Postoperative Delirium (POD)BioCogNCT02265263
Biomarker Development for Postoperative Cognitive Impairment in the Elderly (BioCog)
An observational study of Postoperative Delirium (POD) and Postoperative Cognitive Deficit (POCD), run by Charite University, Berlin, Germany at 2 sites in 2 countries.
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). Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Postoperative Delirium (POD), Postoperative Cognitive Deficit (POCD)
- How many people
- 1,054 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Oct 2014to Jun 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Study population: Surgical patients, 65 years or above (Berlin/Utrecht) ASA I and II patients, 65 years or above (Utrecht) ASA II and III patients, 65 years or above (Berlin/Utrecht)
Who may be able to join
- 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
- Male and female patients aged ≥ 65 years, of European descent (Caucasian)
- ASA II and III patients
Show all 14Show fewer
- No operation in the last half year before study inclusion
- Eligibility for magnetic resonance Imaging
- 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:
Who cannot join
- 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
Show all 19Show fewer
- Anacusis or Hypoacusis, which limits the conduction of the neurocognitive testing
- Intraoperative clectroencephalography - examinations (Study Group Berlin):
- Neurological preconditions
- Proposed neurological surgery
- Control Group (Berlin/Utrecht):
- 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:
- absolute 7 - Tesla MRI-contraindications
- relative 7 - Tesla MRI-contraindications
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Germany1 site
Department of Anesthesiology and Intensive Care Medicine, CCM and CVK, Charité - Universitätsmedizin Berlin
Berlin, 13353
Netherlands1 site
Department of Intensive Care Medicine, University Medical Center Utrecht
Utrecht, 3584 CX
About this study
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).
Read more
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.
- Medical subject headings
- Emergence Delirium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Surgical patients - 3 Tesla MRI | A study group of at maximum n= 1200 is collected for measuring 3 Tesla MRI at two timepoints (Baseline and 90 days) in Berlin/Utrecht. They include surgical procedures within body cavity e.g. abdomen or thorax from departments of general surgery, urology, gynecology or thoracic surgery; orthopaedic operations (hip-, knee-, endoprosthesis or spine (including neurosurgical spine operations)); cardiac surgery and operation of extracranial/intracranial head and neck Data collection from study center Utrecht ist within one year after initial hospital stay. Data collection from study center Berlin is within two years after initial hospital stay. | |
| Patients ASA II/III - 3 Tesla MRI | A control group of at maximum n= 300 ASA II/III- patients is collected for measuring the learning experience during the cognitive testings. They are matched on age, education, and gender to the study patients. The 104 ASA II/III- patients should receive additionally MRI-scan (3 Tesla) at baseline, after 3 months and after 1 year in Utrecht, after 3 months, after 1, 2 years in Berlin. Data collection from study center Utrecht ist within one year after initial hospital stay. Data collection from study center Berlin is within five years after initial hospital stay. | |
| Volunteers ASA I/II - 3 Tesla MRI | To analyze scanner variability we additionally measure at maximum 20 subjects (Age ≥ 65 years) from Utrecht in the MRI scanner (3-Tesla) in Berlin and vice versa. | |
| Surgical patients - 7 Tesla MRI | A study Group of at maximum n= 80 should be collected for measuring 7 Tesla MRI at two timepoints (Baseline and 90 days) in Berlin. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Participants will be followed for the duration of hospital stay, an expected average of 7 days
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)
Measured: Up to 3 months after the operation
Secondary outcomes (34)
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
Measured: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
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.
Measured: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
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
Measured: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Intensive care unit length of stay
Measured: Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days
Hospital length of stay
Measured: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Postoperative organ complications
Postoperative organ complications are classified according to Clavien - Dindo classification.
Measured: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
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)
Measured: 1 year, 2 years, 5 years after the operation
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.
Measured: 3 months, 1, 2 and 5 years after the operation
Health related quality of life
Study center Berlin: Measurement by EQ-5D
Measured: 3 months, 1, 2 and 5 years after the operation
Barthel Index
Measured: 3 months, 1, 2 and 5 years after the operation
Instrumental activities of daily living scale
Measured: 3 months, 1, 2 and 5 years after the operation
Hand grip strength test
Measured: 3 months, 1, 2 and 5 years after the operation
Malnutrition
Mini Nutritional Assessment - Short form, Serum albumin
Measured: 3 months, 1, 2 and 5 years after the operation
Mobility
Timed up and go test
Measured: 3 months, 1, 2 and 5 years after the operation
Neuroimaging Biomarker
Measured: 3 months, 1, 2 and 5 years after the operation
Molecular Biomarker
Measured: 3 months
Health related Quality of life
Study center Utrecht: Measurement by EQ-5D
Measured: 3 months, 1 year after the operation
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.
Measured: 3 months, 1 year after the operation
Heart rate variability
Measured: Study center Berlin: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Light Levels (lux)
Measured: Study center Berlin: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Light frequencies
Measured: Study center Berlin: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Depression
Hospital Anxiety and Depression Scale (HADS) (Study Center Utrecht), GDS-15 (Study Center Berlin)
Measured: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Anxiety
Faces Anxiety Scale (FAS)
Measured: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
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)
Measured: At time of surgery
Mortality
Measured: 3 months, 1, 2 and 5 years after the operation
Depth of consciousness index
Depth of consciousness index measured by processive Electroencephalography and Electromyography (EEG/EMG) -Data (SedLine®)
Measured: At time of surgery
Intraoperative cerebral oxymetry
Measured: At time of surgery
Changes of Electroencephalography
Signals are measured by EEG Monitor and Delir Monitor software
Measured: Participants will be followed up until the end of postanesthesia care unit, an exspected average of 2 days
Depth of sedation
Intraoperatively: Observe´s Assessment of Alertness/Sedation scale (OAA/S) and postoperatievly: Richmond Agitation Sedation Scale (RASS)
Measured: At time of surgery and Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days
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.
Measured: 3 months
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.
Measured: Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days
Glucosevariability
Measured by Continuous Glucose Monitoring System
Measured: At time of surgery and Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days
Frailty
Measured: 3 months, 1, 2 and 5 years after the operation
Coagulationdisorder of the blood
Kidney marker
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2014 (estimated)
- Study startOct 2014
- Primary completionDec 2017
- Study completionJun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (31)Papers the sponsor has linked to this study.
- Other trials for Postoperative Delirium (POD)Studies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,054 participants (actual)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Collaborators
- European Union
- Responsible party
- Principal investigator, Claudia Spies, Charite University, Berlin, Germany
- Investigators
- Claudia Spies, MD Prof., Principal investigator, Department of Anesthesiology and Intensive Care Medicine, CVK/CCM, Charité - University Medicine BerlinGeorg Winterer (BioCog Research Program Coordinator), MD, PhD, Study chair, Department of Anesthesiology and Intensive Care Medicine, CVK/CCM, Charité - University Medicine Berlin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02265263
- Sponsor's protocol ID
- BioCog
- Acronym
- BioCog
- Status last verified
- Sep 2019
- First submitted
- 23 Sep 2014
- Last updated
- 25 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Fislage M, Feinkohl I, Lammers-Lietz F, Pischon T, Winterer G, Spies CD, Borchers F, Zacharias N; BioCog Consortium. Preoperative sodium abnormalities and adverse postoperative outcomes in older surgical patients: association and incremental predictive value in the BioCog cohort. Eur Geriatr Med. 2026 Sep 27. doi: 10.1007/s41999-026-01610-y. Online ahead of print.
PubMed 42802297Lammers-Lietz F, Akyuez L, Boraschi D, Borchers F, de Bresser J, Chatterjee S, Correia MM, de Lange NM, Dschietzig TB, Ghosh S, Feinkohl I, Ferreira da Silva I, Fislage M, Fournier A, Gallinat J, Hadzidiakos D, Hadel S, Halzl-Yurek F, Heilmann-Heimbach S, Heinrich M, Hendrikse J, Hoffmann P, Janke J, Kant IMJ, Kraft A, Krause R, Kruppa-Scheetz J, Kuhn S, Lachmann G, Laubach M, Lippert C, Menon DK, Morgeli R, Muller A, Mutsaerts HJ, Nothen M, Nurnberg P, Ofosu K, Pietzsch M, Piper SK, Pischon T, Preller J, Scheurer K, Schneider R, Scholtz K, Schreier PH, Slooter AJC, Stamatakis EA, von Haefen C, van Montfort SJT, van Dellen E, Volk HD, Weber S, Wiebach J, Wiehe A, Winterer JM, Wolf A, Zacharias N, Spies C, Winterer G; BioCog consortium. Prediction and risk evaluation of delirium after surgery in older patients: development and internal validation of an algorithm from the prospective BioCog cohort study. Br J Anaesth. 2026 May;136(5):1495-1508. doi: 10.1016/j.bja.2026.01.025. Epub 2026 Mar 17.
PubMed 41850989Van der A J, Lodema Y, Ten Bosch L, Van Heesch AB, Van Montfort SJT, Kant IMJ, Spies C, Van Dellen E, Slooter AJC. Quantitative Electroencephalogram Changes before and after Postoperative Delirium: A Prospective, Multicenter Cohort Study. Anesthesiology. 2026 Jun 1;144(6):1380-1390. doi: 10.1097/ALN.0000000000006026. Epub 2026 Mar 9.
PubMed 41805653Lammers-Lietz F, Borchers F, Feinkohl I, Kanar C, Krampe H, Lichtner G, Sreekanth J, Wiebach J, Weygandt M, Spies C, Winterer G, Paul F; BioCog consortium. Dopaminergic sub-network connectivity alterations are associated with postoperative cognitive dysfunction: Results from the observational BioCog cohort study. Eur J Anaesthesiol. 2026 Jul 1;43(7):603-614. doi: 10.1097/EJA.0000000000002365. Epub 2026 Feb 17.
PubMed 41699935Feinkohl I, Hadzidiakos D, Dschietzig TB, Janke J, Heinrich M, Slooter AJC, Spies C, Winterer G, Pischon T. Low-grade, systemic inflammation and the risk of perioperative neurocognitive disorders in an observational study of older adults. Sci Rep. 2025 Dec 20;15(1):44231. doi: 10.1038/s41598-025-31986-z.
PubMed 41419753Morgeli R, Borchers F, Feinkohl I, Piper SK, Pischon T, Slooter AJC, Spies C, Wiebach J, Winterer G, Zacharias N, Lammers-Lietz F. A secondary analysis of cortical atrophy and plasma amyloid beta patterns in older patients with cognitive frailty undergoing elective surgery. BMC Geriatr. 2025 Jul 2;25(1):484. doi: 10.1186/s12877-025-05740-z.
PubMed 40604523Starks SCE, Pohrt A, Halzl-Yurek F, Heinrich M, Muller A, Spies CD, Winterer G, Zacharias N. Long-term and pre-operative benzodiazepine use in older adults and risk for postoperative delirium: An additional analysis of the multicentre Biomarker Development for Postoperative Cognitive Impairment in the Elderly Study. Eur J Anaesthesiol. 2025 Aug 1;42(8):704-713. doi: 10.1097/EJA.0000000000002201. Epub 2025 May 16.
PubMed 40384317Feinkohl I, Janke J, Slooter AJC, Winterer G, Spies C, Pischon T. The Association of Plasma Leptin, Soluble Leptin Receptor and Total and High-Molecular Weight Adiponectin With the Risk of Perioperative Neurocognitive Disorders. Am J Geriatr Psychiatry. 2024 Sep;32(9):1119-1129. doi: 10.1016/j.jagp.2024.03.015. Epub 2024 Mar 30.
PubMed 38637191Heinrich M, Spies C, Borchers F, Feinkohl I, Pischon T, Slooter AJC, von Haefen C, Zacharias N, Winterer G, Lammers-Lietz F. Perioperative Levels of IL8 and IL18, but not IL6, are Associated with Nucleus Basalis Magnocellularis Atrophy Three Months after Surgery. J Neuroimmune Pharmacol. 2024 Mar 14;19(1):10. doi: 10.1007/s11481-024-10110-4.
PubMed 38483732Fislage M, Winzeck S, Woodrow R, Lammers-Lietz F, Stamatakis EA, Correia MM, Preller J, Feinkohl I, Hendrikse J, Pischon T, Spies CD, Slooter AJC, Winterer G, Menon DK, Zacharias N; BioCog Consortium. Structural disconnectivity in postoperative delirium: A perioperative two-center cohort study in older patients. Alzheimers Dement. 2024 Apr;20(4):2861-2872. doi: 10.1002/alz.13749. Epub 2024 Mar 7.
PubMed 38451782Trauzeddel RF, Rothe LM, Nordine M, Dehe L, Scholtz K, Spies C, Hadzidiakos D, Winterer G, Borchers F, Kruppa J, Treskatsch S. Influence of a chronic beta-blocker therapy on perioperative opioid consumption - a post hoc secondary analysis. BMC Anesthesiol. 2024 Feb 27;24(1):80. doi: 10.1186/s12871-024-02456-2.
PubMed 38413849Fislage M, Feinkohl I, Borchers F, Heinrich M, Pischon T, Veldhuijzen DS, Slooter AJC, Spies CD, Winterer G, Zacharias N; BioCog Consortium. Trail making test B in postoperative delirium: a replication study. BJA Open. 2023 Nov 3;8:100239. doi: 10.1016/j.bjao.2023.100239. eCollection 2023 Dec.
PubMed 37954892Fislage M, Feinkohl I, Borchers F, Pischon T, Spies CD, Winterer G, Zacharias N; BioCog Consortium. Preoperative thalamus volume is not associated with preoperative cognitive impairment (preCI) or postoperative cognitive dysfunction (POCD). Sci Rep. 2023 Jul 20;13(1):11732. doi: 10.1038/s41598-023-38673-x.
PubMed 37474784Feinkohl I, Janke J, Slooter AJC, Winterer G, Spies C, Pischon T; BioCog Consortium. Metabolic syndrome and the risk of postoperative delirium and postoperative cognitive dysfunction: a multi-centre cohort study. Br J Anaesth. 2023 Aug;131(2):338-347. doi: 10.1016/j.bja.2023.04.031. Epub 2023 Jun 20.
PubMed 37344340Ditzel FL, van Montfort SJT, Vernooij LM, Kant IMJ, Aarts E, Spies CD, Hendrikse J, Slooter AJC, van Dellen E; Biomarker Development for Postoperative Cognitive Impairment in the Elderly Consortium. Functional brain network and trail making test changes following major surgery and postoperative delirium: a prospective, multicentre, observational cohort study. Br J Anaesth. 2023 Feb;130(2):e281-e288. doi: 10.1016/j.bja.2022.07.054. Epub 2022 Oct 17.
PubMed 36261307
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarker Development for Postoperative Cognitive Impairment in the Elderly (BioCog)
- ClinicalTrials.gov ID
- NCT02265263
- Acronym / sponsor ID
- BioCog / BioCog
- Study type
- Observational
- Recruitment status
- Terminated
- Enrolment
- 1,054 participants (actual)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Collaborators
- European Union
- Study start
- Oct 2014 (actual)
- Primary completion
- Dec 2017 (actual)
- Study completion
- Jun 2019 (actual)
- First posted
- 15 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Surgical patients - 3 Tesla MRI | – | –A study group of at maximum n= 1200 is collected for measuring 3 Tesla MRI at two timepoints (Baseline and 90 days) in Berlin/Utrecht. They include surgical procedures within body cavity e.g. abdomen or thorax from departments of general surgery, urology, gynecology or thoracic surgery; orthopaedic operations (hip-, knee-, endoprosthesis or spine (including neurosurgical spine operations)); cardiac surgery and operation of extracranial/intracranial head and neck Data collection from study center Utrecht ist within one year after initial hospital stay. Data collection from study center Berlin is within two years after initial hospital stay. |
| Patients ASA II/III - 3 Tesla MRI | – | –A control group of at maximum n= 300 ASA II/III- patients is collected for measuring the learning experience during the cognitive testings. They are matched on age, education, and gender to the study patients. The 104 ASA II/III- patients should receive additionally MRI-scan (3 Tesla) at baseline, after 3 months and after 1 year in Utrecht, after 3 months, after 1, 2 years in Berlin. Data collection from study center Utrecht ist within one year after initial hospital stay. Data collection from study center Berlin is within five years after initial hospital stay. |
| Volunteers ASA I/II - 3 Tesla MRI | – | –To analyze scanner variability we additionally measure at maximum 20 subjects (Age ≥ 65 years) from Utrecht in the MRI scanner (3-Tesla) in Berlin and vice versa. |
| Surgical patients - 7 Tesla MRI | – | –A study Group of at maximum n= 80 should be collected for measuring 7 Tesla MRI at two timepoints (Baseline and 90 days) in Berlin. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
- Study population
- Surgical patients, 65 years or above (Berlin/Utrecht) ASA I and II patients, 65 years or above (Utrecht) ASA II and III patients, 65 years or above (Berlin/Utrecht)
Key inclusion criteria (14 listed)
- 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
- Male and female patients aged ≥ 65 years, of European descent (Caucasian)
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Incidence of Delirium
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 7 days
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.
Incidence of postoperative cognitive deficit (POCD)
Time frame: Up to 3 months after the operation
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)
34 secondary outcomes
Duration of Delirium
Time frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Duration of subsyndromal postoperative delirium
Time frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Incidence of subsyndromal postoperative delirium
Time frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Intensive care unit length of stay
Time frame: Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days
Hospital length of stay
Time frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Postoperative organ complications
Time frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Incidence of postoperative cognitive deficit
Time frame: 1 year, 2 years, 5 years after the operation
Socioeconomic characteristics
Time frame: 3 months, 1, 2 and 5 years after the operation
Health related quality of life
Time frame: 3 months, 1, 2 and 5 years after the operation
Barthel Index
Time frame: 3 months, 1, 2 and 5 years after the operation
Instrumental activities of daily living scale
Time frame: 3 months, 1, 2 and 5 years after the operation
Hand grip strength test
Time frame: 3 months, 1, 2 and 5 years after the operation
Malnutrition
Time frame: 3 months, 1, 2 and 5 years after the operation
Mobility
Time frame: 3 months, 1, 2 and 5 years after the operation
Neuroimaging Biomarker
Time frame: 3 months, 1, 2 and 5 years after the operation
Molecular Biomarker
Time frame: 3 months
Health related Quality of life
Time frame: 3 months, 1 year after the operation
Socioeconomic characteristics
Time frame: 3 months, 1 year after the operation
Heart rate variability
Time frame: Study center Berlin: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Light Levels (lux)
Time frame: Study center Berlin: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Light frequencies
Time frame: Study center Berlin: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Depression
Time frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Anxiety
Time frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Electroencephalography (EEG)- Mapping
Time frame: At time of surgery
Mortality
Time frame: 3 months, 1, 2 and 5 years after the operation
Depth of consciousness index
Time frame: At time of surgery
Intraoperative cerebral oxymetry
Time frame: At time of surgery
Changes of Electroencephalography
Time frame: Participants will be followed up until the end of postanesthesia care unit, an exspected average of 2 days
Depth of sedation
Time frame: At time of surgery and Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days
Pain Scales
Time frame: 3 months
Quality indicators of intensive care unit
Time frame: Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days
Glucosevariability
Time frame: At time of surgery and Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days
Frailty
Time frame: 3 months, 1, 2 and 5 years after the operation
Coagulationdisorder of the blood
Time frame: 3 months
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2019.
- Derived from this study: PubMed 42802297Fislage M, Feinkohl I, Lammers-Lietz F, Pischon T, Winterer G, Spies CD, Borchers F, Zacharias N; BioCog Consortium. Preoperative sodium abnormalities and adverse postoperative outcomes in older surgical patients: association and incremental predictive value in the BioCog cohort. Eur Geriatr Med. 2026 Sep 27. doi: 10.1007/s41999-026-01610-y. Online ahead of print.
- Derived from this study: PubMed 41850989Lammers-Lietz F, Akyuez L, Boraschi D, Borchers F, de Bresser J, Chatterjee S, Correia MM, de Lange NM, Dschietzig TB, Ghosh S, Feinkohl I, Ferreira da Silva I, Fislage M, Fournier A, Gallinat J, Hadzidiakos D, Hadel S, Halzl-Yurek F, Heilmann-Heimbach S, Heinrich M, Hendrikse J, Hoffmann P, Janke J, Kant IMJ, Kraft A, Krause R, Kruppa-Scheetz J, Kuhn S, Lachmann G, Laubach M, Lippert C, Menon DK, Morgeli R, Muller A, Mutsaerts HJ, Nothen M, Nurnberg P, Ofosu K, Pietzsch M, Piper SK, Pischon T, Preller J, Scheurer K, Schneider R, Scholtz K, Schreier PH, Slooter AJC, Stamatakis EA, von Haefen C, van Montfort SJT, van Dellen E, Volk HD, Weber S, Wiebach J, Wiehe A, Winterer JM, Wolf A, Zacharias N, Spies C, Winterer G; BioCog consortium. Prediction and risk evaluation of delirium after surgery in older patients: development and internal validation of an algorithm from the prospective BioCog cohort study. Br J Anaesth. 2026 May;136(5):1495-1508. doi: 10.1016/j.bja.2026.01.025. Epub 2026 Mar 17.
- Derived from this study: PubMed 41805653Van der A J, Lodema Y, Ten Bosch L, Van Heesch AB, Van Montfort SJT, Kant IMJ, Spies C, Van Dellen E, Slooter AJC. Quantitative Electroencephalogram Changes before and after Postoperative Delirium: A Prospective, Multicenter Cohort Study. Anesthesiology. 2026 Jun 1;144(6):1380-1390. doi: 10.1097/ALN.0000000000006026. Epub 2026 Mar 9.
- Derived from this study: PubMed 41699935Lammers-Lietz F, Borchers F, Feinkohl I, Kanar C, Krampe H, Lichtner G, Sreekanth J, Wiebach J, Weygandt M, Spies C, Winterer G, Paul F; BioCog consortium. Dopaminergic sub-network connectivity alterations are associated with postoperative cognitive dysfunction: Results from the observational BioCog cohort study. Eur J Anaesthesiol. 2026 Jul 1;43(7):603-614. doi: 10.1097/EJA.0000000000002365. Epub 2026 Feb 17.
- Derived from this study: PubMed 41419753Feinkohl I, Hadzidiakos D, Dschietzig TB, Janke J, Heinrich M, Slooter AJC, Spies C, Winterer G, Pischon T. Low-grade, systemic inflammation and the risk of perioperative neurocognitive disorders in an observational study of older adults. Sci Rep. 2025 Dec 20;15(1):44231. doi: 10.1038/s41598-025-31986-z.
- Derived from this study: PubMed 40604523Morgeli R, Borchers F, Feinkohl I, Piper SK, Pischon T, Slooter AJC, Spies C, Wiebach J, Winterer G, Zacharias N, Lammers-Lietz F. A secondary analysis of cortical atrophy and plasma amyloid beta patterns in older patients with cognitive frailty undergoing elective surgery. BMC Geriatr. 2025 Jul 2;25(1):484. doi: 10.1186/s12877-025-05740-z.
- Derived from this study: PubMed 40384317Starks SCE, Pohrt A, Halzl-Yurek F, Heinrich M, Muller A, Spies CD, Winterer G, Zacharias N. Long-term and pre-operative benzodiazepine use in older adults and risk for postoperative delirium: An additional analysis of the multicentre Biomarker Development for Postoperative Cognitive Impairment in the Elderly Study. Eur J Anaesthesiol. 2025 Aug 1;42(8):704-713. doi: 10.1097/EJA.0000000000002201. Epub 2025 May 16.
- Derived from this study: PubMed 38637191Feinkohl I, Janke J, Slooter AJC, Winterer G, Spies C, Pischon T. The Association of Plasma Leptin, Soluble Leptin Receptor and Total and High-Molecular Weight Adiponectin With the Risk of Perioperative Neurocognitive Disorders. Am J Geriatr Psychiatry. 2024 Sep;32(9):1119-1129. doi: 10.1016/j.jagp.2024.03.015. Epub 2024 Mar 30.
- Derived from this study: PubMed 38483732Heinrich M, Spies C, Borchers F, Feinkohl I, Pischon T, Slooter AJC, von Haefen C, Zacharias N, Winterer G, Lammers-Lietz F. Perioperative Levels of IL8 and IL18, but not IL6, are Associated with Nucleus Basalis Magnocellularis Atrophy Three Months after Surgery. J Neuroimmune Pharmacol. 2024 Mar 14;19(1):10. doi: 10.1007/s11481-024-10110-4.
- Derived from this study: PubMed 38451782Fislage M, Winzeck S, Woodrow R, Lammers-Lietz F, Stamatakis EA, Correia MM, Preller J, Feinkohl I, Hendrikse J, Pischon T, Spies CD, Slooter AJC, Winterer G, Menon DK, Zacharias N; BioCog Consortium. Structural disconnectivity in postoperative delirium: A perioperative two-center cohort study in older patients. Alzheimers Dement. 2024 Apr;20(4):2861-2872. doi: 10.1002/alz.13749. Epub 2024 Mar 7.
- Derived from this study: PubMed 38413849Trauzeddel RF, Rothe LM, Nordine M, Dehe L, Scholtz K, Spies C, Hadzidiakos D, Winterer G, Borchers F, Kruppa J, Treskatsch S. Influence of a chronic beta-blocker therapy on perioperative opioid consumption - a post hoc secondary analysis. BMC Anesthesiol. 2024 Feb 27;24(1):80. doi: 10.1186/s12871-024-02456-2.
- Derived from this study: PubMed 37954892Fislage M, Feinkohl I, Borchers F, Heinrich M, Pischon T, Veldhuijzen DS, Slooter AJC, Spies CD, Winterer G, Zacharias N; BioCog Consortium. Trail making test B in postoperative delirium: a replication study. BJA Open. 2023 Nov 3;8:100239. doi: 10.1016/j.bjao.2023.100239. eCollection 2023 Dec.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Claudia Spies, MD Prof. principal investigator
Department of Anesthesiology and Intensive Care Medicine, CVK/CCM, Charité - University Medicine Berlin
Georg Winterer (BioCog Research Program Coordinator), MD, PhD study chair
Department of Anesthesiology and Intensive Care Medicine, CVK/CCM, Charité - University Medicine Berlin
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Postoperative Delirium (POD) and Postoperative Cognitive Deficit (POCD), run by Charite University, Berlin, Germany at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Delirium (time frame: Participants will be followed for the duration of hospital stay, an expected average of 7 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02265263, which also lists 31 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2019.