Biomarker Development for Postoperative Cognitive Impairment in the Elderly (BioCog)

Postoperative Cognitive Deficit (POCD) Clinical Trial

— BioCog  

Official title:

Biomarker Development for Postoperative Cognitive Impairment in the Elderly (BioCog)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02265263
• Other study ID #: BioCog
• Status: Terminated
• Start date: October 2014
• Est. completion date: June 2019

Study information

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

Clinical Trial Summary

The research leading consortium to these results has received funding from the European Union Seventh Framework Programme [FP7/2007-2013] under grant agreement no 602461 (www.biocog.eu).

The investigators will establish valid biomarkers panels (neuroimaging and molecular) for risk and clinical outcome prediction of postoperative delirium (POD)/postoperative cognitive deficit (POCD) in elective surgical patients (Age ≥ 65 years) in study centers in Berlin,Germany (data collection within 2 years after initial hospital stay) and Utrecht, The Netherlands (data collection within 1 year after initial hospital stay), thereof cerebrospinal fluid (only once on day of surgery in patients with planned spinal anesthesia/combined spinal epidural analgesia in patients, only in Berlin).

A control group of 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. The ASA II/III- control patients receive additionally MRI-scan (3 Tesla) at baseline, after 3 months and after 1 (Utrecht) and 2 years (Berlin).

To analyze scanner variability we additionally measure at maximum 20 subjects (Age ≥ 65 years, ASA I and II) from Utrecht in the MRI scanner (3-Tesla) in Berlin and vice versa.

A study group at maximum (n= 80) and is collected for measuring 7 Tesla MRI at two timepoints (Baseline and 90 days).The primary endponit of this substudy is gamma amino-butyric acid concentration in CNS after 3-months (measured by MRI). A retrospective comparison group (extracting 8000 intensive care unit patient data from the patient data management system during the BioCog study period in 2016) to analyse economic effects that are caused by the implementation of quality indicators in health care.

An interim-analysis is performed on the primary endpoint after 400 included patients.

The resulting (multivariate) expert system is expected: 1) to support clinical decision-making in patient care, e.g. to balance the individual POD/POCD risk against the expected overall clinical outcome of an (elective) surgical intervention, 2) to allow the design of more sophisticated and hypothesis-driven clinical studies and drug trials (translational research) in the future. The latter will be possible on the basis of biomarker-based sub-grouping of patients and a better understanding of relevant pathophysiological processes.

Furthermore, a state-of-the art clinical database and biobank will be created that does not yet exist worldwide. Both the expert system and the reference database/biobank will expand the leadership of the contributing academic institutions in this particular research area. In addition, the newly created biobank will become an integral part of the European Biobanking and Biomolecular Resources Research Infrastructure (BBMRI) which allows top address specific and hypothesis-driven research questions.

Most notably, the developed (multivariate) expert system also has the potential for commercialization. Possible customers are: 1) physicians and hospital departments being involved in pre-surgical decision making, 2) pharmaceutical industry intending to conduct biomarker-based drug trials in POD/POCD.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1054
• Est. completion date: June 2019
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Study Group (Berlin/Utrecht):

Inclusion Criteria:

• Male and female patients aged = 65 years, of European descent (Caucasian)

• Elective surgery with an expected operative time = 60 minutes

• Ability to give informed consent after receiving spoken and written information of the study

• Eligibility for magnetic resonance Imaging

Exclusion Criteria:

• Mini-Mental-State-Examination = 23 points

• Homelessness or other circumstances where the patient would not be reachable by phone or postal services during follow-up.

• Participation in another prospective interventional clinical study during participation in this clinical study during hospital stay

• Accommodation in an institution due to an official or judicial order

• 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

Intraoperative clectroencephalography - examinations (Study Group Berlin):

Exclusion criteria:

• Neurological preconditions

• Proposed neurological surgery

Control Group (Berlin/Utrecht):

Inclusion criteria:

• Male and female patients aged = 65 years, of European descent (Caucasian)

• ASA II and III patients

• No operation in the last half year before study inclusion

• Eligibility for magnetic resonance Imaging

Exclusion Criteria:

• Mini-Mental-State-Examination = 23 Points

• 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 substances, which limit the conduction of the neurocognitive testing

Control Group (Utrecht) - Scannervariability:

Inclusion criteria:

• Male and female patients aged = 65 years, of European descent (Caucasian)

• ASA I and II patients

• No operation in the last half year before study inclusion

• Eligibility for magnetic resonance Imaging

Study Group (Berlin) - 7 Tesla MRI:

Criteria as of the 3-Tesla- study group and additionally:

Exclusion criteria:

• absolute 7 - Tesla MRI-contraindications

• relative 7 - Tesla MRI-contraindications

Related Conditions & MeSH terms

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

Locations

Country	Name	City	State
Germany	Department of Anesthesiology and Intensive Care Medicine, CCM and CVK, Charité - Universitätsmedizin Berlin	Berlin
Netherlands	Department of Intensive Care Medicine, University Medical Center Utrecht	Utrecht

Sponsors (2)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	European Union

Countries where clinical trial is conducted

Germany,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Delirium	Postoperative delirium rate, defined according to Diagnostic and Statistical Manual of Mental Disorders (DSM-V) and/or as = 2 cumulative points in the nursing Delirium Screening Scale (Nu-DESC) and/or a positive Confusion Assessment Method (CAM) and/or Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) score and/or patient chart review that shows descriptions of delirium.	Participants will be followed for the duration of hospital stay, an expected average of 7 days
Primary	Incidence of postoperative cognitive deficit (POCD)	POCD will be measured by a defined Cambridge Neuropsychological Test Automated Battery (CANTAB) POCD will be measured by a defined Cambridge Neuropsychological Test Automated Battery (CANTAB) and paper pencil tests (TMT A und B, Grooved Pegboard) and the Mini - Mental State Examination (MMSE)	Up to 3 months after the operation
Secondary	Duration of Delirium	Diagnostic and Statistical Manual of Mental Disorders (DSM-V); Nursing Delirium Screening Scale (Nu-DESC); Intensive Care Delirium Screening Checklist (ICDSC); Delirium Detection Scale (DDS); Confusion Assessment Method for the Intensive Care Unit (CAM-ICU); Confusion Assessment Method (CAM); Chart Review	Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Secondary	Duration of subsyndromal postoperative delirium	Nu-DESC score 1 and/or any criteria suggestive of POD (as described under "Primary Outcome Measures") that do not fulfill DSM-5 criteria for delirium.	Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Secondary	Incidence of subsyndromal postoperative delirium	Nu-DESC score 1 and/or any criteria suggestive of POD (as described under "Primary Outcome Measures") that do not fulfill DSM-5 criteria for Delirium	Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Secondary	Intensive care unit length of stay		Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days
Secondary	Hospital length of stay		Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Secondary	Postoperative organ complications	Postoperative organ complications are classified according to Clavien - Dindo classification.	Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Secondary	Incidence of postoperative cognitive deficit	POCD will be measured by a defined Cambridge Neuropsychological Test Automated Battery (CANTAB), paper pencil tests (TMT A und B, Grooved Pegboard) and the Mini - Mental State Examination (MMSE)	1 year, 2 years, 5 years after the operation
Secondary	Socioeconomic characteristics	Study center Berlin: Health economic data according to cost of patient care (The §21 dataset (diagnoses and operation-codes). Hospital costs are calculated according to the Institute for the Hospital Remuneration System (InEK) calculation scheme to compare the refinanced costs in each cost category/cost-center segment from study center Charité. Necessity and indirect costs of medical care (outpatient visits) after hospital stay.	3 months, 1, 2 and 5 years after the operation
Secondary	Health related quality of life	Study center Berlin: Measurement by EQ-5D	3 months, 1, 2 and 5 years after the operation
Secondary	Barthel Index		3 months, 1, 2 and 5 years after the operation
Secondary	Instrumental activities of daily living scale		3 months, 1, 2 and 5 years after the operation
Secondary	Hand grip strength test		3 months, 1, 2 and 5 years after the operation
Secondary	Malnutrition	Mini Nutritional Assessment - Short form, Serum albumin	3 months, 1, 2 and 5 years after the operation
Secondary	Mobility	Timed up and go test	3 months, 1, 2 and 5 years after the operation
Secondary	Neuroimaging Biomarker		3 months, 1, 2 and 5 years after the operation
Secondary	Molecular Biomarker		3 months
Secondary	Health related Quality of life	Study center Utrecht: Measurement by EQ-5D	3 months, 1 year after the operation
Secondary	Socioeconomic characteristics	Study center Utrecht: Health economic data according to direct cost of patient care (inpatient and outpatient stays) and necessity and indirect costs of medical care (outpatient visits) after hospital stay.	3 months, 1 year after the operation
Secondary	Heart rate variability		Study center Berlin: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Secondary	Light Levels (lux)		Study center Berlin: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Secondary	Light frequencies		Study center Berlin: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Secondary	Depression	Hospital Anxiety and Depression Scale (HADS) (Study Center Utrecht), GDS-15 (Study Center Berlin)	Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Secondary	Anxiety	Faces Anxiety Scale (FAS)	Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Secondary	Electroencephalography (EEG)- Mapping	Study center Berlin: EEG with19 electrodes and hypo- and hyperventilation in physiological limits (no patients with neurological pre-existing conditions or proposed neuro-surgery)	At time of surgery
Secondary	Mortality		3 months, 1, 2 and 5 years after the operation
Secondary	Depth of consciousness index	Depth of consciousness index measured by processive Electroencephalography and Electromyography (EEG/EMG) -Data (SedLine®)	At time of surgery
Secondary	Intraoperative cerebral oxymetry		At time of surgery
Secondary	Changes of Electroencephalography	Signals are measured by EEG Monitor and Delir Monitor software	Participants will be followed up until the end of postanesthesia care unit, an exspected average of 2 days
Secondary	Depth of sedation	Intraoperatively: Observe´s Assessment of Alertness/Sedation scale (OAA/S) and postoperatievly: Richmond Agitation Sedation Scale (RASS)	At time of surgery and Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days
Secondary	Pain Scales	Perioperatively: Pain sensitivity questionnare; Pain Catastrophing Scale (PCS-GE)(PSQ); Numerische Rating Scale (NRS-V); Behavioural Pain Scale (BPS for ventilated) and BPS-NI (for non-ventilated) patients, Critical-Care Pain Observation Tool (CPOT); Rotterdam Elderly Pain Observation Scale (REPOS); Pupillometry by Neurolight; Intraoperatively: Measurement of the nociceptive flexion reflex threshold (Dolosys Paintracker); Measurement of the pupillary dilation reflex threshold (AlgiScan); Automatic collection of the data of the medication pumps; Multiple blood analysis to measure the plasma-concentrations of anesthetics; Automatic collection of the data of the SED-Line-EEG-Monitor.	3 months
Secondary	Quality indicators of intensive care unit	Study Center Berlin: This endpoint aims to analyse economic effects of the prospective study patients and retrospective control subjects in the intensive care unit that are caused by the implementation of quality indicators in health care.	Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days
Secondary	Glucosevariability	Measured by Continuous Glucose Monitoring System	At time of surgery and Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days
Secondary	Frailty		3 months, 1, 2 and 5 years after the operation
Secondary	Coagulationdisorder of the blood	Kidney marker	3 months

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