Alpha-2-adrenergic receptor agonists for the prevention of delirium and cognitive decline after open heart surgery (ALPHA2PREVENT): protocol for a multicentre randomised controlled trial
Introduction Postoperative 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 postoperat...
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BMJ Publishing Group
2022-06-01
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| Online Access: | https://bmjopen.bmj.com/content/12/6/e057460.full |
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| author | Eva Skovlund Rune Haaverstad Henrik Zetterberg Jorunn L Helbostad Rolf Busund Johan Raeder Theis Tønnessen Torgeir Bruun Wyller Melanie R Simpson Nils Kristian Skjærvold Bjørn Erik Neerland Svein Aslak Landsverk Ieva Martinaityte Hilde Margrethe Norum Geir Selbaek Elisabeth Skaar Arjen JC Slooter Øyvind Sverre Svendsen Alexander Wahba |
| author_facet | Eva Skovlund Rune Haaverstad Henrik Zetterberg Jorunn L Helbostad Rolf Busund Johan Raeder Theis Tønnessen Torgeir Bruun Wyller Melanie R Simpson Nils Kristian Skjærvold Bjørn Erik Neerland Svein Aslak Landsverk Ieva Martinaityte Hilde Margrethe Norum Geir Selbaek Elisabeth Skaar Arjen JC Slooter Øyvind Sverre Svendsen Alexander Wahba |
| author_sort | Eva Skovlund |
| collection | DOAJ |
| description | Introduction Postoperative 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 analysis This 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 dissemination This 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 number NCT05029050. |
| format | Article |
| id | doaj-art-dc402255825049c9a5e70d0adb99cc36 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2022-06-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-dc402255825049c9a5e70d0adb99cc362025-02-01T12:00:09ZengBMJ Publishing GroupBMJ Open2044-60552022-06-0112610.1136/bmjopen-2021-057460Alpha-2-adrenergic receptor agonists for the prevention of delirium and cognitive decline after open heart surgery (ALPHA2PREVENT): protocol for a multicentre randomised controlled trialEva Skovlund0Rune Haaverstad1Henrik Zetterberg2Jorunn L Helbostad3Rolf Busund4Johan Raeder5Theis Tønnessen6Torgeir Bruun Wyller7Melanie R Simpson8Nils Kristian Skjærvold9Bjørn Erik Neerland10Svein Aslak Landsverk11Ieva Martinaityte12Hilde Margrethe Norum13Geir Selbaek14Elisabeth Skaar15Arjen JC Slooter16Øyvind Sverre Svendsen17Alexander Wahba18Department of Public Health and Nursing, Norwegian University of Science and Technology NTNU, Trondheim, NorwayDepartment of Heart Disease, Haukeland University Hospital, Bergen, NorwayHong Kong Center for Neurodegenerative Diseases, Hong Kong, People`s Republic of ChinaDepartment of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, NorwayDepartment of Cardiothoracic and Vascular Surgery, Universitetssykehuset Nord-Norge, Tromso, NorwayAnaesthesiology, Oslo University, Oslo, NorwayDepartment of Cardiothoracic Surgery, Oslo University Hospital, Oslo, NorwayInstitute of Clinical Medicine, University of Oslo, Oslo, NorwayDepartment of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, NorwayDepartment of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, NorwayDepartment of Geriatric Medicine, Oslo University Hospital, Oslo, NorwayDepartment of Anaesthesiology, Oslo University Hospital, Oslo, NorwayInstitute of Clinical Medicine, UiT The Artic University of Norway, Tromsø, NorwayDepartment of Research and Development, Oslo University Hospital, Oslo, NorwayVestfold Hospital Trust, Norwegian National Centre for Ageing and Health, Tonsberg, Vestfold, Norway1 Department of Heart Disease, Haukeland University Hospital, Bergen, NorwayDepartment of Intensive Care Medicine, University Medical Centre Utrecht, Utrecht, The NetherlandsDepartment of Anesthesia and Intensive Care, Haukeland University Hospital, Bergen, NorwayDepartment of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, NorwayIntroduction Postoperative 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 analysis This 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 dissemination This 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 number NCT05029050.https://bmjopen.bmj.com/content/12/6/e057460.full |
| spellingShingle | Eva Skovlund Rune Haaverstad Henrik Zetterberg Jorunn L Helbostad Rolf Busund Johan Raeder Theis Tønnessen Torgeir Bruun Wyller Melanie R Simpson Nils Kristian Skjærvold Bjørn Erik Neerland Svein Aslak Landsverk Ieva Martinaityte Hilde Margrethe Norum Geir Selbaek Elisabeth Skaar Arjen JC Slooter Øyvind Sverre Svendsen Alexander Wahba Alpha-2-adrenergic receptor agonists for the prevention of delirium and cognitive decline after open heart surgery (ALPHA2PREVENT): protocol for a multicentre randomised controlled trial BMJ Open |
| title | Alpha-2-adrenergic receptor agonists for the prevention of delirium and cognitive decline after open heart surgery (ALPHA2PREVENT): protocol for a multicentre randomised controlled trial |
| title_full | Alpha-2-adrenergic receptor agonists for the prevention of delirium and cognitive decline after open heart surgery (ALPHA2PREVENT): protocol for a multicentre randomised controlled trial |
| title_fullStr | Alpha-2-adrenergic receptor agonists for the prevention of delirium and cognitive decline after open heart surgery (ALPHA2PREVENT): protocol for a multicentre randomised controlled trial |
| title_full_unstemmed | Alpha-2-adrenergic receptor agonists for the prevention of delirium and cognitive decline after open heart surgery (ALPHA2PREVENT): protocol for a multicentre randomised controlled trial |
| title_short | Alpha-2-adrenergic receptor agonists for the prevention of delirium and cognitive decline after open heart surgery (ALPHA2PREVENT): protocol for a multicentre randomised controlled trial |
| title_sort | alpha 2 adrenergic receptor agonists for the prevention of delirium and cognitive decline after open heart surgery alpha2prevent protocol for a multicentre randomised controlled trial |
| url | https://bmjopen.bmj.com/content/12/6/e057460.full |
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