- ICH GCP
- US Clinical Trials Registry
- Clinical Trial 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
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.
Study Overview
Status
Intervention / Treatment
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 Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Youn-Jung Kim, PhD
- Phone Number: 821030100329
- Email: yjkim.em@gmail.com
Study Locations
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Seoul, Korea, Republic of, 05505
- Recruiting
- Asan Medical Center
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Contact:
- Youn-Jung Kim, PhD
- Phone Number: 82230100329
- Email: yjkim.em@gmail.com
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Sub-Investigator:
- Won Young Kim, PhD
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Principal Investigator:
- Youn-Jung Kim, Phd
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: 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.
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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.
Other Names:
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Placebo Comparator: Placebo
An identical volume of 0.9% saline (150mL) administered through intravenous infusion over 60 min every 12 h for 3 days.
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An identical volume of 0.9% saline (150mL) administered through intravenous infusion over 60 min every 12 h for 3 days.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
the peak neuron-specific enolase level
Time Frame: 48 to 72 hours
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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.
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48 to 72 hours
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
the delta neuron-specific enolase (NSE) level
Time Frame: at 48, 72 hours
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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.
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at 48, 72 hours
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The delta Sequential Organ Failure Assessment (SOFA) score
Time Frame: at 24, 48, 72 hours
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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).
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at 24, 48, 72 hours
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30-day Mortality
Time Frame: 30 days
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All-cause death within 30 days
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30 days
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Time to death
Time Frame: 30 days
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The time to death is defined as the duration of survival within 30 days.
Survival after 30 days will be counted as 30.
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30 days
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In-hospital mortality
Time Frame: 1 year
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All-cause death during hospitalization
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1 year
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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.
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1 year
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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.
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7-day mortality
Time Frame: 7 days
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All-cause death within 7 days
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7 days
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90-day mortality
Time Frame: 90 days
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All-cause death within 90 days
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90 days
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180-day mortality
Time Frame: 180 days
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All-cause death within 180 days
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180 days
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Time to Awakening
Time Frame: 30 days
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Days to neurological recovery, defined as Glasgow Outcome Scale > 13 from cardiac arrest
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30 days
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ICU free day
Time Frame: 14 days
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Days in general ward transferred from ICU within 14 days from admission
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14 days
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Hospital stay
Time Frame: 1 year
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The total hospitalization days
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1 year
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Neurological outcome assessed using Cerebral Performance Category score
Time Frame: at 30, 90, 180 days
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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.
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at 30, 90, 180 days
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Neurological outcome assessed using the modified Rankin Scale
Time Frame: at 30, 90, 180 days
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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.
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at 30, 90, 180 days
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Won Young Kim, PhD, A
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Heart Diseases
- Cardiovascular Diseases
- Vascular Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Postoperative Complications
- Brain Injuries
- Reperfusion Injury
- Heart Arrest
- Out-of-Hospital Cardiac Arrest
- Post-Cardiac Arrest Syndrome
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Inflammatory Agents
- Protective Agents
- Micronutrients
- Vitamins
- Antioxidants
- Vitamin B Complex
- Hydrocortisone
- Ascorbic Acid
- Thiamine
Other Study ID Numbers
- STAR trial
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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