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
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
BMJ open - 12(2022), 6 vom: 20. Juni, Seite e057460 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Neerland, Bjørn Erik [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.06.2022 Date Revised 16.07.2022 published: Electronic ClinicalTrials.gov: NCT05029050 Citation Status MEDLINE |
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| doi: |
10.1136/bmjopen-2021-057460 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Neerland, Bjørn Erik |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Alpha-2-adrenergic receptor agonists for the prevention of delirium and cognitive decline after open heart surgery (ALPHA2PREVENT) |b protocol for a multicentre randomised controlled trial |
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| 500 | |a Date Revised 16.07.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT05029050 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a TRIAL REGISTRATION NUMBER: NCT05029050 | ||
| 650 | 4 | |a Clinical Trial Protocol | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a adult anaesthesia | |
| 650 | 4 | |a cardiac surgery | |
| 650 | 4 | |a delirium & cognitive disorders | |
| 650 | 4 | |a geriatric medicine | |
| 650 | 7 | |a Adrenergic alpha-2 Receptor Agonists |2 NLM | |
| 650 | 7 | |a Dexmedetomidine |2 NLM | |
| 650 | 7 | |a 67VB76HONO |2 NLM | |
| 650 | 7 | |a Clonidine |2 NLM | |
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| 700 | 1 | |a Busund, Rolf |e verfasserin |4 aut | |
| 700 | 1 | |a Haaverstad, Rune |e verfasserin |4 aut | |
| 700 | 1 | |a Helbostad, Jorunn L |e verfasserin |4 aut | |
| 700 | 1 | |a Landsverk, Svein Aslak |e verfasserin |4 aut | |
| 700 | 1 | |a Martinaityte, Ieva |e verfasserin |4 aut | |
| 700 | 1 | |a Norum, Hilde Margrethe |e verfasserin |4 aut | |
| 700 | 1 | |a Ræder, Johan |e verfasserin |4 aut | |
| 700 | 1 | |a Selbaek, Geir |e verfasserin |4 aut | |
| 700 | 1 | |a Simpson, Melanie R |e verfasserin |4 aut | |
| 700 | 1 | |a Skaar, Elisabeth |e verfasserin |4 aut | |
| 700 | 1 | |a Skjærvold, Nils Kristian |e verfasserin |4 aut | |
| 700 | 1 | |a Skovlund, Eva |e verfasserin |4 aut | |
| 700 | 1 | |a Slooter, Arjen Jc |e verfasserin |4 aut | |
| 700 | 1 | |a Svendsen, Øyvind Sverre |e verfasserin |4 aut | |
| 700 | 1 | |a Tønnessen, Theis |e verfasserin |4 aut | |
| 700 | 1 | |a Wahba, Alexander |e verfasserin |4 aut | |
| 700 | 1 | |a Zetterberg, Henrik |e verfasserin |4 aut | |
| 700 | 1 | |a Wyller, Torgeir Bruun |e verfasserin |4 aut | |
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