Clinical trial NCT02002247: SodiUm SeleniTe Adminstration IN Cardiac Surgery (SUSTAIN CSX®-Trial).
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Heart Disease
Keywords: antioxidants
selenium
heart disease
cardiac surgery
perioperative
Lead sponsor: Clinical Evaluation Research Unit at Kingston General Hospital
Sponsor class: OTHER
Collaborators: name: biosyn Arzneimittel GmbH
name: Queen's University
name: RWTH Aachen University
First posted: 2013-12-05
Enrollment: 1400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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).

Primary outcomes:
measure: PODS free days + alive
timeFrame: 30 Day
Secondary outcomes:
measure: 30-Day Mortality
timeFrame: 30 Day
measure: Hospital Acquired Infections
timeFrame: 30 day
measure: Perioperative hemodynamic profile
timeFrame: 6 months
measure: Cardiovascular Complications
timeFrame: 6-months
measure: Duration of Mechanical Ventilation
timeFrame: 6-months
measure: Incidence of post-operative delirium
timeFrame: 6-months
measure: ICU Length of stay
timeFrame: 6-months
measure: Hospital Re-admission Rates
timeFrame: 6-months
measure: Hospital Length of stay
timeFrame: 6-months
measure: 6-Month Survival
timeFrame: 6-months
measure: Quality of Life
timeFrame: 6-months
measure: Return to work
timeFrame: 6-months
measure: 6-minute walking test
timeFrame: up to 3 months
Other outcomes:
measure: Laboratory outcomes
timeFrame: POD 10
Locations:
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Institut de cardiologie de Montreal
state: Quebec
city: Montreal
country: Canada
facility: Sir Mortimer B. Davis Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Montreal
country: Canada
facility: Sacre Coeur
state: Quebec
city: Quebec City
country: Canada
facility: IUCPQ
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre de recherche CIUSSS de l'Estrie CHUS
state: Quebec
city: Aachen
country: Germany
facility: RWTH Aachen University Hospital
city: Bonn
country: Germany
facility: Klinik und Poliklinik für Anästhesiologie und Operative Intensivmedizin Universitätsklinikum Bonn
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Freiburg
country: Germany
facility: Klinik für Her- und Gefäßchirurgie Universitäts-Herzzentrum Freiburg
city: Gießen
country: Germany
facility: Klinik für Herz-, Kinderherz- und Gefäßchirurgie UKGM Giessen
city: Kiel
country: Germany
facility: University Medical Center Schleswig-Holstein
city: Koln
country: Germany
facility: Klinik und Poliklinik für Herz- und Thoraxchirurgie Uniklinik Köln
city: Mainz
country: Germany
facility: Klinik für Anästhesiologie Universitätsmedizin Mainz
city: München
country: Germany
facility: Klinik für Anästhesiologie Klinikum der Universität München
city: Münster
country: Germany
facility: Klinik für Anästhesiologie, operative Intensivmedizin und Schmerztherapie Universitätsmedizin Münster, Zentralklinikum
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg gGmbH Universitätsklinik für Anästhesiologie / Intensivmedizin / Notfallmedizin / Schmerztherapie
Study officials:
affiliation: Queen's University
name: Daren K Heyland, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: RWTH Aachen University Hospital
name: Christian Stoppe, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ottawa Heart Institute Research Corporation
name: Bernard J McDonald, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stoppe C, McDonald B, Rex S, Manzanares W, Whitlock R, Fremes S, Fowler R, Lamarche Y, Meybohm P, Haberthur 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.