Clinical trial NCT02096068: Neuroprotection With Dexmedetomidine in Patients Undergoing Elective Cardiac or Abdominal Surgery (Neuprodex)
Official title: Neuroprotection With Dexmedetomidine in Patients Undergoing Elective Cardiac or Abdominal Surgery (NEUPRODEX)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Delirium
Postoperative Cognitive Deficit (POCD)
Keywords: Neuroprotection
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2014-03-26
Enrollment: 78
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of postoperative delirium
timeFrame: Until the 5th postoperative day
Secondary outcomes:
measure: Incidence of subsyndromal delirium and severity of postoperative delirium
timeFrame: Until the 14th postoperative day/discharge
measure: Duration of delirium in the intensive care unit
timeFrame: Until the 14th postoperative day/discharge
measure: Severity of anxiety
timeFrame: Up to three months
measure: Management of sedation
timeFrame: Until the 5th postoperative day
measure: Management of vigilance
timeFrame: Until the 5th postoperative day
measure: Management of analgesia and pain levels
timeFrame: Up to three months
measure: Relevant medication
timeFrame: Until the 5th postoperative day
measure: Severity of illness
timeFrame: Up to 14 postoperative days
measure: Mechanical ventilation/weaning failure
timeFrame: Until the 5th postoperative day
measure: Intraoperative cerebral oxymetry
timeFrame: At time of surgery
measure: Processive Electroencephalography and Electromyography (EEG/EMG) -Data (SedLine®)
timeFrame: At time of surgery
measure: Determination of blood levels
timeFrame: Change from baseline complete blood count performance (Sysmex®) and acetylcholinesterase-analysis at third postoperative day
measure: Cortisol-analysis
timeFrame: Up to three months
measure: Organ dysfunctions
timeFrame: Up to three months
measure: Infections
timeFrame: Up to three months
measure: ICU length of stay
timeFrame: Participants will be followed for the duration of intensive care stay, an expected average of 2 days
measure: Hospital length of stay
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 2 weeks
measure: Quality of life
timeFrame: Up to three months
measure: Incidence of postoperative cognitive dysfunction
timeFrame: Up to three months
measure: Mortality
timeFrame: Up to three months
measure: Sleep quality
timeFrame: Up to three months
measure: Photomotor reflex
timeFrame: At time of surgery
measure: Changes of hemodynamic parameters in the intraoperative transesophageal echocardiography
timeFrame: At time of surgery
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Department of Anesthesiology and Operative Intensive Care Medicine, Campus Charité Mitte and Campus Virchow - Klinikum, Charité- Universitätsmedizin
Study officials:
affiliation: Charité-University Medicine (Berlin, Germany)
name: Claudia Spies, MD, Prof.
role: STUDY_DIRECTOR
References:
citation: Singh A, Brenna CTA, Broad J, Kaustov L, Choi S. The Effects of Dexmedetomidine on Perioperative Neurocognitive Outcomes After Cardiac Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Ann Surg. 2022 May 1;275(5):864-871. doi: 10.1097/SLA.0000000000005196. Epub 2021 Aug 27.