Dexamethasone, Olanzapine, Flow-targeted Versus Pressure-targeted Hemodynamic Management, and Low Tidal Volume Ventilation in Patients Undergoing On-pump Cardiac Surgery - a Multifactorial Design Randomized Trial

2021-HJEPharma-002

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

2022-11-10

2027-12-01

2027-12-01

Recruiting

1200

Inclusion Criteria: 1. Adult, i.e., above 18 years of age 2. Scheduled for CABG and/or AVR, irrespective of other concomitant valve surgery. Exclusion Criteria: 1. Acute surgery (i.e. off hours surgery) 2. Pregnancy or currently breastfeeding. Pregnancy in all fertile women will be ruled out by pregnancy testing prior to randomization. 3. Known endocarditis at time of screening 4. Previous participation in the trial 5. Active infection, including bacterial, viral, and/or fungal infection 6. Known hepatic cirrhosis 7. Known severe thrombocytopenia with thrombocyte levels \< 50 x 109/L 8. Known severe neutropenia with neutrocyte levels \< 2 x 109/L 9. On the waiting list for a heart transplant 10. Recipient of any major organ transplant 11. Obstructive hypertrophic cardiomyopathy, active myocarditis, constrictive pericarditis, untreated hypothyroidism or hyperthyroidism 12. Having received cytotoxic/cytostatic chemotherapy or radiation therapy for treatment of malignancy within the last 6 months. 13. Clinical evidence of current malignancy except for basal or localized squamous cell carcinoma, cervical intraepithelial neoplasia or stable prostate cancer. 14. Known narrow-angle glaucoma 15. Known phenylketonuria 16. Type I diabetes 17. Known long QT syndrome 18. Known allergy for any of the included study drugs 19. Any condition, where participation in the study, in the investigator's opinion could put the subject at risk, confound the study results or interfere significantly with participation in the study Patients with extracardiac arteriopathy (assessed as part of the pre-operative EuroSCORE) will be excluded from the intervention 'flow-targeted vs. pressure-targeted hemodynamic management during CPB'.

{'studyType': 'INTERVENTIONAL', 'phases': ['NA'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'FACTORIAL', 'interventionModelDescription': 'The trial assumes a priori that any effect of each of the four interventions are independent from any effect of another intervention.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'TRIPLE', 'maskingDescription': 'The dexamethasone intervention will be carried out by the nurse anesthetist and the perfusionist, and accordingly will be un-blinded. The perfusionists and the nurse anaesthetist will not be involved in any postoperative clinical care, outcome evaluation, or data analyses. The participant, trial staff, and all clinical personnel with the exception of the nurse anaesthetist and perfusionist will be blinded.\n\nThe olanzapine intervention will be blinded for all; including the participant, trial staff, and all clinical personnel.\n\nThe hemodynamic and ventilatory strategy interventions will be unblinded for the staff in the operating theatre (OR). The interventions will be blinded for the participants, trial staff and clinical personnel outside the OR.', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 1200, 'type': 'ESTIMATED'}}

2024-01-12