Vitamin C in Post-cardiac Arrest

NCT03509662 | Completed Phase 2 DMC

• 1 other identifier: NL63681.029.17
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 1

Brief Summary

Only half of the patients suffering from cardiac arrest arrive at the hospital alive. Of these survivors, more than 50% will still die or remain severely disabled. During cardiac arrest ischemia causes damage to the vital organs, especially the brain. When with return of spontaneous circulation oxygen is re-offered to the ischemic organs, massive amounts of reactive oxygen species (ROS) are produced. These ROS can further increase the damage to the myocardium and brain (reperfusion injury). Vitamin C is the primary circulating antioxidant. It scavenges free radicals and reduces the production of ROS. In a recent study we demonstrated that vitamin C plasma levels are deficient in \~60% of the patients after cardiac arrest, probably due to massive consumption. Vitamin C deficiency reduces the protection against oxidative stress. Intravenous supplementation is needed to restore deficiency and the antioxidative effect of vitamin C is much more potent if it is administered in a supraphysiological dose (≥ 3 g per day). Its strong antioxidative effect may reduce damage to the circulation and to brain, heart and other organs. Beneficial effects of high dose i.v. vitamin C after cardiac arrest have been demonstrated in preclinical studies, but not in patients. The investigators hypothesize that vitamin C can reduce organ damage, especially cerebral injury, if administered for a short period as a high i.v. dose during the very early phase of reperfusion after cardiac arrest. Objectives:

• To determine whether an early high dose i.v. vitamin C can improve organ function, especially neurological outcome, in patients after cardiac arrest
• To explore the optimal dosing regimen for high dose i.v. vitamin C
• To investigate in vitro the difference in effect of plasma obtained from post cardiac arrest patients treated with placebo, 3 gr/day or 10 gr/day vitamin C on endothelial cell viability and underlying oxidative pathways.

Conditions

Cardiac Arrest

Keywords

Vitamin C; Cardiac Arrest; Post-cardiac arrest syndrome; Oxidative stress

Outcome Measures

Primary Outcomes (1)

• The delta (Δ) Sequential Organ Failure Assessment (SOFA) score

  ΔSOFA score is defined as the difference between SOFA admission and SOFA at 96 hours (46). Death at 96-hours will be counted as the maximum SOFA score (24 points).

  96 hours

Secondary Outcomes (25)

• Maximal Glasgow Coma Score

  At 96-h and after weaning of sedation

• Cerebral Performance Categories

  At 30 and 180 days

• Modified Rankin Scale

  At 30 and 180 days

• extended Glasgow Outcome Scale

  At 30 and 180 days

• HUI-3 questionnaire

  At 30 and 180 days

Study Arms (3)

Placebo group

PLACEBO COMPARATOR

Group 1 will be treated with placebos for 4 days. All patients will receive Thiamine 200 mg q 12 hourly for 4 days to limit the conversion of vitamin C to oxalate

Drug: Thiamine; Drug: Placebos

Vitamin C - 3 gr/day

ACTIVE COMPARATOR

Group 2 will be treated with 1.5 gr Vitamin C b.i.d. (3 gr/day) for 4 days. All patients will receive Thiamine 200 mg q 12 hourly for 4 days to limit the conversion of vitamin C to oxalate

Drug: Vitamin C; Drug: Thiamine

Vitamin C - 10 gr/day

ACTIVE COMPARATOR

Group 3 will be treated with 5 gr Vitamin C b.i.d. (10 gr/day) for 4 days. All patients will receive Thiamine 200 mg q 12 hourly for 4 days to limit the conversion of vitamin C to oxalate

Drug: Vitamin C; Drug: Thiamine

Interventions

Vitamin C DRUG

Vitamine C will be administered intravenously as ascorbic acid (ascorbinezuur CF 100 mg/ml, Centrafarm BV, Etten Leur, Netherlands).

Also known as: Ascorbic acid

Vitamin C - 10 gr/day; Vitamin C - 3 gr/day

Thiamine DRUG

All patients will receive thiamine 200 mg q 12 hourly for 4 days to limit the conversion of vitamin C to oxalate.

Placebo group; Vitamin C - 10 gr/day; Vitamin C - 3 gr/day

Placebos DRUG

One group receives a placebo.

Placebo group

Eligibility Criteria

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

You may qualify if:

• An out-of-hospital cardiac arrest with return of spontaneous circulation
• Ventricular fibrillation or ventricular tachycardia as first registered cardiac rhythm
• Glasgow Coma Scale (GCS)-score ≤8.

You may not qualify if:

• Patients with pre-existent terminal renal insufficiency
• Known glucose 6-phosphate dehydrogenase deficiency (risk of hemolysis)
• History of urolithiasis, oxalate nephropathy or hemochromatosis
• Treatment limitations.

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• Gelderse Vallei Hospital: collaborator
• Sint Franciscus Gasthuis: collaborator
• Tergooiziekenhuizen: collaborator
• Amphia Hospital: collaborator
• Erasmus Medical Center: collaborator
• Noordwest Ziekenhuisgroep: collaborator
• Maasstad Hospital: collaborator
• OLVG: collaborator

Study Sites (1)

VU Medical Center

Amsterdam, North Holland, 1081 HV, Netherlands

Location

Related Publications (33)

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MeSH Terms

Conditions

Heart Arrest; Post-Cardiac Arrest Syndrome

Interventions

Ascorbic Acid; Thiamine

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Reperfusion Injury; Vascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Angelique ME Spoelstra-de Man, Dr.

  Amsterdam UMC, location VUmc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., Ph.D.

Model Details: In this multicentre, placebo controlled double-blind randomized clinical trial patients will be recruited from the Intensive Care Units of 8 hospitals. 270 comatose patients suffering an out-of-hospital cardiac arrest with ventricular fibrillation/tachycardia as first registered cardiac rhythm and EMV-score ≤8 will be included. As soon as possible patients will be randomly allocated to one of 3 treatment groups of 90 patients each and vitamin C or placebo will be started for 96 hours. Group 1 will be treated with placebo, group 2 with 2 times a day a bolus of 1.5 gr vitamin C and group 3 with 2 times a day a bolus of 5 gr vitamin C. All patients will receive thiamine 200 mg q 12 hourly for 4 days to limit the conversion of vitamin C to oxalate.

Study Record Dates

• First Submitted: February 15, 2018
• First Posted: April 26, 2018
• Study Start: October 7, 2019
• Primary Completion: February 15, 2024
• Study Completion: August 29, 2024
• Last Updated: March 10, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)