Overview
A parallel-group treatment, five-centre, participant and investigator masked, three-arm study to assess the safety and effectiveness of dexmedetomidine or clonidine infusion compared to placebo for the prevention of delirium and cognitive decline in male and female participants aged 70+ scheduled for open heart surgery.
Description
Delirium is a major public health concern without therapeutic options. It is an acute disturbance of attention and cognition, precipitated by an acute somatic condition. Delirious patients are often subject to off-label treatment with psychotropic drugs that have dubious effects.
The intravenous alpha-2-adrenergic receptor agonist dexmedetomidine, attenuating sympathetic nervous system activity, shows promise as treatment for delirium, but its use is limited to intensive care units (ICU). Its long-term cognitive effects are unknown. Clonidine is a pharmacodynamically similar drug that can be given orally and has been used for decades as an antihypertensive agent, but is else sparsely studied.
ALPHA2PREVENT will be a three-armed randomised controlled trial to study 1) whether repurposing of clonidine can represent a novel treatment option for delirium, and 2) the possible effects of both dexmedetomidine and clonidine on long-term cognitive trajectories, motor activity patterns, patient rated outcome measures and biomarkers of neuronal injury.
Eligibility
Inclusion Criteria:
Participants are eligible to be included in the study only if all of the following criteria
apply:
1. Participant must be ≥70 years old at the time of signing the informed consent.
2. 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 any of these procedures.
3. Participant must be capable of giving signed informed consent.
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
4. Preoperative delirium
5. Known hypersensitivity to the active ingredient or components of the product
6. 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
7. Uncontrolled hypotension
8. Ischemic stroke or transitory ischemic attack the last month or critical peripheral
ischemia
9. Acute coronary syndrome last 24 hours. Acute coronary syndrome is defined according to
international guidelines
10. Left ventricular ejection fraction < 40%
11. Severe renal impairment (estimated GFR <20ml/min) or expected requirement for renal
replacement therapy
12. Severe hepatic dysfunction (liver enzyme three times the upper limit of normal
together with a serum albumin concentration below the normal reference limit)
13. Reduced peripheral autonomous activity (e.g. spinal cord injury)
14. Current use of tricyclic antidepressants, monoamine reuptake inhibitors or ciclosporin
15. Endocarditis or sepsis
16. Pheochromocytoma
17. Planned deep hypothermia and circulatory arrest
18. Emergency surgery, defined as less than 24 hours from admission to surgery
19. Previously included in this study
20. Not speaking or reading Norwegian
21. Any other condition as evaluated by the treating physician