Impact of Vitamin C on Biomarkers of Neurologic Injury in Survivors of Cardiac Arrest

NCT04563000 | Unknown Phase 2

• 1 other identifier: VitC
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Out-of-hospital cardiac arrest (OHCA) is one of the leading cause of death in the world. In Slovenia approximately 25% of resuscitated patients survives to discharge from hospitals, usually with poorer functional status. One of key pathophysiological process responsible for poorer functional status is global hypoxic-ischemic injury, which is two-stage. Primary stage occurs immediately after cardiac arrest due to cessation of blood flow. With return of spontaneous circulation a secondary injury occurs, of which the leading process is an imbalance between oxygen delivery and consumption. Reperfusion exposes ischemic tissue to oxygen, resulting in the formation of large amounts of highly reactive oxygen species (ROS) within minutes. ROS lead to oxidative stress, which causes extensive damage to cell structures and leads to cell death. Consequently, necrosis and apoptosis are responsible for organ dysfunction and functional outcome of these patients. Such injury of neural tissue causes brain damage, which is ultimately responsible for poor neurological and thus functional outcome of OHCA survivors. The extent of brain damage can be determined in several ways: clinically by assessing quantitative and qualitative consciousness and the presence of involuntary movements in an unconscious patient, by assessing activity on electroencephalographic record, by imaging of the brain with computed tomography and magnetic resonance imaging, as well as by assessing levels of biological markers of brain injury. Of the latter, the S-100b protein and neuron-specific enolase have been shown to be suitable for such assessment. Oxidative stress is counteracted by the body with endogenous antioxidants that balance excess free radicals and stabilize cellular function. Vitamin C (ascorbic acid) is the body's main antioxidant and is primarily consumed during oxidative stress. Large amounts of ROS rapidly depletes the body's vitamin C stores. Humans cannot synthesise vitamin C and enteral uptake of vitamin C is limited by transporter saturation. On the other hand, parenteral (venous) dosing of vitamin C can achieve concentrations of vitamin C above physiological and thus produce a stronger antioxidant effect. The beneficial effect of parenteral dosing of vitamin C has been establish in several preclinical and clinical studies in patients with ischemic stroke and cardiac arrest. The investigators hypothesize that there is a similarly beneficial effect of vitamin C in survivors of OHCA.

Conditions

Heart Arrest, Out-Of-Hospital; Biomarkers; Oxidative Stress; Neurological Injury

Keywords

vitamin C; biomarkers; brain injury; cardiac arrest

Outcome Measures

Primary Outcomes (1)

• Biomarkers of neurological injury

  Serum levels of protein S-100b and neuron-specific enolase.

  5th day

Secondary Outcomes (19)

• Brain imaging (CT and MRI)

  3rd-10th day

• Electroencephalography (EEG)

  3rd-10th day

• Evaluation of pupils

  from admission until 14 days or till discharge from ICU or death (whatever comes first)

• Evaluation of involuntary movements

  from admission until 14 days or till discharge from ICU or death (whatever comes first)

• Evaluation of GCS

  from admission until 14 days or till discharge from ICU or death (whatever comes first)

Study Arms (2)

Vitamin C

EXPERIMENTAL

Group of patients that will receive vitamin C (ascorbic acid 1,5 g mixed with 0,9 % solution of sodium chloride 100 ml every 12 hours for 4 days intravenously).

Drug: Vitamin C

Placebo

PLACEBO COMPARATOR

Group of patients that will receive placebo (0,9 % solution of sodium chloride 100 ml every 12 hours for 4 days intravenously).

Drug: Placebo

Interventions

Vitamin C DRUG

Ascorbic acid 1,5 g intravenously every 12-hours for 4 consecutive days

Vitamin C

Placebo DRUG

0,9 % solution of sodium chloride 100 ml intravenously every 12-hours for 4 consecutive days

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- comatose survivors of out-of-hospital arrest

You may not qualify if:

• patients with trauma, asphyxia, drowning or electrocution as a cause of cardiac arrest
• history of oxalate nephropathy or nephrolithiasis, glucose-6-phosphate dehydrogenase deficiency, and hemochromatosis
• pregnancy

Sponsors & Collaborators

• University Medical Centre Maribor: lead

Study Sites (1)

University Medical Centre Maribor

Maribor, 2000, Slovenia

Location

Related Publications (17)

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  PMID: 27321577 BACKGROUND

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  PMID: 18963350 BACKGROUND

• Sekhon MS, Ainslie PN, Griesdale DE. Clinical pathophysiology of hypoxic ischemic brain injury after cardiac arrest: a "two-hit" model. Crit Care. 2017 Apr 13;21(1):90. doi: 10.1186/s13054-017-1670-9.

  PMID: 28403909 BACKGROUND

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  PMID: 19535196 BACKGROUND

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  PMID: 22332036 BACKGROUND

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  PMID: 21953354 BACKGROUND

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MeSH Terms

Conditions

Out-of-Hospital Cardiac Arrest; Trauma, Nervous System; Brain Injuries; Heart Arrest

Interventions

Ascorbic Acid

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Wounds and Injuries; Brain Diseases; Central Nervous System Diseases; Craniocerebral Trauma

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Study Officials

• Andrej Markota, MD, PhD, Assist. Prof.

  University Medical Centre Maribor

  STUDY CHAIR

Central Study Contacts

Andrej Markota, MD, PhD, Assist. Prof.

CONTACT

+38651311519; andrej.markota@ukc-mb.si

Matevž Privšek, MD

CONTACT

+38640642986; matevz.privsek@icloud.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2020
• First Posted: September 24, 2020
• Study Start: October 1, 2020
• Primary Completion: October 31, 2022
• Study Completion: December 31, 2022
• Last Updated: September 24, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

SL (1)