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

NCT ID: NCT05029050

Last Updated: 2024-04-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 900 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-17
• Study Completion Date: 2025-01-31

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.

Detailed 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.

Conditions

Delirium; Cognitive Decline; Frailty

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Dexmedetomidine (D)

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.

Group Type: EXPERIMENTAL

Dexmedetomidine

Intervention Type: DRUG

Continous intravenous infusion

Clonidine (C)

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.

Group Type: EXPERIMENTAL

Clonidine

Intervention Type: DRUG

Continous intravenous infusion

Placebo (P)

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.

Group Type: PLACEBO_COMPARATOR

Natriumchlorid

Intervention Type: DRUG

Continous intravenous infusion NaCl

Interventions

Dexmedetomidine

Continous intravenous infusion

Intervention Type: DRUG

Clonidine

Continous intravenous infusion

Intervention Type: DRUG

Natriumchlorid

Continous intravenous infusion NaCl

Intervention Type: DRUG

Other Intervention Names

Dexdor; Precedex; N05C M18; Catapresan; Catapressan; N02C X02; Saline; NaCl 9mg/ml

Eligibility Criteria

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

• Minimum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Haukeland University Hospital

OTHER

Sponsor Role: collaborator

University Hospital of North Norway

OTHER

Sponsor Role: collaborator

UMC Utrecht

OTHER

Sponsor Role: collaborator

Sahlgrenska University Hospital

OTHER

Sponsor Role: collaborator

St. Olavs Hospital

OTHER

Sponsor Role: collaborator

Oslo University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Bjørn Erik Neerland, MD

Medical doctor, postdoctoral researcher

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bjørn Erik Neerland, PhD

Role: PRINCIPAL_INVESTIGATOR

Oslo University Hospital

Locations

Haukeland University Hospital

Bergen, , Norway

Site Status: RECRUITING

Oslo University Hospital Rikshospitalet

Oslo, , Norway

Site Status: RECRUITING

Oslo University Hospital Ullevål

Oslo, , Norway

Site Status: RECRUITING

University Hospital of North Norway

Tromsø, , Norway

Site Status: RECRUITING

St Olav University Hospital

Trondheim, , Norway

Site Status: RECRUITING

Countries

Norway

Central Contacts

Bjørn Erik Neerland, PhD

Role: CONTACT

bjonee@ous-hf.no

+4790078979

Torgeir Bruun Wyller, Professor

Role: CONTACT

t.b.wyller@medisin.uio.no

+4791166682

Facility Contacts

Øyvind Sverre Svendsen, MD, PhD

Role: primary

Hilde Margrethe Norum, MD, PhD

Role: primary

Svein Aslak Landsverk, MD, PhD

Role: primary

Astrid Kristine Kjerstad, MD

Role: primary

Nils Kristian Skjærvold, MD, PhD

Role: primary

References

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.

Reference Type: DERIVED

PMID: 35725264 (View on PubMed)

Other Identifiers

2021-001645-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2021-001645-12

Identifier Type: -

Identifier Source: org_study_id