Selenium to Improve Neurological Outcome After Cardiac Arrest (SCPR)

Effect of High Dose Selenium on Inflammation and Neurological Outcome After Cardiac Arrest: A Randomized, Double Blind Placebo Controlled Phase 2a Study

After cardiac arrest and successful resuscitation it can happen that the brain function of a patient is impaired because the brain was without oxygen for a prolonged period of time. Several strategies have been studied to improve brain function after cardiac arrest. Cooling of the patients is routinely used today. The trace element selenium has several biological functions and is important for defense mechanisms against oxidative stress, which occurs after cardiac arrest and successful resuscitation. critically ill patients have low selenium blood levels. Therefore the investigators hypothesize that giving selenium after cardiac arrest and successful resuscitation might improve brain function.

Study Overview

• Status: Withdrawn
• Conditions: Cardiac Arrest
• Intervention / Treatment: Drug: Sodium-selenite; Drug: Placebo

Detailed Description

When cardiopulmonary resuscitation results in the return of spontaneous circulation, intensive care is required to optimize neurological recovery. The pathophysiological reactions that follow hypoxic brain injury are complex, and the mechanisms by which ischemia causes neuronal death leading to postanoxic encephalopathy are only partly understood to date. Therapeutic hypothermia improves brain function after cardiopulmonary resuscitation. Injury however can be ongoing even after the return of spontaneous circulation, giving the clinician an additional window of opportunity to treat and protect the injured brain [5]. Therefore there is an unmet clinical need for further therapeutic strategies. Strategies to counteract the deleterious effects of oxygen-derived free radicals after cerebral reperfusion have been studied for long.

The trace element selenium is part of the enzyme glutathione peroxidase which belongs to the endogenous defence mechanisms against oxidative stress. Clinical data suggest that supplementation of selenium may be beneficial in critically ill patients and in neurodegenerative diseases including, among others, Parkinson's disease, stroke, and epilepsy, where oxidative stress plays an important pathophysiological role. In SIRS, sepsis and septic shock doses up to 4000µg per day have been proven to be safe A recent retrospective analysis supported the hypothesis that early administration of selenium may improve neurological outcome after cardiac arrest.

Therefore the purpose of this study is to explore the influence of early administration of selenium on neurological outcome after cardiopulmonary resuscitation by a randomized, placebo-controlled, single-center study.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8010
    • Department of Internal Medicine, Medical University of Graz

Participation Criteria

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:

• Cardiac arrest
• Successful Resuscitation
• Age >18

Exclusion Criteria:

• Polytrauma
• Pregnancy
• Any condition that makes it likely that the patient will not survive 24 hours

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sodium-selenite infusion; Di-sodium-selenite-pentahydrate (Na 2SeO3.5H2O) in 0,9% sodium chloride is administered intravenously at a does of 3000µg on day 0, 2000µg on day 1 and 2 and at a dose of 1000µg per day on day 3-6.	Drug: Sodium-selenite; Di-sodium-selenite-pentahydrate (Na 2SeO3.5H2O) in 0,9% sodium chloride is administered intravenously at a does of 3000µg on day 0, 2000µg on day 1 and 2 and at a dose of 1000µg per day on day 3-6.; Other Names: selenase
Placebo Comparator: Placebo; 0.9% sodium chloride	Drug: Placebo; 0,9% sodium chloride is administered intravenously; Other Names: 0,9% sodium chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
neuron specific enolase	Reduction of neuron specific enolase below by more than 4.4 µg/l at 72 hours after admission to the hospital	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
inflammation	Reduction of C-reactive protein, procalcitonin, interleukin 6	7 days
oxidative stress markers	Reduction in peroxide, peroxidase, OLAB, MDA-LDL IG, TAC, ADMA, selenium and glutathione peroxidase levels	7 days
neurological function	Improvement of NIH stroke scale and Glasgow Pittsburgh Performance score	6 months
Selenium blood levels	Increase in selenium levels in whole blood	7 days
glutathion peroxidase plasma levels	Improvement in glutathion peroxidase plasma levels	7 days

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Investigators: Principal Investigator: Vanessa Stadlbauer, MD, Department of Internal Medicine, Medical University of Graz

Study record dates

Study Major Dates

• Study Start: January 1, 2017
• Primary Completion (Anticipated): July 1, 2018
• Study Completion (Anticipated): July 1, 2019

Study Registration Dates

• First Submitted: July 4, 2011
• First Submitted That Met QC Criteria: July 7, 2011
• First Posted (Estimate): July 11, 2011

Study Record Updates

• Last Update Posted (Actual): December 13, 2017
• Last Update Submitted That Met QC Criteria: December 12, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: cardiac arrest; resuscitation; neurological outcome
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Arrest; Physiological Effects of Drugs; Trace Elements; Micronutrients; Selenious Acid; Sodium Selenite
• Other Study ID Numbers: SCRP2011; 2011-001074-26 (EudraCT Number)