E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The drug Dexmedetomidine will be investigated in patients (men and women) undergoing elective cardiac or abdominal surgery. The study medication will be administered perioperatively by intravenous infusion continously (at the longest 48 h) to prevent/reduce the rate of Delirium and the incidence of POCD. |
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E.1.1.1 | Medical condition in easily understood language |
The drug Dexmedetomidine will be investigated in patients (men and women) undergoing elective cardiac or abdominal surgery to prevent/reduce postoperative confusion and cognitive impairment. |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Incidence of postoperative delirium measured with the Confusion Assessment Method for the ICU (CAM-ICU)“or the „Confusion Assessment Method (CAM) and/or Chart Review and/or DSM V/ICD-10 “ |
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E.2.2 | Secondary objectives of the trial |
1.Incidence of Subsyndromal Delirium (SSD) 2.Severity of Delirium 3. Incidence of POCD incl. subjective Memory - feeling 4.Severity of anxiety (Faces Anxiety Scale)5.Management of sedation (RASS –Score)6.Management of Vigilance Glasgow Coma Scale 7.Management of analgesia and pain levels: (NRS-V or FPS-R or BPS or BPS-NI) 8.Relevant medication 9.Severity of illness (SAPS II, APACHE II, SOFA) 10.Mechanical ventilation/weaning failure 11. Cerebral oximetry 12. Processive EEG/EMG-Data(SedLine®) 13.Complete blood count, AChE-analysis 14.Cortisol-analysis 15.Organ dysfunctions 16.Infections 17.LOS-ICU 18.LOS-hospital 19.Quality of life (EuroQuol 5D (EQ-5D-Instrument)) 20.Incidence of postop. ve cognitive dysfunction (POCD) (CANTAB®, MMS) 21.Mortality 22. Sleep quality 23. Changes of hemodynamic parameters in the intraoperative transesophageal echocardiography 24. Photomotor Reflex |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Patients aged ≥ 60 years 2.Male and female patients undergoing elective cardiac (elective CABG-surgery without valve surgery with left ventricular ejection fraction ≥ 30%) or pancreatic or hepatic or intestinal or gastric surgery of both Campus Charité Mitte and Campus Virchow - Klinikum, Charité – University Medicine Berlin 3.Offered patient information and written consent by the patient (according to AMG § 40 (1) 3b) 4.Premedication only with benzodiazepines 5.Paintherapy during the operation with regional procedures and/or Sufentanil/Fentanyl 6.Anesthesia in cardioasurgery according to Heart-Lung-Apparatus 7.Anesthesia with hypnoticum Propofol 8.Paintherapy after operation according to S3-Guideline 9.Postoperative medication for anxiolysis only with benzodiazepines
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E.4 | Principal exclusion criteria |
1.Known drug intolerance/allergy: dexmedetomidine or to other ingredients 2.Lacking willingness to save and hand out pseudonymised data within the clinical trial 3.Accommodation in an institution due to an official or judicial order (according to AMG §40 (1) 4) 4. Employee of the Charité - University - Medicine Berlin CVK/CCM 5. Illiteracy 6. Inability to speak and/or read German 7. Minimal mental status examination (MMSE) < 24 8. Severe hearing loss or visual impairment 9. Acute brain injury 10. Intracranial haemorrhage within one year before participation in the study 11. Manifest psychiatric disease 12. Known illicit substance abuse 13. Acute intoxication 14. For women: Pregnancy or positive pregnancy test within the preoperative screening 15. Homeless or other circumstances, where the patient would not be reachable by telephone or postal services for the 3-months follow up 16. Participation in another interventional clinical trial according to the German Drug Law at time of inclusion and during the trial 17. Acute circulatory failure at time of randomisation (severe hypotension with mean arterial pressure < 55 mmHg despite vasopressors or optimal preload) 18. AV-conduction-block II or III (unless pacemaker installed) 19. Severe bradycardia (heart-rate < 50 bpm, preoperative, permanent) 20. Spinal cord injury with known autonomic dysregulation 21. Preoperative acute cerebrovascular event with neurologic residues 22. Liver insufficiency (Child C cirrhosis, MELD Score > 17) 23. Aplication of Remifentanil during the operation 24. Postoperatively planned deep sedation (RASS, -4 to -5) 25. Administration of Clonidin during administration of the study drug 26. Additional administration of Dexmedetomidine within 3 months after study inclusion
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of postoperative delirium measured with the Confusion Assessment Method for the ICU (CAM-ICU)“or the „Confusion Assessment Method (CAM) and/or Chart Review and/or DSM V/ICD-10 “ |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Measured until the 5th postoperative day
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E.5.2 | Secondary end point(s) |
1.Incidence of Subsyndromal Delirium (SSD) 2.Severity of Delirium 3. Incidence of POCD (Cambridge Neuropsychological Automated Test Battery CANTAB®, Minimal Mental Status Examination MMSE) including subjective Memory - feeling (Item 10 of the Geriatric Depression Scale, including limitation in usual activities (EQ-5D)) 4.Severity of anxiety (Faces Anxiety Scale FAS)5.Management of sedation (RASS –Score)6.Management of Vigilance Glasgow Coma Scale (GCS) 7.Management of analgesia and pain levels: (NRS-V or FPS-R or BPS or BPS-NI) 8.Relevant medication 9.Severity of illness (SAPS II, APACHE II, SOFA) 10.Mechanical ventilation/weaning failure 11. Cerebral Oximetry 12. Processive EEG/EMG-Data(SedLine®) 13.Complete blood count (Sysmex Parameter), AChE-analysis 14.Cortisol-analysis 15.Organ dysfunctions 16.Infections (CDC), (SSI)) 17.LOS-ICU 18.LOS-hospital (time that discharge criteria were met: PADSS) 19.Quality of life (EuroQuol 5D (EQ-5D-Instrument)) 20.Incidence of postoperative cognitive dysfunction (POCD) (CANTAB®, MMS) 21.Mortality (3-month-mortality) 22. Sleep quality 23. Changes of hemodynamic parameters in the intraoperative transesophageal echocardiography (size and function of left and right ventricle; diastolic function; cardiac responsiveness to volume; heart valves and their function] 24. Photomotor Reflex
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Measured: 1-2and 5-6 and 8-10 until the 5th postoperative day 11-12 intraoperatively until first postoperative day 13 preoperatively and until the 3rd postoperative day 14 preoperatively and until the 3rd postoperative day, at discharge and after 3 months 17-18 until the end of hospital stay 3,4 and 7 and 15-16 and 19-22 until 3 months 23 intraoperatively; 24 preoperatively at the day of operation and at discharge |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last patient last visit (of last follow up) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |