Ignite Creation Date:
2025-12-24 @ 3:56 PM
Ignite Modification Date:
2025-12-24 @ 3:56 PM
Study NCT ID:
NCT06859892
Status:
RECRUITING
Last Update Posted:
2025-03-19
First Post:
2025-02-28
Is Possible Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Dexmedetomidine-Esketamine Combination and Sleep Disturbances After Major Noncardiac Surgery
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 476}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2025-03-18', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-03', 'completionDateStruct': {'date': '2026-12', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-03-18', 'studyFirstSubmitDate': '2025-02-28', 'studyFirstSubmitQcDate': '2025-02-28', 'lastUpdatePostDateStruct': {'date': '2025-03-19', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2025-03-05', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-11', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Time to extubation after surgery', 'timeFrame': 'On the day of surgery', 'description': 'Time interval from end of surgery to extubation.'}, {'measure': 'Incidence of emergence agitation after surgery', 'timeFrame': 'Up to 2 hours after extubation', 'description': 'Emergence agitation was defined as a Richmond Agitation-Sedation Scale (RASS) score ≥ +2 at any time point from tracheal extubation to discharge from the post-anesthesia care unit (PACU)'}, {'measure': 'Cumulative opioid consumption within 48 hours after surgery', 'timeFrame': 'Within 48 hours after surgery', 'description': 'Cumulative opioid consumption from end of surgery to 48 hours after surgery.'}, {'measure': 'Proportion of patients requiring rescue analgesia within 48 hours after surgery', 'timeFrame': 'Within 48 hours after surgery', 'description': 'Rescue analgesia indicates any analgesics in addition to patient-controlled intravenous analgesia.'}, {'measure': 'Length of hospital stay after surgery', 'timeFrame': 'Up to 30 days after surgery.', 'description': 'Time interval from end of surgery to hospital discharge.'}, {'measure': 'Agitation and sedation levels during the first 3 postoperative days', 'timeFrame': 'Up to 3 days after surgery', 'description': 'Agitation and sedation levels are assessed using the Richmond Agitation-Sedation Scale (RASS) twice daily (8:00 am to 10:00 am, and 18:00 pm -20:00) during the first 3 postoperative days.'}, {'measure': 'Incidence of postoperative complications', 'timeFrame': 'Up to 30 days after surgery', 'description': 'Postoperative complications are defined as new onset conditions that are deemed harmful and and require therapeutic intervention, i.e., class II or above on the Clavien-Dindo classification.'}, {'measure': 'All-cause 30-day mortality', 'timeFrame': 'Up to 30 days after surgery', 'description': 'All-cause death within 30 days after surgery.'}], 'primaryOutcomes': [{'measure': 'Incidence of sleep disturbances within 3 days after surgery', 'timeFrame': 'Up to 3 days after surgery', 'description': 'Sleep disturbances are defined as Richards-Campbell Sleep Questionnaire (RCSQ) score below 50, based on assessments conducted daily between 8:00 am and 10:00 am during postoperative days 1 to 3.'}], 'secondaryOutcomes': [{'measure': 'Quality of recovery at 24 hours after surgery', 'timeFrame': 'At 24 hours after surgery', 'description': 'Quality of recovery is assessed using the Quality of Recovery-15 (QoR-15) scale at 24 hours after surgery. The total QoR-15 scores are evaluated based on physical comfort (five items), emotional state (four items), psychological support (two items), physical independence (two items), and pain (two items) for QoR-15 questionnaire. Each item is scored from 0 to 10, and the possible total score ranges from 0 to 150, with higher scores representing better recovery quality after operation.'}, {'measure': 'Subjective sleep quality in the first 3 nights after surgery.', 'timeFrame': 'Up to 3 days after surgery.', 'description': 'Subjective sleep quality is assessed daily (8:00 am to 10:00 am) using the Richards-Campbell Sleep Questionnaire (RCSQ) during the first 3 postoperative days. Richards-Campbell Sleep Questionnaire (RCSQ) comprises five items: sleep depth, sleep latency, awakenings, returning to sleep, and sleep quality. Each item is assessed with a 100-mm visual analog scale. The scores range from 0, indicating the worst possible sleep, to 100, indicating the best possible sleep. The total RCSQ sleep score is derived by summing up the individual scores on the five sleep items and dividing it by 5.'}, {'measure': 'Pain intensity both at rest and with movement during the first 3 postoperative days', 'timeFrame': 'Up to 3 days after surgery', 'description': 'Pain intensity is assessed with the numeric rating scale (NRS; an 11-point scale where 0=no pain and 10=the worst pain) twice daily (8:00 am to 10:00 am, and 18:00 pm to 20:00 pm) both at rest and with movement during the first 3 postoperative days.'}, {'measure': 'Anxiety and depression on the third day after surgery', 'timeFrame': 'On the third day after surgery', 'description': 'Postoperative anxiety and depression are assessed using the Hospital Anxiety and Depression Scale (HADS), with scores categorized as follows: 0-7 (negative), 8-10 (mild), 11-14 (moderate), and 15-21 (severe).'}, {'measure': 'Subjective sleep quality on the 30th day after surgery', 'timeFrame': 'On the 30th day after surgery', 'description': 'Subjective sleep quality is assessed with the Pittsburgh Sleep Quality Index (PSQI) on the 30th postoperative day.'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['adults', 'major noncardiac surgery', 'dexmedetomidine', 'esketamine', 'postoperative sleep disturbances'], 'conditions': ['Adults', 'Major Noncardiac Surgery', 'Dexmedetomidine', 'Esketamine', 'Postoperative Sleep Disturbances']}, 'referencesModule': {'references': [{'pmid': '33675989', 'type': 'BACKGROUND', 'citation': 'Allen RW, Burney CP, Davis A, Henkin J, Kelly J, Judd BG, Ivatury SJ. Deep Sleep and Beeps: Sleep Quality Improvement Project in General Surgery Patients. J Am Coll Surg. 2021 Jun;232(6):882-888. doi: 10.1016/j.jamcollsurg.2021.02.010. Epub 2021 Mar 3.'}, {'pmid': '35430086', 'type': 'BACKGROUND', 'citation': 'Myles PS, Shulman MA, Reilly J, Kasza J, Romero L. Measurement of quality of recovery after surgery using the 15-item quality of recovery scale: a systematic review and meta-analysis. Br J Anaesth. 2022 Jun;128(6):1029-1039. doi: 10.1016/j.bja.2022.03.009. Epub 2022 Apr 14.'}, {'pmid': '22893770', 'type': 'BACKGROUND', 'citation': 'Kjolhede P, Langstrom P, Nilsson P, Wodlin NB, Nilsson L. The impact of quality of sleep on recovery from fast-track abdominal hysterectomy. J Clin Sleep Med. 2012 Aug 15;8(4):395-402. doi: 10.5664/jcsm.2032.'}, {'pmid': '32007403', 'type': 'BACKGROUND', 'citation': 'Gulam S, Xyrichis A, Lee GA. Still too noisy - An audit of sleep quality in trauma and orthopaedic patients. Int Emerg Nurs. 2020 Mar;49:100812. doi: 10.1016/j.ienj.2019.100812. Epub 2020 Jan 30.'}, {'pmid': '28069386', 'type': 'BACKGROUND', 'citation': 'Ruiz FS, Andersen ML, Guindalini C, Araujo LP, Lopes JD, Tufik S. Sleep influences the immune response and the rejection process alters sleep pattern: Evidence from a skin allograft model in mice. Brain Behav Immun. 2017 Mar;61:274-288. doi: 10.1016/j.bbi.2016.12.027. Epub 2017 Jan 7.'}, {'pmid': '24074687', 'type': 'BACKGROUND', 'citation': 'Chouchou F, Khoury S, Chauny JM, Denis R, Lavigne GJ. Postoperative sleep disruptions: a potential catalyst of acute pain? Sleep Med Rev. 2014 Jun;18(3):273-82. doi: 10.1016/j.smrv.2013.07.002. Epub 2013 Sep 24.'}, {'pmid': '24140074', 'type': 'BACKGROUND', 'citation': 'Fernandes NM, Nield LE, Popel N, Cantor WJ, Plante S, Goldman L, Prabhakar M, Manlhiot C, McCrindle BW, Miner SE. Symptoms of disturbed sleep predict major adverse cardiac events after percutaneous coronary intervention. Can J Cardiol. 2014 Jan;30(1):118-24. doi: 10.1016/j.cjca.2013.07.009. Epub 2013 Oct 16.'}, {'pmid': '31505369', 'type': 'BACKGROUND', 'citation': 'Lu Y, Li YW, Wang L, Lydic R, Baghdoyan HA, Shi XY, Zhang H. Promoting sleep and circadian health may prevent postoperative delirium: A systematic review and meta-analysis of randomized clinical trials. Sleep Med Rev. 2019 Dec;48:101207. doi: 10.1016/j.smrv.2019.08.001. Epub 2019 Aug 22.'}, {'pmid': '34393534', 'type': 'BACKGROUND', 'citation': 'Wang X, Hua D, Tang X, Li S, Sun R, Xie Z, Zhou Z, Zhao Y, Wang J, Li S, Luo A. The Role of Perioperative Sleep Disturbance in Postoperative Neurocognitive Disorders. Nat Sci Sleep. 2021 Aug 6;13:1395-1410. doi: 10.2147/NSS.S320745. eCollection 2021.'}, {'pmid': '39108199', 'type': 'BACKGROUND', 'citation': 'Meewisse AJG, Gribnau A, Thiessen SE, Stenvers DJ, Hermanides J, van Zuylen ML. Effect of time of day on outcomes in elective surgery: a systematic review. Anaesthesia. 2024 Dec;79(12):1325-1334. doi: 10.1111/anae.16395. Epub 2024 Aug 7.'}, {'pmid': '32765143', 'type': 'BACKGROUND', 'citation': 'Song B, Li Y, Teng X, Li X, Yang Y, Zhu J. Comparison of Morning and Evening Operation Under General Anesthesia on Intraoperative Anesthetic Requirement, Postoperative Sleep Quality, and Pain: A Randomized Controlled Trial. Nat Sci Sleep. 2020 Jul 16;12:467-475. doi: 10.2147/NSS.S257896. eCollection 2020.'}, {'pmid': '32733363', 'type': 'BACKGROUND', 'citation': 'Luo M, Song B, Zhu J. Sleep Disturbances After General Anesthesia: Current Perspectives. Front Neurol. 2020 Jul 8;11:629. doi: 10.3389/fneur.2020.00629. eCollection 2020.'}, {'pmid': '24158050', 'type': 'BACKGROUND', 'citation': 'Chung F, Liao P, Elsaid H, Shapiro CM, Kang W. Factors associated with postoperative exacerbation of sleep-disordered breathing. Anesthesiology. 2014 Feb;120(2):299-311. doi: 10.1097/ALN.0000000000000041.'}, {'pmid': '32210652', 'type': 'BACKGROUND', 'citation': 'Duan G, Wang K, Peng T, Wu Z, Li H. The Effects of Intraoperative Dexmedetomidine Use and Its Different Dose on Postoperative Sleep Disturbance in Patients Who Have Undergone Non-Cardiac Major Surgery: A Real-World Cohort Study. Nat Sci Sleep. 2020 Mar 12;12:209-219. doi: 10.2147/NSS.S239706. eCollection 2020.'}, {'pmid': '29120927', 'type': 'BACKGROUND', 'citation': 'Su X, Wang DX. Improve postoperative sleep: what can we do? Curr Opin Anaesthesiol. 2018 Feb;31(1):83-88. doi: 10.1097/ACO.0000000000000538.'}, {'pmid': '22831887', 'type': 'BACKGROUND', 'citation': 'Krenk L, Jennum P, Kehlet H. Sleep disturbances after fast-track hip and knee arthroplasty. Br J Anaesth. 2012 Nov;109(5):769-75. doi: 10.1093/bja/aes252. Epub 2012 Jul 24.'}, {'pmid': '18037670', 'type': 'BACKGROUND', 'citation': 'Gogenur I, Wildschiotz G, Rosenberg J. Circadian distribution of sleep phases after major abdominal surgery. Br J Anaesth. 2008 Jan;100(1):45-9. doi: 10.1093/bja/aem340. Epub 2007 Nov 23.'}]}, 'descriptionModule': {'briefSummary': 'Sleep disturbances are common early after major surgery, and are associated with delayed recovery. A previous study showed that dexmedetomidine-esketamine combination as a supplement to patient-controlled intravenous analgesia improved postoperative analgesia and subjective sleep quality in patients after scoliosis correction surgery. The purpose of this trial is to test the hypothesis that dexmedetomidine-esketamine combination used as a supplement during general anesthesia and postoperative intravenous analgesia may reduce sleep disturbances in adult after major noncardiac surgery.', 'detailedDescription': 'Sleep disturbances after surgery is usually manifested as sleep deprivation, altered circadian rhythm, and disturbed sleep structure. The reported incidence of sleep disturbances was 31.4% after gynecologic surgery, 31.9% after urologic surgery, and 35.9% after spine surgery. The occurrence of sleep disturbances is associated with worse perioperative outcomes, including aggravated pain intensity, increased delirium, higher risk of cardiovascular events, and delayed hospital discharge.\n\nDexmedetomidine is a high-specific alpha 2-adrenergic agonist with anxiolytic, sedative, and analgesic effects. When used during general anesthesia and for postoperative analgesia, dexmedetomidine is associated with improved analgesia and sleep quality. The effect of dexmedetomidine is dose-dependent. However, even commonly used dosage increases bradycardia and hypotension.\n\nKetamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. Esketamine is the S-enantiomer of racemic ketamine with a higher affinity for NMDA receptors and is approximately twice as potent as racemic ketamine in analgesia. When used during general anesthesia and for postoperative analgesia, esketamine improves analgesia and reduces opioid consumption, but psychiatric symptoms may occur.\n\nThe sedative effect of dexmedetomidine is helpful to relieve psychiatric side effects of ketamine/esketamine. A previous study showed that dexmedetomidine-esketamine combination as a supplement to patient-controlled intravenous analgesia improved postoperative analgesia and subjective sleep quality in patients after scoliosis correction surgery.\n\nThis trial is designed to test the hypothesis that dexmedetomidine-esketamine combination used as a supplement during general anesthesia and postoperative intravenous analgesia may reduce sleep disturbances in adult after major noncardiac surgery.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n1. Aged ≥18 years.\n2. Scheduled for major noncardiac surgery (≥60 minutes) under general anesthesia with an expected end of surgery no later than 18:00 pm.\n3. Required patient-controlled intravenous analgesia after surgery.\n\nExclusion Criteria:\n\n1. Emergency surgery, transurethral surgery, organ transplantation.\n2. Pregnant or lactating women.\n3. Patients who need hypnotics for sleep disturbance or antidepressants for depression prior to surgery.\n4. History of schizophrenia, epilepsy, Parkinson's disease, or myasthenia gravis.\n5. Inability to communicate due to coma, severe dementia, or speech disorders, endured hypoxic encephalopathy or traumatic brain injury, or after neurosurgery.\n6. Comorbid with hyperthyroidism and pheochromocytoma.\n7. Preoperative left ventricular ejection fraction \\<30%, sick sinus syndrome, severe sinus bradycardia (heart rate \\<50 beats/min), atrioventricular block of degree II or higher without pacemaker implantation, or systolic blood pressure below 90 mmHg despite use of vasopressors.\n8. Diagnosed as sleep apnea, or judged to be at high risk of moderate-to-severe sleep apnea as assessed by STOP-Bang.\n9. Severe hepatic dysfunction (Child-Pugh class C), severe renal dysfunction (on dialysis), or ASA classification ≥IV.\n10. Hypersensitive to dexmedetomidine and/or esketamine.\n11. Other conditions that are deemed unsuitable for study participation."}, 'identificationModule': {'nctId': 'NCT06859892', 'briefTitle': 'Dexmedetomidine-Esketamine Combination and Sleep Disturbances After Major Noncardiac Surgery', 'organization': {'class': 'OTHER', 'fullName': 'Peking University First Hospital'}, 'officialTitle': 'Effect of Dexmedetomidine-esketamine Combination on Sleep Disturbances After Major Noncardiac Surgery: a Single-center, Randomised, Double-blind, Placebo-controlled Trial', 'orgStudyIdInfo': {'id': '2024-729'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Dexmedetomidine-esketamine group', 'description': 'Dexmedetomidine-esketamine combination is infused during general anesthesia and used as a supplement for patient-controlled intravenous analgesia after surgery.', 'interventionNames': ['Drug: Dexmedetomidine-esketamine combination']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo group', 'description': 'Placebo (normal saline) is infused during general anesthesia and used as a supplement for patient-controlled intravenous analgesia after surgery.', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Dexmedetomidine-esketamine combination', 'type': 'DRUG', 'description': 'Dexmedetomidine 0.4 μg/kg and esketamine 0.2 mg/kg is infused over 10 minutes before anesthesia induction. Dexmedetomidine 0.20 μg/kg/h and esketamine 0.10 mg/kg/h is then infused until 60 minutes before the expected end of surgery. Patient-controlled intravenous analgesia is established with 100 μg dexmedetomidine, 50 mg esketamine, and 100 μg sufentanil, diluted to 100 mL with normal saline, and programmed to deliver 2-mL boluses with a lock-out interval of 8 minutes and background infusion rate at 1 mL/h for up to 72 hours after surgery.', 'armGroupLabels': ['Dexmedetomidine-esketamine group']}, {'name': 'Placebo', 'type': 'DRUG', 'description': 'Placebo (normal saline) is administered in the same rate and volume as that in the dexmedetomidine-esketamine group. Patient-controlled intravenous analgesia is established with 100 μg sufentanil, diluted to 100 mL with normal saline, and programmed to deliver 2-mL boluses with a lock-out interval of 8 minutes and background infusion rate at 1 mL/h for up to 72 hours after surgery.', 'armGroupLabels': ['Placebo group']}]}, 'contactsLocationsModule': {'locations': [{'zip': '100034', 'city': 'Beijing', 'status': 'RECRUITING', 'country': 'China', 'contacts': [{'name': 'Mo Li, MD, PhD', 'role': 'CONTACT'}], 'facility': 'Peking University First Hospital', 'geoPoint': {'lat': 39.9075, 'lon': 116.39723}}], 'centralContacts': [{'name': 'Mo Li, MD, PhD', 'role': 'CONTACT', 'email': '2361011139@pku.edu.cn', 'phone': '+86 19801260665'}], 'overallOfficials': [{'name': 'Dong-Xin Wang', 'role': 'STUDY_CHAIR', 'affiliation': 'Dong-Xin Wang, MD, PhD, Peking University First Hospital'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Peking University First Hospital', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Anesthesiologist, Department of Anesthesiology', 'investigatorFullName': 'Mo Li', 'investigatorAffiliation': 'Peking University First Hospital'}}}}