Dexmedetomidine or Clonidine Infusion for Prevention of Delirium After Open Heart Surgery

NCT05029050 | Recruiting Phase 4 DMC

• 1 other identifier: 2021-001645-12
• Study Type: interventional
• Target: 900
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Delirium; Cognitive Decline; Frailty

Keywords

delirium; cognitive decline; frailty; heart surgery

Outcome Measures

Primary Outcomes (1)

• Postoperative delirium

  Cumulative incidence of postoperative delirium, as diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria

  Up to 7 days

Secondary Outcomes (13)

• Incidence of coma

  Up to 7 days

• Incidence of death, coma or postoperative delirium

  Up to 7 days

• Number of delirium days postoperatively

  Up to 7 days

• Delirium severity

  Up to 7 days

• Motor activity patterns

  6 months

Other Outcomes (1)

• Additional biomarkers

  5 days postoperatively

Study Arms (3)

Dexmedetomidine (D)

EXPERIMENTAL

Continuous intravenous infusion of dexmedetomidine 0.4 μg/kg/hour from the start of cardiopulmonary bypass and during surgery, followed by 0.2 μg/kg/hour until discharge from the ICU or 24 hours postoperatively, whichever happens first.

Drug: Dexmedetomidine

Clonidine (C)

EXPERIMENTAL

Continuous intravenous infusion of clonidine 0.4 μg/kg/hour from the start of cardiopulmonary bypass and during surgery, followed by 0.2 μg/kg/hour until discharge from the ICU or 24 hours postoperatively, whichever happens first.

Drug: Clonidine

Placebo (P)

PLACEBO COMPARATOR

Continuous intravenous infusion of saline 0.4 μg/kg/hour from the start of cardiopulmonary bypass and during surgery, followed by 0.2 μg/kg/hour until discharge from the ICU or 24 hours postoperatively, whichever happens first.

Drug: Natriumchlorid

Interventions

Dexmedetomidine DRUG

Continous intravenous infusion

Also known as: Dexdor, Precedex, N05C M18

Dexmedetomidine (D)

Clonidine DRUG

Continous intravenous infusion

Also known as: Catapresan, Catapressan, N02C X02

Clonidine (C)

Natriumchlorid DRUG

Continous intravenous infusion NaCl

Also known as: Saline, NaCl 9mg/ml

Placebo (P)

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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 any of these procedures.
• Participant must be capable of giving signed informed consent.

You may not qualify if:

• 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
• Uncontrolled hypotension
• 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 (estimated GFR \<20ml/min) or 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
• Pheochromocytoma
• Planned deep hypothermia and circulatory arrest
• Emergency surgery, defined as less than 24 hours from admission to surgery

Sponsors & Collaborators

• Oslo University Hospital: lead
• Haukeland University Hospital: collaborator
• University Hospital of North Norway: collaborator
• UMC Utrecht: collaborator
• Sahlgrenska University Hospital: collaborator
• St. Olavs Hospital: collaborator

Study Sites (5)

Haukeland University Hospital

Bergen, Norway

RECRUITING

Oslo University Hospital Rikshospitalet

Oslo, Norway

RECRUITING

Oslo University Hospital Ullevål

Oslo, Norway

RECRUITING

University Hospital of North Norway

Tromsø, Norway

RECRUITING

St Olav University Hospital

Trondheim, Norway

RECRUITING

Related Publications (1)

• Neerland BE, Busund R, Haaverstad R, Helbostad JL, Landsverk SA, Martinaityte I, Norum HM, Raeder J, Selbaek G, Simpson MR, Skaar E, Skjaervold NK, Skovlund E, Slooter AJ, Svendsen OS, Tonnessen T, Wahba A, Zetterberg H, Wyller TB. 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. 2022 Jun 20;12(6):e057460. doi: 10.1136/bmjopen-2021-057460.

  PMID: 35725264 DERIVED

MeSH Terms

Conditions

Delirium; Cognitive Dysfunction; Frailty

Interventions

Dexmedetomidine; Clonidine; Sodium Chloride

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Pathologic Processes

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Imidazolines; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Bjørn Erik Neerland, PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bjørn Erik Neerland, PhD

CONTACT

+4790078979; bjonee@ous-hf.no

Torgeir Bruun Wyller, Professor

CONTACT

+4791166682; t.b.wyller@medisin.uio.no

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical doctor, postdoctoral researcher

Model Details: 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.

Study Record Dates

• First Submitted: August 21, 2021
• First Posted: August 31, 2021
• Study Start: January 17, 2022
• Primary Completion: July 1, 2024
• Study Completion: January 1, 2025
• Last Updated: April 30, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share

Locations

NO (5)