High-dose Selenium Supplementation in Patients With Left Ventricular Assist (SOS-LVAD)

Perioperative High-dose Selenium Supplementation in Patients With Left Ventricular Assist Device - a Double Blinded Randomised Controlled Trial

This planned pilot study is a monocentric, prospective, double-blind randomized and placebo controlled clinical study. The SOS-LVAD Trial can be assigned to the clinical Phase III.

The aim of the present trial is to provide the scientific rationale for a large multicenter clinical trial, investigating the effects of perioperative high dose selenium supplementation in high-risk cardiac surgical patients undergoing complicated open heart surgery with prolonged time on cardiopulmonary bypass (CPB) and LVAD Implant. The investigators hypothesize that the therapeutic strategy tested in this randomized trial may contribute to a faster independency from life-sustaining technologies in the ICU and a decrease of postoperative morbidity and mortality. Before proceeding to the large-scale, definitive trial, the investigators propose to conduct a pilot study of the definitive randomized trial, to determine the feasibility of the study protocol.

Study Overview

• Status: Completed
• Conditions: Ventricular Dysfunction, Left
• Intervention / Treatment: Drug: Selenium Supplement (sodium selenite); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • NRW
    • Aachen, NRW, Germany, 52074
      • Dep. of Thoracic and Cardiovascular Surgery, University Hospital RWTH Aachen

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:

• Patients with chronic left ventricular heart failure, who undergo LVAD Implant surgery (including other heart surgery)
• Full aged, contractually capable, male and female patients
• Patients that are capable and willing to understand and obey the instructions of the study staff.
• Signed informed consent

Exclusion criteria:

• Selenium intoxication
• Patients with contraindications to the planned intervention, due to diseases
• Severe exacerbation of comorbidities such as renal failure requiring dialysis or liver dysfunction (defined as bilirubin >2mg/dl)
• Known hypersensitivity to the trial medication (selenase® 300 RP, selenase® T), to any of the constituents of the solution or to the placebo
• Patients that are not contractually capable; Patients accommodated to a facility by court order or public authority
• Pregnancy or lactation period
• Women at reproductive age, without suitable contraception
• Patients in a relationship of dependency or in employment with the head of study's
• Underaged
• No signed informed consent
• Simultaneous participation in another clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Selenium Supplement (sodium selenite); Active arm receiving Selenium in form of sodium selenite	Drug: Selenium Supplement (sodium selenite); On the evening before operation the patient receives the first dosage of Selenium (300µg orally) orally as a pill. After induction of anaesthesia and before being put on the heart-lung-machine the patient receives 3000µg Selenium as sodium selenite (selenase® T) intravenous (as bolus infusion in the space of 30 minutes). In addition the patient gets 1000µg Selenium as sodium selenite (selenase® T) intravenous as bolus infusion in the space of 30 minutes after admission to ICU. On every POD the patient receives 1000µg Selenium as sodium selenite (selenase® T) intravenous as bolus infusion in the space of 30 minutes (until transfer to standard care unit or maximum substitution until 13th POD).; Other Names: Selenase (R) 300 RP; Selenase (R) T
Placebo Comparator: Placebo; Placebo arm receiving Sodium Chloride solution	Drug: Placebo; On the evening before operation the patient receives the first dosage of placebo orally as a pill. After induction of anaesthesia and before being put on the heart-lung-machine the patient receives placebo intravenous (as bolus infusion in the space of 30 minutes). In addition the patient gets placebo intravenous as bolus infusion in the space of 30 minutes after admission to ICU. On every POD the patient receives placebo intravenous as bolus infusion in the space of 30 minutes (until transfer to standard care unit or maximum substitution until 13th POD).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Outcome: independence from specific ICU procedures	As primary outcome, the investigators have chosen a composite outcome. This allows to assess the postoperative process of the included patients irrespective of extrinsic sources of irritation (e.g. daily routine, clinic based processes). The independency from specific ICU procedures is taken as a primary target (time is taken from postoperative admission to ICU after implantation of LVAD until the end of the characteristic ICU procedures): mechanical ventilation; vasopressor therapy; mechanical circulatory support; renal replacement therapy	postoperative day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	via telephone enquiry	postoperative day 28
Persistent organ dysfunction	Persistent organ dysfunction quantified upon day 7 (or upon day of discharge from hospital) with "Sequential Organ Failure Assessment Score" (SOFA), "Multiple Organ Dysfunction Score" (MODS) and "Simplified Acute Physiology Score" (SAPS), daily quantification while ICU stay	postoperative day 7
Incidence of nosocomial infections acquired at ICU		participants will be followed for the duration of hospital stay, an expected average of 5-10 days
Acute renal failure	(quantified with RIFLE score)	participants will be followed for the duration of hospital stay, an expected average of 5-10 days
Mechanical Ventilation	Time of mechanical ventilation (measured in hours after successful intubation) and necessity of re-intubation	participants will be followed for the duration of hospital stay, an expected average of 5-10 days
postoperative delirium	Evaluation of delirium by confusion assessment method: CAM-ICU score	participants will be followed for the duration of hospital stay, an expected average of 5-10 days
Selenium concentration in whole blood, activity of glutathion-peroxidase, concentration of Selenoprotein-P (Sel-P)		preoperative, by the end of surgery, on day 1, 3, 5, 7, 13, and if the patient is still in hospital, on day 28.
Quality of Life	The patients individual "Quality of Life" (pre- and postoperative) quantified with "MACNEW - Health related quality of life in heart disease - Scale" quantified postoperative upon discharge from hospital and on the 28th POD via telephone inquiry. If the patient cannot be contacted via telephone on the 28th POD, we will try to reach the patient on the following 7 days.	postoperative day 28

Collaborators and Investigators

• Sponsor: RWTH Aachen University
• Collaborators: biosyn Arzneimittel GmbH; Cardiodevice Stiftung
• Investigators: Principal Investigator: Andreas Goetzenich, MD, PhD, Dep. of Thoracic and Cardiovascular Surgery, University Hospital RWTH Aachen; Principal Investigator: Christian Stoppe, MD, Dep. of Thoracic and Cardiovascular Surgery, University Hospital RWTH Aachen

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: August 17, 2015
• First Submitted That Met QC Criteria: August 19, 2015
• First Posted (Estimate): August 21, 2015

Study Record Updates

• Last Update Posted (Actual): February 7, 2018
• Last Update Submitted That Met QC Criteria: February 6, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Heart Failure; Cardiac Surgery; Selenium; Ventricular Assist Device
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Ventricular Dysfunction; Ventricular Dysfunction, Left; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Trace Elements; Micronutrients; Antioxidants; Selenious Acid; Sodium Selenite; Selenium
• Other Study ID Numbers: 13-036