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

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ClinicalTrials.gov Identifier: NCT02002247
Recruitment Status : Recruiting
First Posted : December 5, 2013
Last Update Posted : January 27, 2020
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

Tracking Information
First Submitted Date  ICMJE November 28, 2013
First Posted Date  ICMJE December 5, 2013
Last Update Posted Date January 27, 2020
Study Start Date  ICMJE January 2015
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 13, 2017)
PODS free days + alive [ Time Frame: 30 Day ]
Evaluate the PODS free days + alive 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).
Original Primary Outcome Measures  ICMJE
 (submitted: November 29, 2013)
  • Feasibility [ Time Frame: 6-month ]
    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 ]
    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).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 24, 2020)
  • 30-Day Mortality [ Time Frame: 30 Day ]
    Mortality 30 days post-randomization.
  • Hospital Acquired Infections [ Time Frame: 30 day ]
    To be evaluated up to 6 months post-randomization.
  • Perioperative hemodynamic profile [ Time Frame: 6 months ]
    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 ]
    This includes: arrhythmias, cardiac arrest, infarction. To be assessed up to 6-months.
  • Duration of Mechanical Ventilation [ Time Frame: 6-months ]
    To be assessed up to 6-months.
  • Incidence of post-operative delirium [ Time Frame: 6-months ]
    Assessed by CAM-ICU score. To be assessed up to 6-months.
  • ICU Length of stay [ Time Frame: 6-months ]
    To be assessed up to 6 months post-randomization.
  • Hospital Re-admission Rates [ Time Frame: 6-months ]
    To be assessed up to 6-months post-randomization.
  • Hospital Length of stay [ Time Frame: 6-months ]
    To be assessed up to 6 months post-randomization.
  • 6-Month Survival [ Time Frame: 6-months ]
    To be assessed at 6 months post-randomization.
  • Quality of Life [ Time Frame: 6-months ]
    Health related quality of life to be assessed up to 6-months post-randomization.
  • Return to work [ Time Frame: 6-months ]
    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.
  • 6-minute walking test [ Time Frame: up to 3 months ]
    6-minute walking distance
Original Secondary Outcome Measures  ICMJE
 (submitted: November 29, 2013)
  • 30-Day Mortality [ Time Frame: 30 Day ]
    Mortality 30 days post-randomization.
  • Hospital Acquired Infections [ Time Frame: 30 day ]
    To be evaluated up to 6 months post-randomization.
  • Perioperative hemodynamic profile [ Time Frame: 6 months ]
    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 ]
    This includes: arrhythmias, cardiac arrest, infarction. To be assessed up to 6-months.
  • Duration of Mechanical Ventilation [ Time Frame: 6-months ]
    To be assessed up to 6-months.
  • Incidence of post-operative delerium [ Time Frame: 6-months ]
    Assessed by CAM-ICU score. To be assessed up to 6-months.
  • ICU Length of stay [ Time Frame: 6-months ]
    To be assessed up to 6 months post-randomization.
  • Hospital Re-admission Rates [ Time Frame: 6-months ]
    To be assessed up to 6-months post-randomization.
Current Other Pre-specified Outcome Measures
 (submitted: May 18, 2016)
Laboratory outcomes [ Time Frame: POD 10 ]
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.
Original Other Pre-specified Outcome Measures
 (submitted: November 29, 2013)
Laboratory outcomes [ Time Frame: POD 10 ]
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.
 
Descriptive Information
Brief Title  ICMJE SodiUm SeleniTe Adminstration IN Cardiac Surgery (SUSTAIN CSX®-Trial).
Official Title  ICMJE SodiUm SeleniTe Adminstration IN Cardiac Surgery (SUSTAIN CSX®-Trial). A Multicentre Randomized Controlled Trial of High Dose Sodium-selenite Administration in High Risk Cardiac Surgical Patients
Brief Summary 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.
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 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Heart Disease
Intervention  ICMJE
  • 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%
Study Arms  ICMJE
  • 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
Publications * 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.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 18, 2016)
1400
Original Estimated Enrollment  ICMJE
 (submitted: November 29, 2013)
180
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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; OR
    • 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:

  • Isolated procedures (CABG only or valve)
  • 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.
  • Alternate contacts of investigators (required by German Regulatory Authorities).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Daren K Heyland, MD 613-549-6666 ext 4847 dkh2@queensu.ca
Listed Location Countries  ICMJE Canada,   Germany
Removed Location Countries Belgium,   Switzerland,   United States
 
Administrative Information
NCT Number  ICMJE NCT02002247
Other Study ID Numbers  ICMJE SUSTAIN CSX
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Daren K. Heyland, Clinical Evaluation Research Unit at Kingston General Hospital
Study Sponsor  ICMJE Daren K. Heyland
Collaborators  ICMJE
  • biosyn Arzneimittel GmbH
  • Queen's University
  • RWTH Aachen University
Investigators  ICMJE
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
PRS Account Clinical Evaluation Research Unit at Kingston General Hospital
Verification Date January 2020

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