DeliriumPhase 4ALPHA2PREVENTNCT05029050
Dexmedetomidine or Clonidine Infusion for Prevention of Delirium After Open Heart Surgery
A Phase 4 study testing Dexmedetomidine, Clonidine and Natriumchlorid in people with Delirium and Cognitive Decline, run by Oslo University Hospital at 5 sites in Norway.
Trial 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… Read more about this study
- Who is it for?
- Ages 70 years and older
- Conditions the study is for
- Delirium, Cognitive Decline, Frailty
- What is being tested?
- Dexmedetomidine, Clonidine and Natriumchlorid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 900 participants
- Where
- 5 sitesNorway
- Study dates
- 17 Jan 2022to Jan 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 70 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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.
Who cannot join
- 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
- 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
- Uncontrolled hypotension
- Ischemic stroke or transitory ischemic attack the last month or critical peripheral ischemia
Show all 19Show fewer
- 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
- Previously included in this study
- Not speaking or reading Norwegian
- Any other condition as evaluated by the treating physician
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Norway5 sites, 5 recruiting
- Recruiting
Haukeland University Hospital
Bergen
Øyvind Sverre Svendsen, MD, PhD
- Recruiting
Oslo University Hospital Rikshospitalet
Oslo
Hilde Margrethe Norum, MD, PhD
- Recruiting
Oslo University Hospital Ullevål
Oslo
Svein Aslak Landsverk, MD, PhD
- Recruiting
University Hospital of North Norway
Tromsø
Astrid Kristine Kjerstad, MD
- Recruiting
St Olav University Hospital
Trondheim
Nils Kristian Skjærvold, MD, PhD
About this study
Official title: Alpha 2 Adrenergic Receptor Agonists for the Prevention of Delirium and Cognitive Decline After Open Heart Surgery (ALPHA2PREVENT): Randomised Controlled Trial.
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.
Read the 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
- Being tested
- Dexmedetomidine, Clonidine, Natriumchlorid
- Keywords
- delirium, cognitive decline, frailty, heart surgery
- Medical subject headings
- Delirium, Cognitive Dysfunction, Frailty
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
Also called Dexdor, Precedex, N05C M18
Continous intravenous infusion
ClonidineDrug
Also called Catapresan, Catapressan, N02C X02
Continous intravenous infusion
NatriumchloridDrug
Also called Saline, NaCl 9mg/ml
Continous intravenous infusion NaCl
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Natriumchlorid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Postoperative delirium
Cumulative incidence of postoperative delirium, as diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria
Measured: Up to 7 days
Secondary outcomes (13)
Incidence of coma
Incidence of coma, as measured by Richmond Agitation Sedation Scale (-5 to +5)
Measured: Up to 7 days
Incidence of death, coma or postoperative delirium
Incidence of death, coma or postoperative delirium, as described above
Measured: Up to 7 days
Number of delirium days postoperatively
Number of delirium days postoperatively, as diagnosed according to DSM-5 criteria
Measured: Up to 7 days
Delirium severity
Delirium severity, as measured by Confusion Assessment Method for Intensive Care Units-7 (CAM-ICU)-7
Measured: Up to 7 days
Motor activity patterns
Motor activity patterns, assessed with body worn accelerometers
Measured: 6 months
Change in cognitive function between inclusion and after 1 and 6 months
Change in cognitive function between inclusion and after 1 and 6 months, as graded by Montreal Cognitive Assessment (MoCA), 10-words memory task from The Consortium Establish a Registry for Alzheimer's Disease (CERAD), digit span tests, Trail making tests (TMT) A and B, semantic and phonemic verbal fluency, and measured repeatedly preoperatively and 1 and 6 months after surgery
Measured: 6 months
Change in patient rated health status between inclusion and after 1 and 6 months
Change in patient rated health status between inclusion and after 1 and 6 months, as assessed by the EQ-5D-5L questionnaire preoperatively and 1 and 6 months postoperatively
Measured: 6 months
Serum concentrations of NFL and p-tau181
Comparison to inclusion of serum concentrations of neurofilament light (NFL) and p-tau181 1, 3 and 5 days postoperatively
Measured: 5 days postoperatively
Estimate associations between frailty and the other endpoints
Estimate associations between frailty and the other endpoints, as described above
Measured: 6 months
Safety and tolerability
Safety and tolerability as determined by the numbers of Adverse Events (AEs), serious AEs (SAEs) and suspected unexpected serious adverse reactions (SUSARs), and vital signs; blood pressure (BP), heart rate (HR), peripheral oxygen saturation (SpO2) postoperatively
Measured: 6 months
Interaction between preoperative frailty and treatment on delirium and the other endpoints
Interaction between preoperative frailty and treatment on delirium and the other endpoints, as described above
Measured: 6 months
Change in frailty status between inclusion and after 1 and 6 months
Change in frailty status between inclusion and after 1 and 6 months, as graded by the frailty index (FI) and essential frailty toolset (EFT) (section 8.1.3), and measured repeatedly preoperatively and 1 and 6 months after surgery
Measured: 6 months
Comparison of change in frailty status between inclusion and after 1 and 6 months
Comparison of change in frailty status between inclusion and after 1 and 6 months (as described above) between patients with or without postoperative delirium.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2021
- Study start17 Jan 2022
- Primary completionJul 2024 (estimated)
- Study completionJan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for DeliriumStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 900 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Haukeland University Hospital, University Hospital of North Norway, UMC Utrecht, Sahlgrenska University Hospital, St. Olavs Hospital
- Responsible party
- Principal investigator, Bjørn Erik Neerland, MD, Oslo University Hospital
- Investigators
- Bjørn Erik Neerland, PhD, Principal investigator, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05029050
- Sponsor's protocol ID
- 2021-001645-12
- Other IDs
- 2021-001645-12
- Acronym
- ALPHA2PREVENT
- Status last verified
- Apr 2024
- First submitted
- 21 Aug 2021
- Last updated
- 30 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
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.
PubMed 35725264
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Alpha 2 Adrenergic Receptor Agonists for the Prevention of Delirium and Cognitive Decline After Open Heart Surgery (ALPHA2PREVENT): Randomised Controlled Trial.
- ClinicalTrials.gov ID
- NCT05029050
- Acronym / sponsor ID
- ALPHA2PREVENT / 2021-001645-12
- Conditions
- Delirium, Cognitive Decline, Frailty
- Keywords
- delirium, cognitive decline, frailty, heart surgery
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 900 participants (estimated)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Collaborators
- Haukeland University Hospital, University Hospital of North Norway, UMC Utrecht, Sahlgrenska University Hospital, St. Olavs Hospital
- Study start
- 17 Jan 2022 (actual)
- Primary completion
- Jul 2024 (estimated)
- Study completion
- Jan 2025 (estimated)
- First posted
- 31 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Dexmedetomidine (D) | Experimental | Drug: DexmedetomidineContinuous 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. |
| Clonidine (C) | Experimental | Drug: ClonidineContinuous 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. |
| Placebo (P) | Placebo comparator | Drug: NatriumchloridContinuous 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. |
Who may qualify
- Ages
- 70 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (19 listed)
- Preoperative delirium
- Known hypersensitivity to the active ingredient or components of the product
- 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
- Uncontrolled hypotension
- Ischemic stroke or transitory ischemic attack the last month or critical peripheral ischemia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexmedetomidineAlso: Dexdor, Precedex, N05C M18Continous intravenous infusion | Drug | Dexmedetomidine (D) |
| ClonidineAlso: Catapresan, Catapressan, N02C X02Continous intravenous infusion | Drug | Clonidine (C) |
| NatriumchloridAlso: Saline, NaCl 9mg/mlContinous intravenous infusion NaCl | Drug | Placebo (P) |
Primary outcome
Postoperative delirium
Time frame: Up to 7 days
Cumulative incidence of postoperative delirium, as diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria
13 secondary outcomes
Incidence of coma
Time frame: Up to 7 days
Incidence of death, coma or postoperative delirium
Time frame: Up to 7 days
Number of delirium days postoperatively
Time frame: Up to 7 days
Delirium severity
Time frame: Up to 7 days
Motor activity patterns
Time frame: 6 months
Change in cognitive function between inclusion and after 1 and 6 months
Time frame: 6 months
Change in patient rated health status between inclusion and after 1 and 6 months
Time frame: 6 months
Serum concentrations of NFL and p-tau181
Time frame: 5 days postoperatively
Estimate associations between frailty and the other endpoints
Time frame: 6 months
Safety and tolerability
Time frame: 6 months
Interaction between preoperative frailty and treatment on delirium and the other endpoints
Time frame: 6 months
Change in frailty status between inclusion and after 1 and 6 months
Time frame: 6 months
Comparison of change in frailty status between inclusion and after 1 and 6 months
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2024.
- Derived from this study: PubMed 35725264Neerland 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.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bjørn Erik Neerland, PhD principal investigator
Oslo University Hospital
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dexmedetomidine, Clonidine and Natriumchlorid in people with Delirium and Cognitive Decline, run by Oslo University Hospital at 5 sites in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Bjørn Erik Neerland, PhD (+4790078979, bjonee@ous-hf.no), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Postoperative delirium (time frame: Up to 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05029050, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2024.