Clonidine hydrochloride for Delirium

Inclusion criteria

• {"criterion_text":"- Participant must be ≥70 years old at the time of signing the informed consent.\n- 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 of any of these procedures.\n- Participant must be capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol."}

Exclusion criteria

• {"criterion_text":"- Preoperative delirium (present at time of potential inclusion)\n- Known hypersensitivity to the active ingredient or components of the product\n- 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\n- Uncontrolled hypotension\n- Ischemic stroke or transitory ischemic attack the last month or critical peripheral ischemia\n- Acute coronary syndrome last 24 hours. Acute coronary syndrome is defined according to international guidelines\n- Left ventricular ejection fraction < 40%\n- Severe renal impairment (estimated GFR < 20 ml/min) or expected requirement for renal replacement therapy\n- Severe hepatic dysfunction (liver enzyme three times the upper limit of normal together with a serum albumin concentration below the normal reference limit\n- Reduced peripheral autonomous activity (e.g. spinal cord injury)\n- Current use of tricyclic antidepressants, monoamine reuptake inhibitors or ciclosporin\n- Endocarditis or sepsis\n- Pheochromocytoma\n- Planned deep hypothermia and circulatory arrest\n- Emergency surgery, defined as less than 24 hours from admission to surgery\n- Previously included in this study\n- Not speaking or reading Norwegian\n- Any other condition as evaluated by the treating physician"}

Primary endpoints

• {"endpoint_text":"- Cumulative incidence of postoperative delirium, as diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria","definition_or_measurement_approach":"Diagnosed according to DSM-5 criteria"}

Secondary endpoints

• {"endpoint_text":"- Incidence of coma or postoperative delirium, as measured by Richmond Agitation Sedation Scale (RASS) and according to DSM-5 criteria","definition_or_measurement_approach":"Measured by Richmond Agitation Sedation Scale (RASS) and diagnosed according to DSM-5 criteria"}
• {"endpoint_text":"- Incidence of death, coma or postoperative delirium, as described above","definition_or_measurement_approach":"Composite incidence as described: death, coma or postoperative delirium (DSM-5/RASS)"}
• {"endpoint_text":"- Number of delirium days postoperatively, as diagnosed according to DSM-5 criteria","definition_or_measurement_approach":"Count of postoperative days with delirium diagnosed per DSM-5"}
• {"endpoint_text":"- Delirium severity, as measured by Confusion Assessment Method for Intensive Care Units-7 (CAM-ICU)-7, Observational Scale of Level of Arousal (OSLA) and RASS","definition_or_measurement_approach":"Severity measured using CAM-ICU-7, OSLA and RASS scores"}
• {"endpoint_text":"- Motor activity patterns, assessed with body worn accelerometers","definition_or_measurement_approach":"Motor activity assessed using body-worn accelerometers"}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Cognitive change measured by MoCA, CERAD 10-word task, digit span, TMT A/B, semantic and phonemic verbal fluency at baseline, 1 month and 6 months"}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"EQ-5D-5L questionnaire at baseline, 1 month and 6 months"}
• {"endpoint_text":"- Comparison to inclusion of serum concentrations of neurofilament light (NFL) and p-tau181 1, 3 and 5 days postoperatively","definition_or_measurement_approach":"Serum NFL and p-tau181 measured at baseline and at days 1, 3 and 5 postoperatively"}
• {"endpoint_text":"- Estimate associations between frailty and the other endpoints, as described above","definition_or_measurement_approach":"Statistical association analyses between preoperative frailty measures and other endpoints"}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Safety measured by counts of AEs/SAEs/SUSARs and monitoring of BP, HR, SpO2 postoperatively"}
• {"endpoint_text":"- Interaction between preoperative frailty and treatment on delirium and the other endpoints, as described above","definition_or_measurement_approach":"Interaction analyses between frailty status and treatment effects on delirium and other endpoints"}
• {"endpoint_text":"- Change in frailty status between inclusion and after 1 and 6 months, as graded by the frailty index (FI) and essential frailty toolset (EFT), and measured repeatedly preoperatively and 1 and 6 months after surgery","definition_or_measurement_approach":"Frailty measured by FI and EFT at baseline, 1 month and 6 months"}
• {"endpoint_text":"- Comparison of change in frailty status between inclusion and after 1 and 6 months (as described above) between patients with or without postoperative delirium.","definition_or_measurement_approach":"Comparison of frailty change trajectories between patients with vs without postoperative delirium"}
• {"endpoint_text":"- Comparison of changes in EEG pattern from preoperatively to postoperatively in patients who do and do not develop delirium.","definition_or_measurement_approach":"EEG pattern comparison pre- vs postoperatively stratified by delirium outcome"}
• {"endpoint_text":"- Comparison of postoperative EEG in patients who do and do not develop delirium and the association with exposure to dexmedetomidine vs clonidine vs placebo","definition_or_measurement_approach":"Postoperative EEG comparisons by delirium status and treatment arm (dexmedetomidine, clonidine, placebo)"}
• {"endpoint_text":"- Additional biomarkers of neural injury, inflammation or neurotransmission may be explored","definition_or_measurement_approach":"Exploratory biomarker analyses as specified in protocol"}
• {"endpoint_text":"- Sequential Organ Failure Assessment (SOFA) score","definition_or_measurement_approach":"SOFA score assessments postoperatively"}

Norway

Earliest CTIS Part Ii Submission Date

22-08-2024

Latest Decision Or Authorization Date

13-04-2026

Processing Time Days

599

Number Of Sites

4

Number Of Participants

900

Primary sponsor

Full Name

Oslo University Hospital HF

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Norway