High-dose Selenium Supplementation in Patients With Left Ventricular Assist

Study Overview
=================
Brief Summary
-----------------
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.

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

Conditions
-----------------
Ventricular Dysfunction, Left

Intervention / Treatment
-----------------
* Drug: Selenium Supplement (sodium selenite)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Selenium Supplement (sodium selenite)<br>Active arm receiving Selenium in form of sodium selenite | Drug: Selenium Supplement (sodium selenite)<br>* 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).<br>* Other names: Selenase (R) T;|
| Placebo Comparator: Placebo<br>Placebo arm receiving Sodium Chloride solution | Drug: Placebo<br>* 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).<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Heart Failure, Cardiac Surgery, Ventricular Assist Device, Selenium