SodiUm SeleniTe Adminstration IN Cardiac Surgery (SUSTAIN CSX®-Trial). (SUSTAINCSX)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2014 by Clinical Evaluation Research Unit at Kingston General Hospital
Sponsor:
Collaborators:
biosyn Arzneimittel GmbH
Queen's University
RWTH Aachen University
Information provided by (Responsible Party):
Daren K. Heyland, Clinical Evaluation Research Unit at Kingston General Hospital
ClinicalTrials.gov Identifier:
NCT02002247
First received: November 28, 2013
Last updated: April 25, 2014
Last verified: April 2014
  Purpose

The aim of our research program is to investigate the effects of perioperative high dose selenium supplementation in high-risk cardiac surgical patients undergoing complicated open heart surgery. We hypothesize that the therapeutic strategy tested in this randomized trial may contribute to a fewer complications, less organ injury and fewer deaths. Before we conduct a very large, international trial testing this hypothesis, we must first conduct a pilot study to assess the feasibility of this protocol.


Condition Intervention Phase
Heart Disease
Drug: sodium selenite
Drug: Placebo (for sodium-selenite)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: SodiUm SeleniTe Adminstration IN Cardiac Surgery (SUSTAIN CSX®-Trial). A Pilot Randomized Controlled Trial of High Dose Sodium-selenite Administration in High Risk Cardiac Surgical Patients

Resource links provided by NLM:


Further study details as provided by Clinical Evaluation Research Unit at Kingston General Hospital:

Primary Outcome Measures:
  • Feasibility [ Time Frame: 6-month ] [ Designated as safety issue: No ]
    Feasibility of this study will be measured by: 1) Recruitment of trial patients; 2) Adherence to protocol; and 3) Contamination.

  • PODS + death [ Time Frame: 6-month ] [ Designated as safety issue: Yes ]
    Evaluate the use of PODS+death as the primary outcome for the large-scale Phase III trial. We define PODS as the need for life-sustaining therapies (mechanical ventilation, vasopressor therapy, mechanical circulatory support, continuous renal replacement therapy, or intermittent hemodialysis).


Secondary Outcome Measures:
  • 30-Day Mortality [ Time Frame: 30 Day ] [ Designated as safety issue: Yes ]
    Mortality 30 days post-randomization.

  • Hospital Acquired Infections [ Time Frame: 30 day ] [ Designated as safety issue: Yes ]
    To be evaluated up to 6 months post-randomization.

  • Perioperative hemodynamic profile [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    This includes: mean arterial blood pressure, cardiac power index, systemic vascular resistance, etc... To be assessed up to 6-months post-randomization.

  • Cardiovascular Complications [ Time Frame: 6-months ] [ Designated as safety issue: Yes ]
    This includes: arrhythmias, cardiac arrest, infarction. To be assessed up to 6-months.

  • Duration of Mechanical Ventilation [ Time Frame: 6-months ] [ Designated as safety issue: Yes ]
    To be assessed up to 6-months.

  • Incidence of post-operative delerium [ Time Frame: 6-months ] [ Designated as safety issue: Yes ]
    Assessed by CAM-ICU score. To be assessed up to 6-months.

  • ICU Length of stay [ Time Frame: 6-months ] [ Designated as safety issue: Yes ]
    To be assessed up to 6 months post-randomization.

  • Hospital Re-admission Rates [ Time Frame: 6-months ] [ Designated as safety issue: Yes ]
    To be assessed up to 6-months post-randomization.


Other Outcome Measures:
  • Laboratory outcomes [ Time Frame: POD 10 ] [ Designated as safety issue: Yes ]
    To be assessed up to post-operative day (POD) 10. To assess the potential effects of supplementation on selenium levels, safety parameters and other mechanistic markers. Whole blood levels of selenium, selenoprotein P (Sel-P), antibodies against oxidized LDL, markers of inflammation (interleukin[IL]-6, IL-10, TNF alpha) and activity of glutathione-peroxidase (GPx) will be assessed to determine the efficacy of selenium supplementation in these patients.


Estimated Enrollment: 80
Study Start Date: September 2014
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Normal saline will be administered to subjects intravenously pre-operatively, upon admission to the ICU, then daily up to post-operative day 10 or ICU discharge, whichever occurs first.
Drug: Placebo (for sodium-selenite)
All patients will receive an IV bolus of normal saline (equals to 40ml prepared solution) within 30min after induction of anesthesia via the central venous catheter. After termination of surgery, immediately after admission to the ICU, all patients will receive a second bolus of normal saline accordingly. Then on every further morning during ICU-stay, patients will receive a continuous infusion of normal saline via central or peripheral venous access until death, discharge from ICU to the ward (treatment may continue in a step down or intermediate care unit), or for a maximum of 10 days.
Other Name: NaCl 0.9%
Active Comparator: sodium-selenite

High-dose sodium-selenite will be administered to subjects intravenously:

1) pre-operatively (2000 ug); 2) upon admission to the ICU (2000 ug), 3) then daily (1000 ug) up to post-operative day 10 or ICU discharge, whichever occurs first.

Drug: sodium selenite
All subjects will receive an IV bolus of 2000µg selenium within 30min after induction of anesthesia via the central venous catheter. After termination of surgery, immediately after admission to the ICU, all patients will receive a second bolus of 2000µg selenium. Then on every further morning during ICU-stay, patients will receive a continuous infusion of 1000µg selenium via central or peripheral venous access until death, discharge from ICU to the ward, or for a maximum of 10 days.
Other Name: selenium

Detailed Description:

Over a million patients undergo open heart surgery annually and this number is likely to accelerate as the population ages and the prevalence of diabetes and cardiovascular disease continue to increase. Unfortunately, death, organ failure, and other serious complications are all too frequent following open heart surgery, especially in some high-risk patient populations.

Selenium is a trace element that is important for many of the body's regulatory and metabolic functions especially during times of stress. International members of our study team have shown in a non-randomized study that high dose selenium supplementation was associated with improved clinical outcomes compared to a historical control group. The next step in our program of research is to conduct a randomized trial.

The aim of our research program is to investigate the effects of perioperative high dose selenium supplementation in high-risk cardiac surgical patients undergoing complicated open heart surgery. We hypothesize that the therapeutic strategy tested in this randomized trial may contribute to a fewer complications, less organ injury and fewer deaths. Before we conduct a very large, international trial testing this hypothesis, we must first conduct a pilot study to assess the feasibility of this protocol.

We propose to conduct a randomized, placebo-controlled, double-blind, multicentre pilot study of 80 patients in 6 sites located in Germany and Canada. We have an industry partner (Biosyn) that will provide us with product and support for the European sites. Patients will be randomized to receive either a daily perioperative high-dose selenium or placebo until postoperative day 10 (maximum) or upon earlier discharge from ICU. If our hypothesis is proven true, and this simple, inexpensive nutrient reduces complications and improves recovery of patients undergoing cardiac surgery, we have the potential to dramatically change clinical practice and improve health outcomes.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients (>18 years of age)
  • Scheduled to undergo elective or urgent cardiac surgery with the use of cardiopulmonary bypass (CPB) and cardioplegic arrest that exhibit a high perioperative risk profile as defined by the presence of one or more of the following:

    • a) Planned valve surgery combined with CABG or multiple valve replacement/repair surgeries or combined cardiac surgical procedures involving the thoracic aorta;
    • b) Any cardiac surgery with a high perioperative risk profile, defined as a predicted operative mortality of ≥ 5% (EuroSCORE II).

Exclusion Criteria:

We will exclude patients who meet any of the following criteria:

  • Known hypersensitivity to sodium-selenite or to any of the constituents of the solution.
  • Severe renal dysfunction as evidenced by pre-operative creatinine clearance <50 ml/min and/or severe pre-operative value of serum creatinine level above 200 micromoles/litre.
  • Chronic liver disease as evidenced by a pre-operative total bilirubin >2 mg/dl or 34 umol/L
  • Disabling neuropsychiatric disorders (severe dementia, severe Alzheimer's disease, advanced Parkinson's disease).
  • Pregnancy or lactation period.
  • Simultaneous participation in another clinical trial of an experimental therapy (co-enrolment acceptable in observational studies or randomized trials of existing therapies if permitted by both steering committees and local ethics boards).
  • Patients undergoing heart transplantation or preoperative planned LVAD insertion or complex congenital heart surgery.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02002247

Contacts
Contact: Daren K Heyland, MD 613-549-6666 ext 4847 dkh2@queensu.ca
Contact: Janet Overvelde 613-549-6666 ext 6241 overvelj@kgh.kari.net

Locations
Canada, Ontario
University of Ottawa Heart Institute Not yet recruiting
Ottawa, Ontario, Canada
Contact: Bernard J McDonald, MD         
Principal Investigator: Bernard J McDonald, MD         
Sunnybrook Health Sciences Centre Not yet recruiting
Toronto, Ontario, Canada, M4N3M5
Principal Investigator: Stephen Fremes, MD         
Principal Investigator: Robert Fowler, MD         
Canada, Quebec
Institut de cardiologie de Montreal Not yet recruiting
Montreal, Quebec, Canada, H1C1T8
Contact: Yoan Lamarche, MD         
Principal Investigator: Yoan Lamarche, MD         
Germany
RWTH Aachen University Hospital Not yet recruiting
Aachen, Germany, 52074
Contact: Christian Stoppe, MD    0049-024108036575    cstoppe@ukaachen.de   
Principal Investigator: Christian Stoppe, MD         
Universitätsklinikum Frankfurt Not yet recruiting
Frankfurt, Germany, 60590
Contact: Patrick Meybohm, MD    : 069/ 6301 - 5998    patrick.meybohm@kgu.de   
Principal Investigator: Patrick Meybohm, MD         
Sponsors and Collaborators
Daren K. Heyland
biosyn Arzneimittel GmbH
Queen's University
RWTH Aachen University
Investigators
Principal Investigator: Daren K Heyland, MD Queen's University
Principal Investigator: Christian Stoppe, MD RWTH Aachen University Hospital
Principal Investigator: Bernard J McDonald, MD University of Ottawa Heart Institute
  More Information

No publications provided

Responsible Party: Daren K. Heyland, Scientific Director, Clinical Evaluation Research Unit at Kingston General Hospital
ClinicalTrials.gov Identifier: NCT02002247     History of Changes
Other Study ID Numbers: SUSTAIN CSX
Study First Received: November 28, 2013
Last Updated: April 25, 2014
Health Authority: Canada: Health Canada
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Clinical Evaluation Research Unit at Kingston General Hospital:
antioxidants
selenium
heart disease
cardiac surgery
perioperative

Additional relevant MeSH terms:
Heart Diseases
Cardiovascular Diseases
Selenium
Sodium Selenite
Selenious Acid
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Trace Elements
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on September 18, 2014