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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2016 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: May 18, 2016
Last verified: May 2016

November 28, 2013
May 18, 2016
January 2015
December 2019   (final data collection date for primary outcome measure)
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).
  • 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).
Complete list of historical versions of study NCT02002247 on ClinicalTrials.gov Archive Site
  • 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 delirium [ 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.
  • Hospital Length of stay [ Time Frame: 6-months ] [ Designated as safety issue: Yes ]
    To be assessed up to 6 months post-randomization.
  • 6-Month Survival [ Time Frame: 6-months ] [ Designated as safety issue: Yes ]
    To be assessed at 6 months post-randomization.
  • Quality of Life [ Time Frame: 6-months ] [ Designated as safety issue: Yes ]
    Health related quality of life to be assessed up to 6-months post-randomization.
  • Return to work [ Time Frame: 6-months ] [ Designated as safety issue: Yes ]
    Assessed using a questionnaire to determine the patient's ability to return to their pre-operative working capabilities. To be assessed up to 6 months post-randomization.
  • 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.
Laboratory outcomes [ Time Frame: POD 10 ] [ Designated as safety issue: Yes ]

To be assessed up to post-operative day (POD) 10 in patients who consent to this optional blood work.

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.

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.
 
SodiUm SeleniTe Adminstration IN Cardiac Surgery (SUSTAIN CSX®-Trial).
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
The aim of the investigators' research program is to investigate the effects of perioperative high dose selenium supplementation in high-risk cardiac surgical patients undergoing complicated open heart surgery. The investigators hypothesize that the therapeutic strategy tested in this randomized trial may contribute to a fewer complications, less organ injury and fewer deaths. Before the investigators conducted the large definitive trial, they conducted a pilot study to assess the feasibility of the protocol, and are rolling the pilot patients into the definitive trial.

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 the 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 this program of research is to conduct a randomized trial.

The aim of this research program is to investigate the effects of perioperative high dose selenium supplementation in high-risk cardiac surgical patients undergoing complicated open heart surgery. The investigators hypothesize that the therapeutic strategy tested in this randomized trial may contribute to fewer complications, less organ injury and fewer deaths.

The investigators propose to conduct a randomized, placebo-controlled, double-blind, multicentre definitive trial of 1400 patients across 20 sites in Germany and Canada, which will include the pilot study patients. An industry partner (Biosyn) will provide the product and some additional 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 the hypothesis is proven true, and this simple, inexpensive nutrient reduces complications and improves recovery of patients undergoing cardiac surgery, there is the potential to dramatically change clinical practice and improve health outcomes.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Heart Disease
  • 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 an IV bolus 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
  • Drug: Placebo
    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 an IV bolus 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%
  • 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.
    Intervention: Drug: Placebo
  • 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.

    Intervention: Drug: sodium selenite
Stoppe C, McDonald B, Rex S, Manzanares W, Whitlock R, Fremes S, Fowler R, Lamarche Y, Meybohm P, Haberthür C, Rossaint R, Goetzenich A, Elke G, Day A, Heyland DK. SodiUm SeleniTe Adminstration IN Cardiac Surgery (SUSTAIN CSX-trial): study design of an international multicenter randomized double-blinded controlled trial of high dose sodium-selenite administration in high-risk cardiac surgical patients. Trials. 2014 Aug 28;15:339. doi: 10.1186/1745-6215-15-339.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
1400
June 2020
December 2019   (final data collection date for primary outcome measure)

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.
  • Renal failure requiring dialysis at the point of screening.
  • 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.
  • Family members of investigators (required by German Regulatory Authorities).
Both
18 Years and older   (Adult, Senior)
No
Contact: Daren K Heyland, MD 613-549-6666 ext 4847 dkh2@queensu.ca
Contact: Christian Stoppe, MD 00492418036575 christian.stoppe@gmail.com
Canada,   Germany
Belgium,   Switzerland,   United States
 
NCT02002247
SUSTAIN CSX
Yes
Not Provided
Not Provided
Daren K. Heyland, Clinical Evaluation Research Unit at Kingston General Hospital
Daren K. Heyland
  • biosyn Arzneimittel GmbH
  • Queen's University
  • RWTH Aachen University
Principal Investigator: Daren K Heyland, MD Queen's University
Principal Investigator: Christian Stoppe, MD RWTH Aachen University Hospital
Principal Investigator: Bernard J McDonald, MD Ottawa Heart Institute Research Corporation
Clinical Evaluation Research Unit at Kingston General Hospital
May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP