We investigate the efficacy of two pharmaceutical interventions for reducing mortality and organ damage, and shortening length of hospital stay in patients undergoing heart surgery (i.e. coronary artery bypass grafting and/or heart valve replacement). MedDRA version: 20.0 Level: LLT Classification code 10008937 Term: Chronic ischemic heart disease, unspecified System Organ Class: 10007541 - Cardiac disorders MedDRA version: 21.1 Level: PT Classification code 10061994 Term: Heart valve operatio
Conditions
Interventions
Trade Name: Dexavit
Product Name: Dexavit
Pharmaceutical Form: Solution for injection
INN or Proposed INN: DEXAMETHASONE PHOSPHATE
CAS Number: 312-93-6
Concentration unit: mg/ml milligram(s)/millilitr
Sponsors
Rigshospitalet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Adult, i.e., above 18 years of age 2) Scheduled for CABG and/or AVR, irrespective of other concomitant valve surgery. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 400 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 800
Exclusion criteria
Exclusion criteria: 1) Acute surgery (i.e. off hours surgery) 2) Pregnancy or currently breastfeeding 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 Specific exclusion criteria 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’.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is to determine the efficacy of dexamethasone compared with placebo on the primary endpoint days alive outside hospital within 90 days in adult subjects undergoing elective or subacute isolated CABG, isolated AVR, or CABG plus any concomitant valve surgery. The coprimary objectives are to determine the efficacy of olanzapine versus placebo administered preoperatively, the efficacy of flow-targeted versus pressure-targeted hemodynamic management during CPB, and the efficacy of low tidal volume ventilation versus no ventilation during CPB, on the endpoint days alive outside hospital within 90 days in adult subjects undergoing elective or subacute isolated CABG, isolated AVR, or CABG plus any concomitant valve surgery.;Secondary Objective: The secondary objectives of this trial are to determine the efficacy of the interventions on mortality as well as morbidity assessed by either manifest organ damage or by surrogate markers (ex. biomarkers) of organ damage. ;Primary end point(s): The primary endpoint will be number of days alive and outside hospital within 90 days after surgery.;Timepoint(s) of evaluation of this end point: 90 days after surgery | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Time in days to occurrence of any component in a composite secondary endpoint during follow-up (6 months after last included subject) consisting of a) Death from any cause b) 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. c) Acute kidney injury requiring any type of renal replacement therapy during the follow-up period. d) 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. 2) Severe post-operative complications during index admission, defined as a Clavien-Dindo class of 3 to 5. 3) Delirium during the first 7 days after surgery, defined as a positive Confusion Assessment Method for the ICU (CAM-ICU) score or a positive Confusion Assessment Method (CAM) score for the general wards 4) Quality of Recovery-15 (QoR-15) score 3 days, or as soon as possible, after surgery 6) 90-day outcomes a) Survival b) Change in modified Rankin Scale (mRS) from baseline c) Health-related quality of life (EQ-5D-5L) d) Change in self-perceived function “two simple questions”* e) Days alive outside ICU within 90 days 7) 180-day outcomes a) Survival *) ’Two simple questions’ asked to the participant in Danish: ’Har du, inden for de sidste to uger, haft brug for hjælp fra en anden person til hverdags-aktiviteter?’ ’Føler du selv, at du er kommet dig helt efter din operation?’ ;Timepoint(s) of evaluation of this end point: Follow-up at 90 days. Registry-based mortality being assessed at 180 days. | — |
Countries
Denmark
Contacts
Public ContactDepartment of Cardiology
Rigshospitalet
Outcome results
None listed