Back to resultsNeuroprotection With Dexmedetomidine in Patients Undergoing Elective Cardiac or Abdominal Surgery (Neuprodex)
Primary Purpose
Delirium, Postoperative Cognitive Deficit (POCD)
Status
Completed
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
Dexmedetomidine (Dexdor®)
0.9% Sodium Chloride
Sponsored by
About this trial
This is an interventional treatment trial for Delirium focused on measuring Neuroprotection
Eligibility Criteria
Study Group:
Inclusion Criteria:
- Patients aged ≥ 60 years
- 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
- Offered patient information and written consent by the patient (according to German Drug Law § 40 (1) 3b)
- Premedication only with benzodiazepines
- Pain therapy during the operation with regional procedures and/or Sufentanil/Fentanyl
- Anesthesia in cardio surgery according to Heart-Lung-Apparatus
- Anesthesia with hypnotic agent Propofol
- Pain therapy after operation according to S3-Guideline
- Postoperative medication for anxiolysis only with benzodiazepines
Exclusion Criteria:
- Known drug intolerance/allergy: dexmedetomidine or to other ingredients
- Lacking willingness to save and hand out pseudonymised data within the clinical trial
- Accommodation in an institution due to an official or judicial order (according to AMG §40 (1) 4)
- Employee of the Charité - Universitätsmedizin Berlin CVK/CCM
- Illiteracy
- Inability to speak and/or read German
- Minimal mental status examination (MMSE) < 24
- Severe hearing loss or visual impairment
- Acute brain injury
- Intracranial haemorrhage within one year before participation in the study
- Manifest psychiatric disease
- Known illicit substance abuse
- Acute intoxication
- For women: Pregnancy or positive pregnancy test within the preoperative screening
- Homeless or other circumstances, where the patient would not be reachable by telephone or postal services for the 3-months follow up
- Participation in another interventional clinical trial according to the German Drug Law at time of inclusion and during the trial
- Acute circulatory failure at time of randomisation (severe hypotension with mean arterial pressure < 55 mmHg despite vasopressors or optimal preload)
- AV-conduction-block II or III (unless pacemaker installed)
- Severe bradycardia (heart-rate < 50 bpm, preoperative, permanent)
- Spinal cord injury with known autonomic dysregulation
- Preoperative acute cerebrovascular event with neurologic residues
- Liver insufficiency (Child C cirrhosis, MELD Score > 17)
- Application of Remifentanil during the operation
- Deep sedation (RASS, -4 to -5)
- Administration of Clonidine during administration of the study drug
- Additional administration of Dexmedetomidine within 3 months after study inclusion
Control Group:
Inclusion Criteria:
- Patients aged ≥ 60 years of European descent (Caucasian)
- Male or female patients with ASA II+III
- ASA II+III-patients, for which no operation is planned within the next year
- No operation in the last half year before study inclusion
- Offered patient information and written informed consent
Exclusion Criteria
- Minimal mental status examination (MMSE) < 24
- Missing informed consent for saving and hand out pseudonymous data
- Neuropsychiatric morbidity, which limits the conduction of the neurocognitive testing
- Anacusis or Hypoacusis, which limits the conduction of the neurocognitive testing
- Taking psychothropic drugs (including sleep-inducing drug and benzodiazepine) on a regular basis and other substances, which limit the conduction of the neurocognitive testing
Sites / Locations
- Department of Anesthesiology and Operative Intensive Care Medicine, Campus Charité Mitte and Campus Virchow - Klinikum, Charité- Universitätsmedizin
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Placebo Comparator
No Intervention
Arm Label
Study group
Control group
POCD control group
Arm Description
Application of Dexmedetomidine (Dexdor®) perioperatively for a maximum of 48 hours Dosing Scheme: during operation and mechanical ventilation: 0,7μg/kgABW/h; recovery time until extubation: 0,4μg/kgABW/h; after extubation: 0,2-1,4μg/kgABW/h
Application of placebo for a maximum of 48 hours
A non-surgical control group of 15 ASA II/III- patients is collected for measuring the learning experience during the cognitive testings. The participants are matched on age, education, and gender to the study patients.
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
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)
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)
Severity of anxiety
Severity of anxiety measured with the Faces Anxiety Scale (FAS)
Management of sedation
Management of sedation measured by the Richmond Agitation Sedation Scale (RASS)
Management of vigilance
Management of Vigilance measured by Glasgow Coma Scale (GCS)
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)
Relevant medication
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)
Mechanical ventilation/weaning failure
Intraoperative cerebral oxymetry
Processive Electroencephalography and Electromyography (EEG/EMG) -Data (SedLine®)
Determination of blood levels
Complete blood count performance (Sysmex®) and acetylcholinesterase-analysis
Cortisol-analysis
Organ dysfunctions
Infections
Infections according to surgical site infections (SSI) and according to the US Centers for Disease Control and Preventions (CDC).
ICU length of stay
Hospital length of stay
Discharge criteria have to be met according to Post Anaesthetic Discharge Scoring System (PADSS) for monitoring patients discharge.
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
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)
Mortality
Sleep quality
Photomotor reflex
Changes of hemodynamic parameters in the intraoperative transesophageal echocardiography
Hemodynamic aparemters are measured in patients for elective CABG surgery
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02096068
Brief Title
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
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
July 2014 (Actual)
Primary Completion Date
March 17, 2018 (Actual)
Study Completion Date
July 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Claudia Spies
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Delirium, Postoperative Cognitive Deficit (POCD)
Keywords
Neuroprotection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
78 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Study group
Arm Type
Experimental
Arm Description
Application of Dexmedetomidine (Dexdor®) perioperatively for a maximum of 48 hours
Dosing Scheme:
during operation and mechanical ventilation: 0,7μg/kgABW/h; recovery time until extubation: 0,4μg/kgABW/h; after extubation: 0,2-1,4μg/kgABW/h
Arm Title
Control group
Arm Type
Placebo Comparator
Arm Description
Application of placebo for a maximum of 48 hours
Arm Title
POCD control group
Arm Type
No Intervention
Arm Description
A non-surgical control group of 15 ASA II/III- patients is collected for measuring the learning experience during the cognitive testings. The participants are matched on age, education, and gender to the study patients.
Intervention Type
Drug
Intervention Name(s)
Dexmedetomidine (Dexdor®)
Intervention Description
Dexmedetomidine (Dexdor 100 micrograms/ml concentrate for solution for infusion)
Intervention Type
Drug
Intervention Name(s)
0.9% Sodium Chloride
Intervention Description
Solution for infusion: Sodium Chloride : 9.0 g/l; Each ml contains 9 mg sodium chloride mmol/l : Na+ : 154. Cl-: 154.
Primary Outcome Measure Information:
Title
Incidence of postoperative delirium
Description
Incidence of postoperative delirium measured with the Confusion Assessment Method for the ICU (CAM-ICU) or the Confusion Assessment Method (CAM)
Time Frame
Until the 5th postoperative day
Secondary Outcome Measure Information:
Title
Incidence of subsyndromal delirium and severity of postoperative delirium
Description
Incidence of Subsyndromal Delirium (SSD) and severity of postoperative Delirium measured with the Intensive Care Delirium Screening Checklist (ICDSC)
Time Frame
Until the 14th postoperative day/discharge
Title
Duration of delirium in the intensive care unit
Description
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)
Time Frame
Until the 14th postoperative day/discharge
Title
Severity of anxiety
Description
Severity of anxiety measured with the Faces Anxiety Scale (FAS)
Time Frame
Up to three months
Title
Management of sedation
Description
Management of sedation measured by the Richmond Agitation Sedation Scale (RASS)
Time Frame
Until the 5th postoperative day
Title
Management of vigilance
Description
Management of Vigilance measured by Glasgow Coma Scale (GCS)
Time Frame
Until the 5th postoperative day
Title
Management of analgesia and pain levels
Description
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)
Time Frame
Up to three months
Title
Relevant medication
Time Frame
Until the 5th postoperative day
Title
Severity of illness
Description
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)
Time Frame
Up to 14 postoperative days
Title
Mechanical ventilation/weaning failure
Time Frame
Until the 5th postoperative day
Title
Intraoperative cerebral oxymetry
Time Frame
At time of surgery
Title
Processive Electroencephalography and Electromyography (EEG/EMG) -Data (SedLine®)
Time Frame
At time of surgery
Title
Determination of blood levels
Description
Complete blood count performance (Sysmex®) and acetylcholinesterase-analysis
Time Frame
Change from baseline complete blood count performance (Sysmex®) and acetylcholinesterase-analysis at third postoperative day
Title
Cortisol-analysis
Time Frame
Up to three months
Title
Organ dysfunctions
Time Frame
Up to three months
Title
Infections
Description
Infections according to surgical site infections (SSI) and according to the US Centers for Disease Control and Preventions (CDC).
Time Frame
Up to three months
Title
ICU length of stay
Time Frame
Participants will be followed for the duration of intensive care stay, an expected average of 2 days
Title
Hospital length of stay
Description
Discharge criteria have to be met according to Post Anaesthetic Discharge Scoring System (PADSS) for monitoring patients discharge.
Time Frame
Participants will be followed for the duration of hospital stay, an expected average of 2 weeks
Title
Quality of life
Description
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
Time Frame
Up to three months
Title
Incidence of postoperative cognitive dysfunction
Description
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)
Time Frame
Up to three months
Title
Mortality
Time Frame
Up to three months
Title
Sleep quality
Time Frame
Up to three months
Title
Photomotor reflex
Time Frame
At time of surgery
Title
Changes of hemodynamic parameters in the intraoperative transesophageal echocardiography
Description
Hemodynamic aparemters are measured in patients for elective CABG surgery
Time Frame
At time of surgery
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Study Group:
Inclusion Criteria:
Patients aged ≥ 60 years
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
Offered patient information and written consent by the patient (according to German Drug Law § 40 (1) 3b)
Premedication only with benzodiazepines
Pain therapy during the operation with regional procedures and/or Sufentanil/Fentanyl
Anesthesia in cardio surgery according to Heart-Lung-Apparatus
Anesthesia with hypnotic agent Propofol
Pain therapy after operation according to S3-Guideline
Postoperative medication for anxiolysis only with benzodiazepines
Exclusion Criteria:
Known drug intolerance/allergy: dexmedetomidine or to other ingredients
Lacking willingness to save and hand out pseudonymised data within the clinical trial
Accommodation in an institution due to an official or judicial order (according to AMG §40 (1) 4)
Employee of the Charité - Universitätsmedizin Berlin CVK/CCM
Illiteracy
Inability to speak and/or read German
Minimal mental status examination (MMSE) < 24
Severe hearing loss or visual impairment
Acute brain injury
Intracranial haemorrhage within one year before participation in the study
Manifest psychiatric disease
Known illicit substance abuse
Acute intoxication
For women: Pregnancy or positive pregnancy test within the preoperative screening
Homeless or other circumstances, where the patient would not be reachable by telephone or postal services for the 3-months follow up
Participation in another interventional clinical trial according to the German Drug Law at time of inclusion and during the trial
Acute circulatory failure at time of randomisation (severe hypotension with mean arterial pressure < 55 mmHg despite vasopressors or optimal preload)
AV-conduction-block II or III (unless pacemaker installed)
Severe bradycardia (heart-rate < 50 bpm, preoperative, permanent)
Spinal cord injury with known autonomic dysregulation
Preoperative acute cerebrovascular event with neurologic residues
Liver insufficiency (Child C cirrhosis, MELD Score > 17)
Application of Remifentanil during the operation
Deep sedation (RASS, -4 to -5)
Administration of Clonidine during administration of the study drug
Additional administration of Dexmedetomidine within 3 months after study inclusion
Control Group:
Inclusion Criteria:
Patients aged ≥ 60 years of European descent (Caucasian)
Male or female patients with ASA II+III
ASA II+III-patients, for which no operation is planned within the next year
No operation in the last half year before study inclusion
Offered patient information and written informed consent
Exclusion Criteria
Minimal mental status examination (MMSE) < 24
Missing informed consent for saving and hand out pseudonymous data
Neuropsychiatric morbidity, which limits the conduction of the neurocognitive testing
Anacusis or Hypoacusis, which limits the conduction of the neurocognitive testing
Taking psychothropic drugs (including sleep-inducing drug and benzodiazepine) on a regular basis and other substances, which limit the conduction of the neurocognitive testing
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Claudia Spies, MD, Prof.
Organizational Affiliation
Charité-University Medicine (Berlin, Germany)
Official's Role
Study Director
Facility Information:
Facility Name
Department of Anesthesiology and Operative Intensive Care Medicine, Campus Charité Mitte and Campus Virchow - Klinikum, Charité- Universitätsmedizin
City
Berlin
ZIP/Postal Code
13353
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
35543164
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.
Results Reference
derived
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Neuroprotection With Dexmedetomidine in Patients Undergoing Elective Cardiac or Abdominal Surgery (Neuprodex)
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