Ignite Creation Date:
2025-12-24 @ 5:16 PM
Ignite Modification Date:
2025-12-29 @ 5:39 AM
Study NCT ID:
NCT05029050
Status:
RECRUITING
Last Update Posted:
2024-04-30
First Post:
2021-08-21
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Dexmedetomidine or Clonidine Infusion for Prevention of Delirium After Open Heart Surgery
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003693', 'term': 'Delirium'}, {'id': 'D060825', 'term': 'Cognitive Dysfunction'}, {'id': 'D000073496', 'term': 'Frailty'}], 'ancestors': [{'id': 'D003221', 'term': 'Confusion'}, {'id': 'D019954', 'term': 'Neurobehavioral Manifestations'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D019965', 'term': 'Neurocognitive Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}, {'id': 'D003072', 'term': 'Cognition Disorders'}, {'id': 'D010335', 'term': 'Pathologic Processes'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D020927', 'term': 'Dexmedetomidine'}, {'id': 'D003000', 'term': 'Clonidine'}, {'id': 'D012965', 'term': 'Sodium Chloride'}], 'ancestors': [{'id': 'D007093', 'term': 'Imidazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D048288', 'term': 'Imidazolines'}, {'id': 'D002712', 'term': 'Chlorides'}, {'id': 'D006851', 'term': 'Hydrochloric Acid'}, {'id': 'D017606', 'term': 'Chlorine Compounds'}, {'id': 'D007287', 'term': 'Inorganic Chemicals'}, {'id': 'D017670', 'term': 'Sodium Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '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.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 900}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2022-01-17', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-04', 'completionDateStruct': {'date': '2025-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-04-29', 'studyFirstSubmitDate': '2021-08-21', 'studyFirstSubmitQcDate': '2021-08-25', 'lastUpdatePostDateStruct': {'date': '2024-04-30', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2021-08-31', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-07', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Additional biomarkers', 'timeFrame': '5 days postoperatively', 'description': 'Additional biomarkers of neural injury, inflammation or neurotransmission may be explored'}], 'primaryOutcomes': [{'measure': 'Postoperative delirium', 'timeFrame': 'Up to 7 days', 'description': 'Cumulative incidence of postoperative delirium, as diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria'}], 'secondaryOutcomes': [{'measure': 'Incidence of coma', 'timeFrame': 'Up to 7 days', 'description': 'Incidence of coma, as measured by Richmond Agitation Sedation Scale (-5 to +5)'}, {'measure': 'Incidence of death, coma or postoperative delirium', 'timeFrame': 'Up to 7 days', 'description': 'Incidence of death, coma or postoperative delirium, as described above'}, {'measure': 'Number of delirium days postoperatively', 'timeFrame': 'Up to 7 days', 'description': 'Number of delirium days postoperatively, as diagnosed according to DSM-5 criteria'}, {'measure': 'Delirium severity', 'timeFrame': 'Up to 7 days', 'description': 'Delirium severity, as measured by Confusion Assessment Method for Intensive Care Units-7 (CAM-ICU)-7'}, {'measure': 'Motor activity patterns', 'timeFrame': '6 months', 'description': 'Motor activity patterns, assessed with body worn accelerometers'}, {'measure': 'Change in cognitive function between inclusion and after 1 and 6 months', 'timeFrame': '6 months', 'description': "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"}, {'measure': 'Change in patient rated health status between inclusion and after 1 and 6 months', 'timeFrame': '6 months', 'description': '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'}, {'measure': 'Serum concentrations of NFL and p-tau181', 'timeFrame': '5 days postoperatively', 'description': 'Comparison to inclusion of serum concentrations of neurofilament light (NFL) and p-tau181 1, 3 and 5 days postoperatively'}, {'measure': 'Estimate associations between frailty and the other endpoints', 'timeFrame': '6 months', 'description': 'Estimate associations between frailty and the other endpoints, as described above'}, {'measure': 'Safety and tolerability', 'timeFrame': '6 months', 'description': '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'}, {'measure': 'Interaction between preoperative frailty and treatment on delirium and the other endpoints', 'timeFrame': '6 months', 'description': 'Interaction between preoperative frailty and treatment on delirium and the other endpoints, as described above'}, {'measure': 'Change in frailty status between inclusion and after 1 and 6 months', 'timeFrame': '6 months', 'description': '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'}, {'measure': 'Comparison of change in frailty status between inclusion and after 1 and 6 months', 'timeFrame': '6 months', 'description': 'Comparison of change in frailty status between inclusion and after 1 and 6 months (as described above) between patients with or without postoperative delirium.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['delirium', 'cognitive decline', 'frailty', 'heart surgery'], 'conditions': ['Delirium', 'Cognitive Decline', 'Frailty']}, 'referencesModule': {'references': [{'pmid': '35725264', 'type': 'DERIVED', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nThe 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.\n\nALPHA2PREVENT 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['OLDER_ADULT'], 'minimumAge': '70 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\nParticipants are eligible to be included in the study only if all of the following criteria apply:\n\n1. Participant must be ≥70 years old at the time of signing the informed consent.\n2. 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.\n3. Participant must be capable of giving signed informed consent.\n\n Exclusion Criteria:\n\n Participants are excluded from the study if any of the following criteria apply:\n4. Preoperative delirium\n5. Known hypersensitivity to the active ingredient or components of the product\n6. 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\n7. Uncontrolled hypotension\n8. Ischemic stroke or transitory ischemic attack the last month or critical peripheral ischemia\n9. Acute coronary syndrome last 24 hours. Acute coronary syndrome is defined according to international guidelines\n10. Left ventricular ejection fraction \\< 40%\n11. Severe renal impairment (estimated GFR \\<20ml/min) or expected requirement for renal replacement therapy\n12. Severe hepatic dysfunction (liver enzyme three times the upper limit of normal together with a serum albumin concentration below the normal reference limit)\n13. Reduced peripheral autonomous activity (e.g. spinal cord injury)\n14. Current use of tricyclic antidepressants, monoamine reuptake inhibitors or ciclosporin\n15. Endocarditis or sepsis\n16. Pheochromocytoma\n17. Planned deep hypothermia and circulatory arrest\n18. Emergency surgery, defined as less than 24 hours from admission to surgery\n19. Previously included in this study\n20. Not speaking or reading Norwegian\n21. Any other condition as evaluated by the treating physician'}, 'identificationModule': {'nctId': 'NCT05029050', 'acronym': 'ALPHA2PREVENT', 'briefTitle': 'Dexmedetomidine or Clonidine Infusion for Prevention of Delirium After Open Heart Surgery', 'organization': {'class': 'OTHER', 'fullName': 'Oslo University Hospital'}, 'officialTitle': 'Alpha 2 Adrenergic Receptor Agonists for the Prevention of Delirium and Cognitive Decline After Open Heart Surgery (ALPHA2PREVENT): Randomised Controlled Trial.', 'orgStudyIdInfo': {'id': '2021-001645-12'}, 'secondaryIdInfos': [{'id': '2021-001645-12', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Dexmedetomidine (D)', 'description': '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.', 'interventionNames': ['Drug: Dexmedetomidine']}, {'type': 'EXPERIMENTAL', 'label': 'Clonidine (C)', 'description': '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.', 'interventionNames': ['Drug: Clonidine']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo (P)', 'description': '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.', 'interventionNames': ['Drug: Natriumchlorid']}], 'interventions': [{'name': 'Dexmedetomidine', 'type': 'DRUG', 'otherNames': ['Dexdor', 'Precedex', 'N05C M18'], 'description': 'Continous intravenous infusion', 'armGroupLabels': ['Dexmedetomidine (D)']}, {'name': 'Clonidine', 'type': 'DRUG', 'otherNames': ['Catapresan', 'Catapressan', 'N02C X02'], 'description': 'Continous intravenous infusion', 'armGroupLabels': ['Clonidine (C)']}, {'name': 'Natriumchlorid', 'type': 'DRUG', 'otherNames': ['Saline', 'NaCl 9mg/ml'], 'description': 'Continous intravenous infusion NaCl', 'armGroupLabels': ['Placebo (P)']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Bergen', 'status': 'RECRUITING', 'country': 'Norway', 'contacts': [{'name': 'Øyvind Sverre Svendsen, MD, PhD', 'role': 'CONTACT'}], 'facility': 'Haukeland University Hospital', 'geoPoint': {'lat': 60.39299, 'lon': 5.32415}}, {'city': 'Oslo', 'status': 'RECRUITING', 'country': 'Norway', 'contacts': [{'name': 'Hilde Margrethe Norum, MD, PhD', 'role': 'CONTACT'}], 'facility': 'Oslo University Hospital Rikshospitalet', 'geoPoint': {'lat': 59.91273, 'lon': 10.74609}}, {'city': 'Oslo', 'status': 'RECRUITING', 'country': 'Norway', 'contacts': [{'name': 'Svein Aslak Landsverk, MD, PhD', 'role': 'CONTACT'}], 'facility': 'Oslo University Hospital Ullevål', 'geoPoint': {'lat': 59.91273, 'lon': 10.74609}}, {'city': 'Tromsø', 'status': 'RECRUITING', 'country': 'Norway', 'contacts': [{'name': 'Astrid Kristine Kjerstad, MD', 'role': 'CONTACT'}], 'facility': 'University Hospital of North Norway', 'geoPoint': {'lat': 69.6489, 'lon': 18.95508}}, {'city': 'Trondheim', 'status': 'RECRUITING', 'country': 'Norway', 'contacts': [{'name': 'Nils Kristian Skjærvold, MD, PhD', 'role': 'CONTACT'}], 'facility': 'St Olav University Hospital', 'geoPoint': {'lat': 63.43049, 'lon': 10.39506}}], 'centralContacts': [{'name': 'Bjørn Erik Neerland, PhD', 'role': 'CONTACT', 'email': 'bjonee@ous-hf.no', 'phone': '+4790078979'}, {'name': 'Torgeir Bruun Wyller, Professor', 'role': 'CONTACT', 'email': 't.b.wyller@medisin.uio.no', 'phone': '+4791166682'}], 'overallOfficials': [{'name': 'Bjørn Erik Neerland, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Oslo University Hospital'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'YES'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Oslo University Hospital', 'class': 'OTHER'}, 'collaborators': [{'name': 'Haukeland University Hospital', 'class': 'OTHER'}, {'name': 'University Hospital of North Norway', 'class': 'OTHER'}, {'name': 'UMC Utrecht', 'class': 'OTHER'}, {'name': 'Sahlgrenska University Hospital', 'class': 'OTHER'}, {'name': 'St. Olavs Hospital', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Medical doctor, postdoctoral researcher', 'investigatorFullName': 'Bjørn Erik Neerland, MD', 'investigatorAffiliation': 'Oslo University Hospital'}}}}