Heart Disease
Conditions
Keywords
antioxidants, selenium, heart disease, cardiac surgery, perioperative
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.
Interventions
DRUGsodium 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.
DRUGPlacebo
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.
Sponsors
biosyn Arzneimittel GmbH
Queen's University
RWTH Aachen University
Daren K. Heyland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PODS free days + alive | 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
| Measure | Time frame | Description |
|---|---|---|
| Hospital Acquired Infections | 30 day | To be evaluated up to 6 months post-randomization. |
| Perioperative hemodynamic profile | 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 | 6-months | This includes: arrhythmias, cardiac arrest, infarction. To be assessed up to 6-months. |
| Duration of Mechanical Ventilation | 6-months | To be assessed up to 6-months. |
| Incidence of post-operative delirium | 6-months | Assessed by CAM-ICU score. To be assessed up to 6-months. |
| ICU Length of stay | 6-months | To be assessed up to 6 months post-randomization. |
| Hospital Re-admission Rates | 6-months | To be assessed up to 6-months post-randomization. |
| Hospital Length of stay | 6-months | To be assessed up to 6 months post-randomization. |
| 6-Month Survival | 6-months | To be assessed at 6 months post-randomization. |
| Quality of Life | 6-months | Health related quality of life to be assessed up to 6-months post-randomization. |
| Return to work | 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 | up to 3 months | 6-minute walking distance |
| 30-Day Mortality | 30 Day | Mortality 30 days post-randomization. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Laboratory outcomes | 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. |
Countries
Canada, Germany
Outcome results
None listed