Clinical trial NCT04921189: Steroid, Thiamine and Ascorbic Acid for Comatose Out-of-hospital Cardiac Arrest Survivors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Out-Of-Hospital Cardiac Arrest
Postcardiac Arrest Syndrome
Keywords: Postcardiac Arrest Syndrome
Ischemia/reperfusion injury
Neuron-specific enolase
Ascorbic acid
Thiamine
Cortisol
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: Seoul St. Mary's Hospital
name: Wonju Severance Christian Hospital
name: Samsung Changwon Hospital
name: Samsung Medical Center
name: Chung-Ang University
name: Hanyang University
name: Ewha Womans University
name: Hanil General Hospital
First posted: 2021-06-10
Enrollment: 160
Sex: ALL
Minimum age (years): 19
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: the peak neuron-specific enolase level
timeFrame: 48 to 72 hours
Secondary outcomes:
measure: the delta neuron-specific enolase (NSE) level
timeFrame: at 48, 72 hours
measure: The delta Sequential Organ Failure Assessment (SOFA) score
timeFrame: at 24, 48, 72 hours
measure: 30-day Mortality
timeFrame: 30 days
measure: Time to death
timeFrame: 30 days
measure: In-hospital mortality
timeFrame: 1 year
measure: Intensive Care Unit (ICU) stay
timeFrame: 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.
measure: 7-day mortality
timeFrame: 7 days
measure: 90-day mortality
timeFrame: 90 days
measure: 180-day mortality
timeFrame: 180 days
measure: Time to Awakening
timeFrame: 30 days
measure: ICU free day
timeFrame: 14 days
measure: Hospital stay
timeFrame: 1 year
measure: Neurological outcome assessed using Cerebral Performance Category score
timeFrame: at 30, 90, 180 days
measure: Neurological outcome assessed using the modified Rankin Scale
timeFrame: at 30, 90, 180 days
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
affiliation: A
name: Won Young Kim, PhD
role: STUDY_CHAIR
References: