About this trial
Open heart surgery, including coronary artery bypass grafting (CABG) and/or aortic valve replacement (AVR) is associated with a significant risk of mortality.
This study is a randomized clinical trial with the purpose of investigating four different interventions on the primary endpoint 'days alive and outside of hospital within 90 days'.
The interventions are:
* Dexamethasone vs. placebo administered after induction of anesthesia. * Olanzapine vs. placebo administered prior to anesthesia. * A blood-flow targeted vs. a blod-pressure targeted hemodynamic strategy while the patient is on cardio-pulmonary bypass (CPB) * Low-tidal volume ventilation vs. no ventilation of the lungs while the patient is on CPB
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Adult, i.e., above 18 years of age
Scheduled for CABG and/or AVR, irrespective of other concomitant valve surgery.
Disqualifiers
Acute surgery (i.e. off hours surgery)
Pregnancy or currently breastfeeding. Pregnancy in all fertile women will be ruled out by pregnancy testing prior to randomization.
Known endocarditis at time of screening
Previous participation in the trial
Trial design
Factorial
Treatments tested in this trial
Dexamethasone phosphate
DrugSee description of arms
Isotonic sodium chloride (0.9%)
DrugSee description of arms
Olanzapine 10 MG
DrugOlanzapine tablet pre-hidden in capsule identical to the placebo tablet
Placebo capsule
Drugcapsule identical to capsule containing olanzapine
Flow-targeted hemodynamic management
Procedure/SurgerySee description of arms
Pressure-targeted hemodynamic management
Procedure/SurgerySee description of arms
Low tidal-volume ventilation
Procedure/SurgerySee description of arms
No ventilation
Procedure/SurgerySee description of arms
Treatment groups
8
Treatment groupsSee each treatment group below.
Trial outcomes
Primary outcomes
Days alive and outside hospital
Secondary outcomes
Time to composite outcome of death and major organ damage
Time in days to occurrence of any component in a composite secondary endpoint during follow-up consisting of 1. Death from any cause 2. Stroke, defined as persisting (\>24 hours) of any neurological symptoms of neurological dysfunction during the 6 months follow-up period. The diagnosis is determined by the treating physician. 3. Acute kidney injury requiring any type of renal replacement therapy during the follow-up period. 4. New onset or worsening heart failure, defined as persistent (\> 24 hours from initiation) need for vasopressor/inotropic hemodynamic support, need for mechanical circulatory support after surgery, inability to close the sternotomy due to hemodynamic instability after surgery or readmission for acute heart failure during follow-up.
Number (fraction) of patients with severe post-operative complications during index admission, defined as a Clavien-Dindo class of 3 to 5.
The Clavien-Dindo classification runs from 1 to 5 with a higher score indicating more severe complications.
Number (fraction) of patients with delirium, defined as a positive Confusion Assessment Method for the ICU (CAM-ICU) or wards (CAM).
Number (fraction) of patients with delirium during index admission will be reported. Outcome will be assessed daily until hospital discharge.
Quality of Recovery-15 (QoR-15) score
The QoR-15 score includes 15 questions with each question being graded from 0-10.
Other outcomes
Surgical wound infection
Surgical wound infection including sternum infection and/or endocarditis, requiring antibiotics for \> 48 hours and/or surgical revision.
Sepsis
Sepsis, as defined by the Sepsis-3 criteria, requiring antibiotics for a minimum of 3 consecutive days. 3\)
Acute kidney injury
Acute kidney injury, as defined by the KDIGO criteria.
Myocardial infarction
Myocardial infarction, as defined by the Fourth Universal Definition of Myocardial Infarction.
Sponsors and contacts
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