Neuroprotection With Dexmedetomidine in Patients Undergoing Elective Cardiac or Abdominal Surgery (Neuprodex)

Delirium Clinical Trial

Official title:

Neuroprotection With Dexmedetomidine in Patients Undergoing Elective Cardiac or Abdominal Surgery (NEUPRODEX)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02096068
• Other study ID #: Neuprodex
• Status: Completed
• Phase: Phase 4
• Start date: July 2014
• Est. completion date: July 2018

Study information

• Verified date: September 2019
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The drug Dexmedetomidine will be investigated in 72 patients (men and women) undergoing elective cardiac or abdominal surgery. The study medication will be administered perioperatively by intravenous infusion continuously (at the longest 48 h) to prevent/reduce the rate of Delirium and the incidence of postoperative cognitive deficit (POCD).

A non-surgical control group of 15 ASA II/III- patients from Berlin and surrounding area is collected for measuring the learning experience during the cognitive testings. The participants are matched on age, education, and gender to the study patients.

Cognitive testings are performed in patients of the study group (n= 72) and the control group (n= 15) to evaluate deficits in their cognitive areas (POCD (Postoperative cognitive deficit)) at three different time points up to three months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: July 2018
• Est. primary completion date: March 17, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

Study Group:

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 gastric or intestinal surgery of both Campus Charité Mitte and Campus Virchow - Klinikum, Charité - Universitätsmedizin Berlin

3. Offered patient information and written consent by the patient (according to German Drug Law § 40 (1) 3b)

4. Premedication only with benzodiazepines

5. Pain therapy during the operation with regional procedures and/or Sufentanil/Fentanyl

6. Anesthesia in cardio surgery according to Heart-Lung-Apparatus

7. Anesthesia with hypnotic agent Propofol

8. Pain therapy after operation according to S3-Guideline

9. Postoperative medication for anxiolysis only with benzodiazepines

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 - Universitätsmedizin 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. Application of Remifentanil during the operation

24. Deep sedation (RASS, -4 to -5)

25. Administration of Clonidine during administration of the study drug

26. Additional administration of Dexmedetomidine within 3 months after study inclusion

Control Group:

Inclusion Criteria:

1. Patients aged = 60 years of European descent (Caucasian)

2. Male or female patients with ASA II+III

3. ASA II+III-patients, for which no operation is planned within the next year

4. No operation in the last half year before study inclusion

5. Offered patient information and written informed consent

Exclusion Criteria

1. Minimal mental status examination (MMSE) < 24

2. Missing informed consent for saving and hand out pseudonymous data

3. Neuropsychiatric morbidity, which limits the conduction of the neurocognitive testing

4. Anacusis or Hypoacusis, which limits the conduction of the neurocognitive testing

5. Taking psychothropic drugs (including sleep-inducing drug and benzodiazepine) on a regular basis and other substances, which limit the conduction of the neurocognitive testing

Related Conditions & MeSH terms

• Cognition Disorders
• Cognitive Dysfunction
• Delirium
• Postoperative Cognitive Deficit (POCD)

Intervention

Drug:
• Dexmedetomidine (Dexdor®)
Dexmedetomidine (Dexdor 100 micrograms/ml concentrate for solution for infusion)
• 0.9% Sodium Chloride
Solution for infusion: Sodium Chloride : 9.0 g/l; Each ml contains 9 mg sodium chloride mmol/l : Na+ : 154. Cl-: 154.

Locations

Country	Name	City	State
Germany	Department of Anesthesiology and Operative Intensive Care Medicine, Campus Charité Mitte and Campus Virchow - Klinikum, Charité- Universitätsmedizin	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Claudia Spies

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of postoperative delirium	Incidence of postoperative delirium measured with the Confusion Assessment Method for the ICU (CAM-ICU) or the Confusion Assessment Method (CAM)	Until the 5th postoperative day
Secondary	Incidence of subsyndromal delirium and severity of postoperative delirium	Incidence of Subsyndromal Delirium (SSD) and severity of postoperative Delirium measured with the Intensive Care Delirium Screening Checklist (ICDSC)	Until the 14th postoperative day/discharge
Secondary	Duration of delirium in the intensive care unit	Duration of intensive care unit-delirium measured with the Confusion Assessment Method for the ICU (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC)	Until the 14th postoperative day/discharge
Secondary	Severity of anxiety	Severity of anxiety measured with the Faces Anxiety Scale (FAS)	Up to three months
Secondary	Management of sedation	Management of sedation measured by the Richmond Agitation Sedation Scale (RASS)	Until the 5th postoperative day
Secondary	Management of vigilance	Management of Vigilance measured by Glasgow Coma Scale (GCS)	Until the 5th postoperative day
Secondary	Management of analgesia and pain levels	Management of analgesia and pain levels measured by Numeric Rating Scale - Visualized (NRS-V), the Faces Pain Scale - Revised (FPS-R), the Behavioral Pain Scale (BPS) or the Behavioral Pain Scale for Non-Intubated (BPS-NI)	Up to three months
Secondary	Relevant medication		Until the 5th postoperative day
Secondary	Severity of illness	Severity of illness measured by Sequential Organ Failure Assessment (SOFA-Score), Simplified Acute Physiology Score (SAPS II) and the Acute Physiology and Chronic Health Evaluation (APACHE II)	Up to 14 postoperative days
Secondary	Mechanical ventilation/weaning failure		Until the 5th postoperative day
Secondary	Intraoperative cerebral oxymetry		At time of surgery
Secondary	Processive Electroencephalography and Electromyography (EEG/EMG) -Data (SedLine®)		At time of surgery
Secondary	Determination of blood levels	Complete blood count performance (Sysmex®) and acetylcholinesterase-analysis	Change from baseline complete blood count performance (Sysmex®) and acetylcholinesterase-analysis at third postoperative day
Secondary	Cortisol-analysis		Up to three months
Secondary	Organ dysfunctions		Up to three months
Secondary	Infections	Infections according to surgical site infections (SSI) and according to the US Centers for Disease Control and Preventions (CDC).	Up to three months
Secondary	ICU length of stay		Participants will be followed for the duration of intensive care stay, an expected average of 2 days
Secondary	Hospital length of stay	Discharge criteria have to be met according to Post Anaesthetic Discharge Scoring System (PADSS) for monitoring patients discharge.	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks
Secondary	Quality of life	Quality of life is measured by EQ-5D (EuroQol Group), a measure generating a single index value for health status with considerable potential for use in health care evaluation	Up to three months
Secondary	Incidence of postoperative cognitive dysfunction	Incidence of postoperative cognitive dysfunction (POCD) is measured by Cambridge Neuropsychological Test Automated Battery (CANTAB®) and Mini Mental State Examination (MMSE) including subjective memory feeling (Item 10 of the Geriatric Depression Scale (for already included patients the retrospective follow up by telephone interview)), including limitations in daily activities (EQ-5D)	Up to three months
Secondary	Mortality		Up to three months
Secondary	Sleep quality		Up to three months
Secondary	Photomotor reflex		At time of surgery
Secondary	Changes of hemodynamic parameters in the intraoperative transesophageal echocardiography	Hemodynamic aparemters are measured in patients for elective CABG surgery	At time of surgery