SodiUm SeleniTe Adminstration IN Cardiac Surgery (SUSTAIN CSX®-Trial). (SUSTAINCSX)
Drug: sodium selenite
Drug: Placebo (for sodium-selenite)
|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|
- 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).
- 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. 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.
|Study Start Date:||January 2015|
|Estimated Study Completion Date:||September 2016|
|Estimated Primary Completion Date:||September 2016 (Final data collection date for primary outcome measure)|
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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02002247
|Contact: Daren K Heyland, MD||613-549-6666 ext email@example.com|
|Contact: Christian Stoppe, MDfirstname.lastname@example.org|
|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|
|Institut de cardiologie de Montreal||Recruiting|
|Montreal, Quebec, Canada, H1C1T8|
|Contact: Yoan Lamarche, MD|
|Principal Investigator: Yoan Lamarche, MD|
|RWTH Aachen University Hospital||Recruiting|
|Aachen, Germany, 52074|
|Contact: Christian Stoppe, MD 0049-024108036575 email@example.com|
|Principal Investigator: Christian Stoppe, MD|
|Universitätsklinikum Frankfurt||Not yet recruiting|
|Frankfurt, Germany, 60590|
|Contact: Patrick Meybohm, MD : 069/ 6301 - 5998 firstname.lastname@example.org|
|Principal Investigator: Patrick Meybohm, MD|
|University Medical Center Schleswig-Holstein||Not yet recruiting|
|Contact: Gunnar Elke, MD +49 431 5972991 email@example.com|
|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|