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

September 21, 2020 updated by: University Medical Centre Maribor

Impact of Vitamin C on Biomarkers of Neurologic Injury in Patients With Return of Spontaneous Circulation After Out-of-Hospital Cardiac Arrest

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

150

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Slovenia
      • Maribor, Slovenia, 2000
        • University Medical Centre Maribor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

- comatose survivors of out-of-hospital arrest

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Vitamin C
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
Ascorbic acid 1,5 g intravenously every 12-hours for 4 consecutive days
Placebo Comparator: Placebo
Group of patients that will receive placebo (0,9 % solution of sodium chloride 100 ml every 12 hours for 4 days intravenously).
Drug: Placebo
0,9 % solution of sodium chloride 100 ml intravenously every 12-hours for 4 consecutive days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Biomarkers of neurological injury
Time Frame: 5th day
Serum levels of protein S-100b and neuron-specific enolase.
5th day

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Brain imaging (CT and MRI)
Time Frame: 3rd-10th day
Unconscious survivors will have first brain imaging on the 3rd day, if still unconscious, second imaging around the 10th day. Imaging results will be descriptive (normal or pathological with signs of global ischemic injury: generalised edema, reduced grey and white matter differentiation, obliteration of the sulci). Second image will be compared to the first.
3rd-10th day
Electroencephalography (EEG)
Time Frame: 3rd-10th day
Unconscious survivors will have first EEG on the 3rd day, if still unconscious, second imaging around the 10th day. EEG results will be descriptive (normal or pathological with background suppression with or without periods of bursts, with or without response to external stimulus and similar patterns). Second EEG will be compared to the first.
3rd-10th day
Evaluation of pupils
Time Frame: from admission until 14 days or till discharge from ICU or death (whatever comes first)
Pupils size, reactivity and symmetry on admission and during hospitalisation will be observed daily.
from admission until 14 days or till discharge from ICU or death (whatever comes first)
Evaluation of involuntary movements
Time Frame: from admission until 14 days or till discharge from ICU or death (whatever comes first)
The presence of involuntary movements will be observed daily.
from admission until 14 days or till discharge from ICU or death (whatever comes first)
Evaluation of GCS
Time Frame: from admission until 14 days or till discharge from ICU or death (whatever comes first)
Level of consciousness will be determined daily with Glasgow Coma Scale (GCS).
from admission until 14 days or till discharge from ICU or death (whatever comes first)
Evaluation of FOUR
Time Frame: from admission until 14 days or till discharge from ICU or death (whatever comes first)
Level of consciousness will be determined daily with Full Outline of UnResponsiveness (FOUR) score.
from admission until 14 days or till discharge from ICU or death (whatever comes first)
Cerebral Performance Category
Time Frame: from admission till discharge from ICU or death (whatever comes first)
Cerebral Performance Category (CPC) at discharge will be recorded.
from admission till discharge from ICU or death (whatever comes first)
Left ventricular ejection fraction
Time Frame: from admission until 14 days or till discharge from ICU or death (whatever comes first)
Left ventricular ejection fraction (first, last, best, worst), determined by ultrasound will be noted.
from admission until 14 days or till discharge from ICU or death (whatever comes first)
Arrhythmias
Time Frame: from admission until 14 days or till discharge from ICU or death (whatever comes first)
Presence of arrhythmias and the need for treating them will be recorded.
from admission until 14 days or till discharge from ICU or death (whatever comes first)
Evaluation of heart failure
Time Frame: from admission until 14 days or till discharge from ICU or death (whatever comes first)
Clinical evaluation of heart failure according to Killip-Kimball classification will be performed (worst result).
from admission until 14 days or till discharge from ICU or death (whatever comes first)
Serum troponin level
Time Frame: from admission until 14 days or till discharge from ICU or death (whatever comes first)
Serum troponin levels will be determined (on admission, minimal, maximal).
from admission until 14 days or till discharge from ICU or death (whatever comes first)
Serum Brain natriuretic peptide
Time Frame: from admission until 14 days or till discharge from ICU or death (whatever comes first)
Serum brain natriuretic peptide levels will be determined (on admission, minimal, maximal).
from admission until 14 days or till discharge from ICU or death (whatever comes first)
Vasopressor and/or inotrope need
Time Frame: from admission until 14 days or till discharge from ICU or death (whatever comes first)
The need for vasopressors and inotropes will be noted, along with the name of the substance, maximal dosage and duration.
from admission until 14 days or till discharge from ICU or death (whatever comes first)
Mechanical ventilation
Time Frame: from admission until 14 days or till discharge from ICU or death (whatever comes first)
Days and hours of mechanical ventilation will be noted.
from admission until 14 days or till discharge from ICU or death (whatever comes first)
Kidney failure
Time Frame: from admission until 14 days or till discharge from ICU or death (whatever comes first)
The need for renal replacement therapy (and consecutive day of such therapy) will be recorded.
from admission until 14 days or till discharge from ICU or death (whatever comes first)
Serum urea levels
Time Frame: from admission until 14 days or till discharge from ICU or death (whatever comes first)
Serum levels of urea will be recorded (on admission, minimal, maximal).
from admission until 14 days or till discharge from ICU or death (whatever comes first)
Serum creatinine levels
Time Frame: from admission until 14 days or till discharge from ICU or death (whatever comes first)
Serum creatinine levels will be recorded (on admission, minimal, maximal).
from admission until 14 days or till discharge from ICU or death (whatever comes first)
Serum C-reactive protein levels
Time Frame: from admission until 14 days or till discharge from ICU or death (whatever comes first)
Serum C-reactive protein levels will be determined (on admission, minimal, maximal).
from admission until 14 days or till discharge from ICU or death (whatever comes first)
Serum procalcitonin levels
Time Frame: from admission until 14 days or till discharge from ICU or death (whatever comes first)
Serum procalcitonin levels will be determined (on admission, minimal, maximal).
from admission until 14 days or till discharge from ICU or death (whatever comes first)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Centre Maribor

Investigators

  • Study Chair: Andrej Markota, MD, PhD, Assist. Prof., University Medical Centre Maribor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

October 1, 2020

Primary Completion (Anticipated)

October 31, 2022

Study Completion (Anticipated)

December 31, 2022

Study Registration Dates

First Submitted

September 10, 2020

First Submitted That Met QC Criteria

September 21, 2020

First Posted (Actual)

September 24, 2020

Study Record Updates

Last Update Posted (Actual)

September 24, 2020

Last Update Submitted That Met QC Criteria

September 21, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VitC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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