- Asan Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Seoul St. Mary's Hospital, Wonju Severance Christian Hospital, Samsung Changwon Hospital, Samsung Medical Center, Chung-Ang University, Hanyang University, Ewha Womans University, Hanil General Hospital
- Responsible party
- Principal investigator, Won Young Kim, Asan Medical Center
- Investigators
- Won Young Kim, PhD, Study chair, A
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04921189
- Sponsor's protocol ID
- STAR trial
- Status last verified
- Jun 2025
- First submitted
- 4 Jun 2021
- Last updated
- 11 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kim YJ, Ko BS, Roh YI, Kwon HJ, Kim S, Cha KC, Kim YH, Kim WY. Steroid, thiamine, and ascorbic acid for comatose out-of-hospital cardiac arrest survivors (STAR): a randomised, placebo-controlled, phase 2 trial. EClinicalMedicine. 2026 Sep 5;100:104191. doi: 10.1016/j.eclinm.2026.104191. eCollection 2026 Oct.
PubMed 42733931Kim 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.
PubMed 40215244
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04921189
- Acronym / sponsor ID
- STAR trial
- Keywords
- Postcardiac Arrest Syndrome, Ischemia/reperfusion injury, Neuron-specific enolase, Ascorbic acid, Thiamine, Cortisol
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 160 participants (actual)
- Lead sponsor
- Asan Medical CenterUniversity, hospital or other
- Collaborators
- Seoul St. Mary's Hospital, Wonju Severance Christian Hospital, Samsung Changwon Hospital, Samsung Medical Center, Chung-Ang University, Hanyang University, Ewha Womans University, Hanil General Hospital
- Study start
- 31 Dec 2021 (actual)
- Primary completion
- 10 Dec 2024 (actual)
- Study completion
- 9 Jun 2025 (actual)
- First posted
- 10 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| The combined supplement of Ascorbic acid, Thiamine, and Cortisol | Active comparator | Drug: The combined supplement of Ascorbic acid, Thiamine, and CortisolThe 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. |
| Placebo | Placebo comparator | Drug: PlaceboAn identical volume of 0.9% saline (150mL) administered through intravenous infusion over 60 min every 12 h for 3 days. |
Who may qualify
- Ages
- 19 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- An out-of-hospital cardiac arrest survivors treated with targeted temperature management (target between 32 and 36 °C)
- Presumed cardiogenic cause as cardiac arrest
Key exclusion criteria (15 listed)
- > 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| The combined supplement of Ascorbic acid, Thiamine, and CortisolAlso: Ascorbic acid, Thiamine hcl, CortisoluThe 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 | The combined supplement of Ascorbic acid, Thiamine, and Cortisol |
| PlaceboAlso: Normal salineAn identical volume of 0.9% saline (150mL) administered through intravenous infusion over 60 min every 12 h for 3 days. | Drug | Placebo |
Primary outcome
the peak neuron-specific enolase level
Time frame: 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.
14 secondary outcomes
the delta neuron-specific enolase (NSE) level
Time frame: at 48, 72 hours
The delta Sequential Organ Failure Assessment (SOFA) score
Time frame: at 24, 48, 72 hours
30-day Mortality
Time frame: 30 days
Time to death
Time frame: 30 days
In-hospital mortality
Time frame: 1 year
Intensive Care Unit (ICU) stay
Time frame: 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.
7-day mortality
Time frame: 7 days
90-day mortality
Time frame: 90 days
180-day mortality
Time frame: 180 days
Time to Awakening
Time frame: 30 days
ICU free day
Time frame: 14 days
Hospital stay
Time frame: 1 year
Neurological outcome assessed using Cerebral Performance Category score
Time frame: at 30, 90, 180 days
Neurological outcome assessed using the modified Rankin Scale
Time frame: at 30, 90, 180 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2025.
- Derived from this study: PubMed 42733931Kim YJ, Ko BS, Roh YI, Kwon HJ, Kim S, Cha KC, Kim YH, Kim WY. Steroid, thiamine, and ascorbic acid for comatose out-of-hospital cardiac arrest survivors (STAR): a randomised, placebo-controlled, phase 2 trial. EClinicalMedicine. 2026 Sep 5;100:104191. doi: 10.1016/j.eclinm.2026.104191. eCollection 2026 Oct.
- Derived from this study: PubMed 40215244Kim 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Won Young Kim, PhD study chair
A
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing The combined supplement of Ascorbic acid, Thiamine, and Cortisol in people with Out-Of-Hospital Cardiac Arrest and Postcardiac Arrest Syndrome, run by Asan Medical Center at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the peak neuron-specific enolase level (time frame: 48 to 72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04921189, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2025.