Alpha-2-adrenergic receptor agonists for the prevention of delirium and cognitive decline after open heart surgery (ALPHA2PREVENT)
| Autor: | Bjørn Erik Neerland, Rolf Busund, Rune Haaverstad, Jorunn L Helbostad, Svein Aslak Landsverk, Ieva Martinaityte, Hilde Margrethe Norum, Johan Ræder, Geir Selbaek, Melanie R Simpson, Elisabeth Skaar, Nils Kristian Skjærvold, Eva Skovlund, Arjen JC Slooter, Øyvind Sverre Svendsen, Theis Tønnessen, Alexander Wahba, Henrik Zetterberg, Torgeir Bruun Wyller |
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| Přispěvatelé: | Vrije Universiteit Brussel, Clinical sciences, Neuroprotection & Neuromodulation |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Frailty
Delirium Dexmedetomidine/therapeutic use General Medicine Clonidine Cardiac Surgical Procedures/adverse effects Adrenergic alpha-2 Receptor Agonists/therapeutic use Double-Blind Method Frailty/complications Delirium/diagnosis Adrenergic alpha-2 Receptor Agonists Humans Multicenter Studies as Topic Cognitive Dysfunction Cognitive Dysfunction/etiology Cardiac Surgical Procedures Clonidine/therapeutic use Dexmedetomidine Aged Randomized Controlled Trials as Topic |
| Popis: | IntroductionPostoperative delirium is common in older cardiac surgery patients and associated with negative short-term and long-term outcomes. The alpha-2-adrenergic receptor agonist dexmedetomidine shows promise as prophylaxis and treatment for delirium in intensive care units (ICU) and postoperative settings. Clonidine has similar pharmacological properties and can be administered both parenterally and orally. We aim to study whether repurposing of clonidine can represent a novel treatment option for delirium, and the possible effects of dexmedetomidine and clonidine on long-term cognitive trajectories, motor activity patterns and biomarkers of neuronal injury, and whether these effects are associated with frailty status.Methods and analysisThis five-centre, double-blind randomised controlled trial will include 900 cardiac surgery patients aged 70+ years. Participants will be randomised 1:1:1 to dexmedetomidine or clonidine or placebo. The study drug will be given as a continuous intravenous infusion from the start of cardiopulmonary bypass, at a rate of 0.4 µg/kg/hour. The infusion rate will be decreased to 0.2 µg/kg/hour postoperatively and be continued until discharge from the ICU or 24 hours postoperatively, whichever happens first.Primary end point is the 7-day cumulative incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, fifth edition). Secondary end points include the composite end point of coma, delirium or death, in addition to delirium severity and motor activity patterns, levels of circulating biomarkers of neuronal injury, cognitive function and frailty status 1 and 6 months after surgery.Ethics and disseminationThis trial is approved by the Regional Committee for Ethics in Medical Research in Norway (South-East Norway) and by the Norwegian Medicines Agency. Dissemination plans include publication in peer-reviewed medical journals and presentation at scientific meetings.Trial registration numberNCT05029050. |
| Databáze: | OpenAIRE |
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