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

Out-Of-Hospital Cardiac Arrest Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04921189
• Other study ID #: STAR trial
• Status: Recruiting
• Phase: Phase 2
• Start date: December 31, 2021
• Est. completion date: December 31, 2023

Study information

• Verified date: August 2023
• Source: Asan Medical Center
• Contact: Youn-Jung Kim, PhD
• Phone: 821030100329
• Email: yjkim.em[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 79 Years

Eligibility

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).

Related Conditions & MeSH terms

• Heart Arrest
• Out-of-Hospital Cardiac Arrest
• Post-Cardiac Arrest Syndrome

Intervention

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

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul

Sponsors (9)

Lead Sponsor	Collaborator
Asan Medical Center	Chung-Ang University, Ewha Womans University, Hanil General Hospital, Hanyang University, Samsung Changwon Hospital, Samsung Medical Center, Seoul St. Mary's Hospital, Wonju Severance Christian Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	48 to 72 hours
Secondary	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.	at 48, 72 hours
Secondary	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).	at 24, 48, 72 hours
Secondary	30-day Mortality	All-cause death within 30 days	30 days
Secondary	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.	30 days
Secondary	In-hospital mortality	All-cause death during hospitalization	1 year
Secondary	Intensive Care Unit (ICU) stay	1 year	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 ?rst day of admission.
Secondary	7-day mortality	All-cause death within 7 days	7 days
Secondary	90-day mortality	All-cause death within 90 days	90 days
Secondary	180-day mortality	All-cause death within 180 days	180 days
Secondary	Time to Awakening	Days to neurological recovery, defined as Glasgow Outcome Scale > 13 from cardiac arrest	30 days
Secondary	ICU free day	Days in general ward transferred from ICU within 14 days from admission	14 days
Secondary	Hospital stay	The total hospitalization days	1 year
Secondary	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.	at 30, 90, 180 days
Secondary	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.	at 30, 90, 180 days