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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Heart Disease	Drug: sodium selenite; Drug: Placebo	Phase 3

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 Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	1400 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	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
Study Start Date :	January 2015
Estimated Primary Completion Date :	December 2019
Estimated Study Completion Date :	June 2020

Arms and Interventions

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Arm	Intervention/treatment
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; 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%
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 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

Outcome Measures

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Primary Outcome Measures :

1. 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).

Secondary Outcome Measures :

1. 30-Day Mortality [ Time Frame: 30 Day ]
   Mortality 30 days post-randomization.
2. Hospital Acquired Infections [ Time Frame: 30 day ]
   To be evaluated up to 6 months post-randomization.
3. 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.
4. Cardiovascular Complications [ Time Frame: 6-months ]
   This includes: arrhythmias, cardiac arrest, infarction. To be assessed up to 6-months.
5. Duration of Mechanical Ventilation [ Time Frame: 6-months ]
   To be assessed up to 6-months.
6. Incidence of post-operative delirium [ Time Frame: 6-months ]
   Assessed by CAM-ICU score. To be assessed up to 6-months.
7. ICU Length of stay [ Time Frame: 6-months ]
   To be assessed up to 6 months post-randomization.
8. Hospital Re-admission Rates [ Time Frame: 6-months ]
   To be assessed up to 6-months post-randomization.
9. Hospital Length of stay [ Time Frame: 6-months ]
   To be assessed up to 6 months post-randomization.
10. 6-Month Survival [ Time Frame: 6-months ]
    To be assessed at 6 months post-randomization.
11. Quality of Life [ Time Frame: 6-months ]
    Health related quality of life to be assessed up to 6-months post-randomization.
12. 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.

Other Outcome Measures:

1. 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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
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; 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).

Contacts and Locations

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Contacts

Contact: Daren K Heyland, MD	613-549-6666 ext 4847	dkh2@queensu.ca

Locations

Canada, Ontario
Hamilton General Hospital	Recruiting
Hamilton, Ontario, Canada
Contact: Whitlock Richard, MD
London Health Sciences Centre	Recruiting
London, Ontario, Canada
Contact: Phil Jones, MD
University of Ottawa Heart Institute	Recruiting
Ottawa, Ontario, Canada
Contact: Bernard J McDonald, MD
Principal Investigator: Bernard J McDonald, MD
Sunnybrook Health Sciences Centre	Recruiting
Toronto, Ontario, Canada, M4N3M5
Principal Investigator: Stephen Fremes, MD
Principal Investigator: Robert Fowler, MD
St. Michael's Hospital	Recruiting
Toronto, Ontario, Canada
Contact: David Mazer, MD
Toronto General Hospital	Recruiting
Toronto, Ontario, Canada
Contact: Matteo Parotto, MD
Canada, Quebec
Institut de cardiologie de Montreal	Recruiting
Montreal, Quebec, Canada, H1C1T8
Contact: Yoan Lamarche, MD
Principal Investigator: Yoan Lamarche, MD
Sir Mortimer B. Davis Jewish General Hospital	Recruiting
Montreal, Quebec, Canada, H3T 1E2
Contact: Matthew Cameron, MD
McGill University Health Centre	Recruiting
Montreal, Quebec, Canada
Contact: Roupen Hatzakorzian, MD
Sacre Coeur	Recruiting
Montreal, Quebec, Canada
Contact: Yoan Lamarche, MD
IUCPQ	Recruiting
Quebec City, Quebec, Canada
Contact: Siamak Mohammadi, MD
Germany
RWTH Aachen University Hospital	Recruiting
Aachen, Germany, 52074
Contact: Christian Stoppe, MD 0049-024108036575 cstoppe@ukaachen.de
Principal Investigator: Christian Stoppe, MD
Klinik und Poliklinik für Anästhesiologie und Operative Intensivmedizin Universitätsklinikum Bonn	Recruiting
Bonn, Germany
Contact: Maria Wittman, MD
Universitätsklinikum Frankfurt	Recruiting
Frankfurt, Germany, 60590
Contact: Patrick Meybohm, MD : 069/ 6301 - 5998 patrick.meybohm@kgu.de
Principal Investigator: Patrick Meybohm, MD
Klinik für Her- und Gefäßchirurgie Universitäts-Herzzentrum Freiburg	Recruiting
Freiburg, Germany
Contact: Georg Trummer, MD
Klinik für Herz-, Kinderherz- und Gefäßchirurgie UKGM Giessen	Recruiting
Gießen, Germany
Contact: Bernd Niemann, MD
University Medical Center Schleswig-Holstein	Recruiting
Kiel, Germany
Contact: Gunnar Elke, MD +49 431 5972991 gunnar.elke@uksh.de
Klinik und Poliklinik für Herz- und Thoraxchirurgie Uniklinik Köln	Recruiting
Koln, Germany
Contact: Oliver Liakopoulos, MD
Klinik für Anästhesiologie Universitätsmedizin Mainz	Recruiting
Mainz, Germany
Contact: Rita Laufenberg, MD
Klinik für Anästhesiologie Klinikum der Universität München	Recruiting
München, Germany
Contact: Erich Kilger, MD
Klinik für Anästhesiologie, operative Intensivmedizin und Schmerztherapie Universitätsmedizin Münster, Zentralklinikum	Recruiting
Münster, Germany
Contact: Thomas Ermert, MD
Klinikum Oldenburg gGmbH Universitätsklinik für Anästhesiologie / Intensivmedizin / Notfallmedizin / Schmerztherapie	Recruiting
Oldenburg, Germany
Contact: Malte Book, MD
Contact: Thomas Grote, MD
Klinik und Poliklinik für Anästhesiologie und Intensivtherapie Universitätsmedizin Rostock	Not yet recruiting
Rostock, Germany
Contact: Frank Kletzin

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	Ottawa Heart Institute Research Corporation

More Information

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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
First Posted:	December 5, 2013
Last Update Posted:	September 28, 2018
Last Verified:	September 2018

Keywords provided by Daren K. Heyland, Clinical Evaluation Research Unit at Kingston General Hospital:

antioxidants; selenium; heart disease; cardiac surgery; perioperative

Additional relevant MeSH terms:

Heart Diseases; Sodium Selenite; Cardiovascular Diseases; Selenium; Selenious Acid; Antioxidants	Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Trace Elements; Micronutrients; Growth Substances