Ignite Creation Date:
2025-12-24 @ 11:06 PM
Ignite Modification Date:
2026-02-23 @ 1:53 PM
Study NCT ID:
NCT04106869
Status:
WITHDRAWN
Last Update Posted:
2023-05-10
First Post:
2019-09-25
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
The Influence of Ventilation on Perioperative Neurocognitive Disorders
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D060825', 'term': 'Cognitive Dysfunction'}], 'ancestors': [{'id': 'D003072', 'term': 'Cognition Disorders'}, {'id': 'D019965', 'term': 'Neurocognitive Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR'], 'maskingDescription': "Patients will be blinded to the group, as well as the outcomes assessor and the investigator.\n\nThe anesthesiologist responsible for the patient's anesthesia will not be blinded."}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 0}}, 'statusModule': {'whyStopped': 'PI left the institution and the study was not continued', 'overallStatus': 'WITHDRAWN', 'startDateStruct': {'date': '2019-11-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-05', 'completionDateStruct': {'date': '2022-03-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2023-05-08', 'studyFirstSubmitDate': '2019-09-25', 'studyFirstSubmitQcDate': '2019-09-25', 'lastUpdatePostDateStruct': {'date': '2023-05-10', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2019-09-27', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-03-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'T-MOCA-baseline', 'timeFrame': '12 hours', 'description': 'In order to evaluate perioperative neurocognitive disorders, patients will take the T-MOCA test'}, {'measure': 'T-MOCA-6-weeks-postoperatively', 'timeFrame': '6 weeks', 'description': 'In order to evaluate perioperative neurocognitive disorders, patients will take the T-MOCA test'}, {'measure': 'T-MOCA-3-months-postoperatively', 'timeFrame': '3 months', 'description': 'In order to evaluate perioperative neurocognitive disorders, patients will take the T-MOCA test'}], 'secondaryOutcomes': [{'measure': "Concentration of patient's baseline pre-operative peripheral IL-6", 'timeFrame': '12 hours', 'description': 'Blood samples to measure IL-6 will be drawn prior to the surgery'}, {'measure': "Concentration of patient's post-operative peripheral IL-6; 6 hours post-operative", 'timeFrame': '24 hours', 'description': 'Blood samples to measure IL-6 will be drawn 6 hours after the surgery'}, {'measure': "Concentration of patient's post-operative peripheral IL-6 ; 24 hours post-operative", 'timeFrame': '24 hours', 'description': 'Blood samples to measure IL-6 will be drawn 24 hours after the surgery'}]}, 'oversightModule': {'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Cognitive Dysfunction']}, 'descriptionModule': {'briefSummary': 'This prospective study is designed to examine the influence of intra-operative ventilation on perioperative neurocognitive disorders in patients undergoing total hip arthroplasty.', 'detailedDescription': "Perioperative neurocognitive disorders (PND's) remain an important complication after surgery. After many years of speculating about the etiology of this complication, currently studies are pointing to an inflammatory cascade being set in motion. Following the combination of surgery/ anesthesia, high molecular group box protein 1 (HMGB1) is released. This damage-associated molecular pattern (DAMP) binds to pattern recognition receptors (PRR) on circulating bone marrow-derived monocytes (BM-DMs). Through an intracellular signaling pathway, the transcription factor NF-kappa B passes into the nucleus, is activated and increases expression and release of pro-inflammatory cytokines. These in turn disrupt the blood brain barrier. Within the brain parenchyma the chemokine monocyte chemoattractant protein 1 (MCP-1) is upregulated and attracts the BM-DMs through binding to its receptor, CCR2. In turn, this activates the resident quiescent microglia. Together, the BM-DMs and activated microglia release HMGB1 and pro-inflammatory cytokines that disrupt long-term potentiation (LTP) thereby blocking synaptic plasticity changes that are required for the cognitive functions of learning and memory.\n\nOptimizing intraoperative ventilation has been the goal of many studies, which have suggested obtaining protective ventilation through the use of low tidal volumes (6-8 ml/kg) and driving pressure below 15 mm Hg.\n\nVery few articles have focused on the influence of intra-operative ventilatory management on PND's.\n\nThis prospective study is designed to examine the influence of intra-operative ventilation on perioperative neurocognitive disorders in patients undergoing total hip arthroplasty.\n\nThe objectives in our study are to:\n\nEvaluate the influence of intra-operative ventilation on the incidence of incidence and duration of perioperative neurocognitive disorders in a known high-risk group of surgical patients.\n\nMeasure peripheral inflammatory markers (IL-6) in the same group of surgical patients.\n\nThe evaluation of the presence of peri-operative neurocognitive disorders in patients scheduled for a total hip arthroplasty will be done by using the T-MOCA test. Patients will have to take this test at three time-points (Baseline, 6 weeks post-operatively and 3 months post-operatively.) Patients will be randomized to two groups. One group will be ventilated to obtain intra-operative end-tidal CO2 below 35 mm Hg and the other group will be ventilated to obtain intra-operative end-tidal CO2 of 40-45 mm Hg. Peripheral inflammatory markers will as well be measured in the same group of patients.\n\nAnesthesia management of these patients will comply to our hospital's standard of care practice.\n\nMonitoring of Physiological Parameters During General Anesthesia: Heart rate, oxygen saturation (SpO2), respiratory rate, non-invasive blood pressure, end-tidal CO2 levels, inspired/end-tidal O2 levels, inspired/end-tidal sevoflurane concentrations, and temperature will be continuously monitored and recorded throughout the surgical procedure, to ensure that the measured physiological parameters are within the normal range.\n\nSimilarly, the cumulative doses of all sedative and analgesic medications will also be recorded.\n\nInduction and Maintenance of General Anesthesia:\n\nAll patients will receive general anesthesia using an endotracheal tube to facilitate ventilatory support.\n\nInduction of anesthesia will be performed using the following:\n\nI.V. Sufentanil 0.1- 0.2 mcg/kg I.V. Lidocaine 1.5 mg/kg I.V. Propofol 2-3 mg/kg I.V. Rocuronium 0.6 -1.2 mg/kg General anesthesia will be maintained using 0.5-2.5% sevoflurane in an O2:air mixture.\n\nVentilatory settings will be the following:\n\n6-8 ml/kg and Respiratory rate adjusted to the required ETC02 (end-tidal C02) PEEP (positive end-expiratory pressure) in order to ensure a driving pressure (P plateau- PEEP) below 15 mmHg Additional analgesia will be provided with I.V. Acetaminophen 15 mg/kg and I.V. Diclofenac 1 mg/kg, I.V. Tramadol 1-2 mg/kg and, if necessary, additional boluses of I.V. sufentanil 5 mcg.\n\nIf muscle relaxation is required by the surgeon, I.V. rocuronium may be administered in 10-20 mg boluses. I.V. Sugammadex 4 mg/kg will be administered if needed to reverse neuromuscular blockade.\n\nUpon emergence from anesthesia:\n\nAll patients will be transferred to the post-operative recovery unit."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['OLDER_ADULT'], 'maximumAge': '85 Years', 'minimumAge': '65 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Patients with an ASA (American Society of Anesthesia) score of I- III\n* Scheduled for total hip arthroplasty\n\nExclusion Criteria:\n\n* lack of local language comprehension\n* neuropsychiatric disturbance\n* history of drug/alcohol abuse\n* use of anticholinergic drugs, benzodiazepines, opiates/neuroleptic drugs\n* patients with an infectious disease within the last month/immune-suppressant therapy within the last 2 months (e.g., azathioprine or cyclosporine) or chronic medication with potential immune-modulatory effects\n* patients who underwent major surgery within the last 3 months\n* Patients with cardiovascular, or respiratory diseases (including smoking) resulting in clinically relevant impaired function\n* Patients with pre-existing CVA, dementia, and other neurological conditions that would interfere with their ability to participate cognitively\n* patients with active malignancy'}, 'identificationModule': {'nctId': 'NCT04106869', 'briefTitle': 'The Influence of Ventilation on Perioperative Neurocognitive Disorders', 'organization': {'class': 'OTHER', 'fullName': 'Université Libre de Bruxelles'}, 'officialTitle': 'Does Intra-operative Low End Tidal CO2 Aggravate Perioperative Neurocognitive Disorders?', 'orgStudyIdInfo': {'id': 'Venti-delirium'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Hyperventilation', 'description': 'Ventilatory settings will be the following:\n\n6-8 ml/kg and Respiratory rate adjusted to the required ETC02 (\\<35 mmHg) PEEP in order to ensure a driving pressure (P plateau- PEEP) below 15 mmHg.', 'interventionNames': ['Other: Hyperventilation']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Hypoventilation', 'description': 'Ventilatory settings will be the following:\n\n6-8 ml/kg and Respiratory rate adjusted to the required ETC02 ( 40-45 mmHg) PEEP in order to ensure a driving pressure (P plateau- PEEP) below 15 mmHg.', 'interventionNames': ['Other: Hypoventilation']}], 'interventions': [{'name': 'Hyperventilation', 'type': 'OTHER', 'description': 'Ventilatory settings will be the following:\n\n6-8 ml/kg and Respiratory rate adjusted to the required ETC02 (\\<35 mmHg) PEEP in order to ensure a driving pressure (P plateau- PEEP) below 15 mmHg.', 'armGroupLabels': ['Hyperventilation']}, {'name': 'Hypoventilation', 'type': 'OTHER', 'description': 'Ventilatory settings will be the following:\n\n6-8 ml/kg and Respiratory rate adjusted to the required ETC02 (40-45 mmHg) PEEP in order to ensure a driving pressure (P plateau- PEEP) below 15 mmHg.', 'armGroupLabels': ['Hypoventilation']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Charleroi', 'state': 'Hainaut', 'country': 'Belgium', 'facility': 'CHU-Charleroi Hopital Civil Marie Curie', 'geoPoint': {'lat': 50.41136, 'lon': 4.44448}}], 'overallOfficials': [{'name': 'Sarah Saxena, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'CHU Charleroi'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Université Libre de Bruxelles', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal Investigator', 'investigatorFullName': 'Sarah Saxena', 'investigatorAffiliation': 'Université Libre de Bruxelles'}}}}