Vitamin C in Post-cardiac Arrest

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

Interventions

DRUG

Vitamin C

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

DRUG

Thiamine

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

DRUG

Placebos

One group receives a placebo.

Sponsors & Collaborators

• Gelderse Vallei Hospital

  collaborator OTHER

• Sint Franciscus Gasthuis

  collaborator OTHER

• Tergooiziekenhuizen

  collaborator UNKNOWN

• Amphia Hospital

  collaborator OTHER

• Erasmus Medical Center

  collaborator OTHER

• Noordwest Ziekenhuisgroep

  collaborator OTHER

• Maasstad Hospital

  collaborator OTHER

• OLVG

  collaborator NETWORK

• Amsterdam UMC, location VUmc

  lead OTHER

Principal Investigators

• Angelique ME Spoelstra-de Man, Dr. · Amsterdam UMC, location VUmc

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-10-07

Primary Completion

2024-02-15

Completion

2024-08-29

Countries

• Netherlands

Study Locations