Postoperative delirium and cognitive decline in male and female participants aged 70+ scheduled for open heart surgery
Conditions
Interventions
Product Name: Dexmedetomidine
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: DEXMEDETOMIDINE
CAS Number: 113775-47-6
Concentration unit: µg/µl microgram(s)/microlitre
Concentration ty
Sponsors
Oslo University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: • Participant must be =70 years old at the time of signing the informed consent. • Participant must be accepted for cardiac surgery with cardiopulmonary bypass. The surgical procedures may constitute 1) coronary bypass grafting, 2) tricuspid, mitral, or aortic valve replacement or repair, 3) surgery on the ascending aorta, and 4) the combination of any of these procedures • Participant must be capable of giving signed informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 900
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: • Preoperative delirium • Known hypersensitivity to the active ingredient or components of the product • Bradycardia due to sick-sinus-syndrome, 2nd or 3rd degree AV-block (if not treated with pacemaker) or any other reason causing HR <50 bpm at time of inclusion • Ischemic stroke or transitory ischemic attack the last month or critical peripheral ischemia • Acute coronary syndrome last 24 hours. Acute coronary syndrome is defined according to international guidelines • Left ventricular ejection fraction < 40% • Severe renal impairment with expected requirement for renal replacement therapy • Severe hepatic dysfunction (liver enzyme three times the upper limit of normal together with a serum albumin concentration below the normal reference limit) • Reduced peripheral autonomous activity (e.g. spinal cord injury) • Current use of tricyclic antidepressants, monoamine reuptake inhibitors or ciclosporin • Endocarditis or sepsis • Planned deep hypothermia and circulatory arrest • Emergency surgery, defined as less than 24 hours from admission to surgery • Previously included in this study • Not speaking or reading Norwegian • Any other condition as evaluated by the treating physician
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the trial is to prevent postoperative delirium;Secondary Objective: • To prevent coma or postoperative (p.o.) delirium • To reduce the duration of p.o. delirium and delirium severity • To prevent cognitive decline and reduced patient rated health status 1 and 6 months p.o. • To prevent a p.o. increase in biomarkers of neuronal injury • To estimate the associations of preoperative frailty status and the other endpoints described above • To estimate the associations of preoperative frailty status and risk for adverse effects of dexmedetomidine and clonidine treatment • To assess preoperative frailty status as a predictive marker of effect or of adverse effects of dexmedetomidine and clonidine treatment • To compare the tolerability and safety of clonidine and dexmedetomidine with placebo and with each other • To prevent progression of frailty 1 and 6 months p.o. • To assess p.o delirium as a risk factor for progression of frailty status 1 and 6 months p.o.;Primary end point(s): Cumulative incidence of postoperative delirium, as diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria;Timepoint(s) of evaluation of this end point: Postoperative delirium assessments will start as soon as possible after admission to the ICU, and will continue daily until the seventh postoperative day or until discharge from the university hospital, whichever happens first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Incidence of coma or postoperative delirium, as measured by Richmond Agitation Sedation Scale (RASS) and according to DSM-5 criteria • Incidence of death, coma or postoperative delirium, as described above • Number of delirium days postoperatively, as diagnosed according to DSM-5 criteria • Delirium severity, as measured by Confusion Assessment Method for Intensive Care Units-7 (CAM-ICU)-7, Observational Scale of Level of Arousal (OSLA) and RASS • Motor activity patterns, assessed with body worn accelerometers • Change in cognitive function between inclusion and after 1 and 6 months, as graded by Montreal Cognitive Assessment (MoCA), 10-words memory task from The Consortium Establish a Registry for Alzheimer’s Disease (CERAD), digit span tests, Trail making tests (TMT) A and B, semantic and phonemic verbal fluency, and measured repeatedly preoperatively and 1 and 6 months after surgery. • Change in patient rated health status between inclusion and after 1 and 6 months, as assessed by the EQ-5D-5L questionnaire preoperatively and 1 and 6 months postoperatively • Comparison to inclusion of serum concentrations of neurofilament light (NFL) and p-tau181 1, 3 and 5 days postoperatively • Estimate associations between frailty and the other endpoints, as described above • Safety and tolerability as determined by the numbers of Adverse Events (AEs), serious AEs (SAEs) and suspected unexpected serious adverse reactions (SUSARs), and vital signs; blood pressure (BP), heart rate (HR), peripheral oxygen saturation (SpO2) postoperatively • Interaction between preoperative frailty and treatment on delirium and the other endpoints, as described above • Change in frailty status between inclusion and after 1 and 6 months, as graded by the frailty index (FI) and essential frailty toolset (EFT) (section 8.1.3), and measured repeatedly preoperatively and 1 and 6 months after surgery • Comparison of change in frailty status between inclusion and after 1 and 6 | — |
Countries
Norway
Contacts
Public ContactDepartment of Geriatric medicine
Oslo University Hospital
Outcome results
None listed