Ignite Creation Date:
2025-12-24 @ 2:52 PM
Ignite Modification Date:
2025-12-24 @ 2:52 PM
Study NCT ID:
NCT04791059
Status:
COMPLETED
Last Update Posted:
2022-12-13
First Post:
2021-03-08
Is Possible Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Low-dose S-ketamine and Dexmedetomidine in Combination With Opioids for Postoperative Analgesia
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'C000629870', 'term': 'Esketamine'}, {'id': 'D020927', 'term': 'Dexmedetomidine'}, {'id': 'D017409', 'term': 'Sufentanil'}], 'ancestors': [{'id': 'D007093', 'term': 'Imidazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D005283', 'term': 'Fentanyl'}, {'id': 'D010880', 'term': 'Piperidines'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 200}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2021-04-09', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-12', 'completionDateStruct': {'date': '2022-10-07', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2022-12-12', 'studyFirstSubmitDate': '2021-03-08', 'studyFirstSubmitQcDate': '2021-03-08', 'lastUpdatePostDateStruct': {'date': '2022-12-13', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2021-03-10', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-09-07', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Percent of patients with moderate to severe pain within 72 hours', 'timeFrame': 'Up to 72 hours after surgery', 'description': 'Pain severity is evaluated with the Numeric Rating Scale (NRS, an 11-point scale where 0 = no pain and 10 = the worst pain) twice daily (8:00-10:00 and 18:00-20:00) at rest and with movement. Moderate to severe pain is defined as any NRS pain score of 4 or higher.'}], 'secondaryOutcomes': [{'measure': 'NRS pain score (at rest and with movement) at various timepoints after surgery', 'timeFrame': 'Up to 72 hours after surgery', 'description': 'Pain severity is evaluated with the Numeric Rating Scale (NRS, an 11-point scale where 0 = no pain and 10 = the worst pain) twice daily (8:00-10:00 and 18:00-20:00) at rest and with movement. Moderate to severe pain is defined as any NRS pain score of 4 or higher.'}, {'measure': 'Cumulative opioid consumption', 'timeFrame': 'Up to 72 hours after surgery', 'description': 'Cumulative opioid consumption'}, {'measure': 'Cumulative analgesic consumption', 'timeFrame': 'Up to 72 hours after surgery', 'description': 'Cumulative analgesic consumption'}, {'measure': 'Agitation and sedation score at various timepoints after surgery', 'timeFrame': 'Up to the 5th day after surgery', 'description': 'Agitation and sedation score is evaluated with the Richmond Agitation and Sedation Scale (RASS, with scores ranging from -5 \\[unarousable\\] to +4 \\[combative\\] and 0 indicates alert and calm) twice daily (8:00-10:00 and 18:00-20:00).'}, {'measure': 'Incidence of postoperative delirium within the first 5 days', 'timeFrame': 'Up to the 5th day after surgery', 'description': 'Delirium is assessed with the Three-dimensional Confusion Assessment Method (3D CAM) twice daily (8:00-10:00 and 18:00-20:00).'}, {'measure': 'Subjective sleep quality during the first 5 postoperative days', 'timeFrame': 'Up to the 5th day after surgery', 'description': 'Subjective sleep quality is evaluated with the Numeric Rating Scale (NRS, an 11-point scale where 0 = the best sleep and 10 = no sleep at all) once daily (8:00-10:00)'}, {'measure': 'Length of stay in hospital after surgery', 'timeFrame': 'Up to 30 days after surgery', 'description': 'Length of stay in hospital after surgery'}, {'measure': 'Duration requiring analgesics within 30 days after surgery', 'timeFrame': 'Up to 30 days after surgery', 'description': 'Duration requiring analgesics within 30 days after surgery'}, {'measure': 'Incidence of postoperative complications within 30 days', 'timeFrame': 'Up to 30 days after surgery', 'description': 'Postoperative complications are defined as new-onset medical conditions that were deemed harmful and required therapeutic intervention (i.e., grade II or higher on the Clavien-Dindo classification)'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Scoliosis correction', 'Postoperative analgesia', 'S-ketamine', 'Dexmedetomidine', 'Sufentanil'], 'conditions': ['Scoliosis Correction', 'Postoperative Analgesia', 'S-ketamine', 'Dexmedetomidine', 'Sufentanil']}, 'referencesModule': {'references': [{'pmid': '23392233', 'type': 'BACKGROUND', 'citation': 'Gerbershagen HJ, Aduckathil S, van Wijck AJ, Peelen LM, Kalkman CJ, Meissner W. Pain intensity on the first day after surgery: a prospective cohort study comparing 179 surgical procedures. Anesthesiology. 2013 Apr;118(4):934-44. doi: 10.1097/ALN.0b013e31828866b3.'}, {'pmid': '23374545', 'type': 'BACKGROUND', 'citation': 'Hussain A, Erdek M. Interventional pain management for failed back surgery syndrome. Pain Pract. 2014 Jan;14(1):64-78. doi: 10.1111/papr.12035. Epub 2013 Feb 3.'}, {'pmid': '30214945', 'type': 'BACKGROUND', 'citation': 'Seki H, Ideno S, Ishihara T, Watanabe K, Matsumoto M, Morisaki H. Postoperative pain management in patients undergoing posterior spinal fusion for adolescent idiopathic scoliosis: a narrative review. Scoliosis Spinal Disord. 2018 Sep 12;13:17. doi: 10.1186/s13013-018-0165-z. eCollection 2018.'}, {'pmid': '29510816', 'type': 'BACKGROUND', 'citation': 'Nielsen RV. Adjuvant analgesics for spine surgery. Dan Med J. 2018 Mar;65(3):B5468.'}, {'pmid': '30570761', 'type': 'BACKGROUND', 'citation': 'Brinck EC, Tiippana E, Heesen M, Bell RF, Straube S, Moore RA, Kontinen V. Perioperative intravenous ketamine for acute postoperative pain in adults. Cochrane Database Syst Rev. 2018 Dec 20;12(12):CD012033. doi: 10.1002/14651858.CD012033.pub4.'}, {'pmid': '30041987', 'type': 'BACKGROUND', 'citation': 'Bartova L, Papageorgiou K, Milenkovic I, Dold M, Weidenauer A, Willeit M, Winkler D, Kasper S. Rapid antidepressant effect of S-ketamine in schizophrenia. Eur Neuropsychopharmacol. 2018 Aug;28(8):980-982. doi: 10.1016/j.euroneuro.2018.05.007. Epub 2018 Jul 2.'}, {'pmid': '29736744', 'type': 'BACKGROUND', 'citation': 'Molero P, Ramos-Quiroga JA, Martin-Santos R, Calvo-Sanchez E, Gutierrez-Rojas L, Meana JJ. Antidepressant Efficacy and Tolerability of Ketamine and Esketamine: A Critical Review. CNS Drugs. 2018 May;32(5):411-420. doi: 10.1007/s40263-018-0519-3.'}, {'pmid': '32015715', 'type': 'BACKGROUND', 'citation': 'Canuso CM, Singh JB, Fedgchin M, Alphs L, Lane R, Lim P, Pinter C, Hough D, Sanacora G, Manji H, Drevets WC. Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study. Focus (Am Psychiatr Publ). 2019 Jan;17(1):55-65. doi: 10.1176/appi.focus.17105. Epub 2019 Jan 7.'}, {'pmid': '23893490', 'type': 'BACKGROUND', 'citation': 'Segmiller F, Ruther T, Linhardt A, Padberg F, Berger M, Pogarell O, Moller HJ, Kohler C, Schule C. Repeated S-ketamine infusions in therapy resistant depression: a case series. J Clin Pharmacol. 2013 Sep;53(9):996-8. doi: 10.1002/jcph.122. Epub 2013 Jul 24. No abstract available.'}, {'pmid': '11936706', 'type': 'BACKGROUND', 'citation': 'Persson J, Hasselstrom J, Maurset A, Oye I, Svensson JO, Almqvist O, Scheinin H, Gustafsson LL, Almqvist O. Pharmacokinetics and non-analgesic effects of S- and R-ketamines in healthy volunteers with normal and reduced metabolic capacity. Eur J Clin Pharmacol. 2002 Feb;57(12):869-75. doi: 10.1007/s002280100353.'}, {'pmid': '9278550', 'type': 'BACKGROUND', 'citation': 'Stone LS, MacMillan LB, Kitto KF, Limbird LE, Wilcox GL. The alpha2a adrenergic receptor subtype mediates spinal analgesia evoked by alpha2 agonists and is necessary for spinal adrenergic-opioid synergy. J Neurosci. 1997 Sep 15;17(18):7157-65. doi: 10.1523/JNEUROSCI.17-18-07157.1997.'}, {'pmid': '29149140', 'type': 'BACKGROUND', 'citation': 'Peng K, Zhang J, Meng XW, Liu HY, Ji FH. Optimization of Postoperative Intravenous Patient-Controlled Analgesia with Opioid-Dexmedetomidine Combinations: An Updated Meta-Analysis with Trial Sequential Analysis of Randomized Controlled Trials. Pain Physician. 2017 Nov;20(7):569-596.'}, {'pmid': '27571256', 'type': 'BACKGROUND', 'citation': 'Wu XH, Cui F, Zhang C, Meng ZT, Wang DX, Ma J, Wang GF, Zhu SN, Ma D. Low-dose Dexmedetomidine Improves Sleep Quality Pattern in Elderly Patients after Noncardiac Surgery in the Intensive Care Unit: A Pilot Randomized Controlled Trial. Anesthesiology. 2016 Nov;125(5):979-991. doi: 10.1097/ALN.0000000000001325.'}, {'pmid': '28654556', 'type': 'BACKGROUND', 'citation': 'Gao Y, Deng X, Yuan H, Leng Y, Zhang T, Xu X, Tian S, Fang J, Ouyang W, Wu X. Patient-controlled Intravenous Analgesia With Combination of Dexmedetomidine and Sufentanil on Patients After Abdominal Operation: A Prospective, Randomized, Controlled, Blinded, Multicenter Clinical Study. Clin J Pain. 2018 Feb;34(2):155-161. doi: 10.1097/AJP.0000000000000527.'}, {'pmid': '27327855', 'type': 'BACKGROUND', 'citation': 'Bornemann-Cimenti H, Wejbora M, Michaeli K, Edler A, Sandner-Kiesling A. The effects of minimal-dose versus low-dose S-ketamine on opioid consumption, hyperalgesia, and postoperative delirium: a triple-blinded, randomized, active- and placebo-controlled clinical trial. Minerva Anestesiol. 2016 Oct;82(10):1069-1076. Epub 2016 Jun 21.'}, {'pmid': '32443302', 'type': 'BACKGROUND', 'citation': 'Lee KH, Lee SJ, Park JH, Kim SH, Lee H, Oh DS, Kim YH, Park YH, Kim H, Lee SE. Analgesia for spinal anesthesia positioning in elderly patients with proximal femoral fractures: Dexmedetomidine-ketamine versus dexmedetomidine-fentanyl. Medicine (Baltimore). 2020 May;99(20):e20001. doi: 10.1097/MD.0000000000020001.'}, {'pmid': '32594705', 'type': 'BACKGROUND', 'citation': 'Hu ZC, Xu G, Zhang XW, Ma K, Jin JJ, Li PS. [Meta-analysis of the effects of dexmedetomidine combined with ketamine during dressing changes in burn patients]. Zhonghua Shao Shang Za Zhi. 2020 Jun 20;36(6):458-464. doi: 10.3760/cma.j.cn501120-20190327-00145. Chinese.'}, {'pmid': '31260468', 'type': 'BACKGROUND', 'citation': 'Meng ZT, Cui F, Li XY, Wang DX. Epidural morphine improves postoperative analgesia in patients after total knee arthroplasty: A randomized controlled trial. PLoS One. 2019 Jul 1;14(7):e0219116. doi: 10.1371/journal.pone.0219116. eCollection 2019.'}, {'pmid': '19638912', 'type': 'BACKGROUND', 'citation': 'Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, de Santibanes E, Pekolj J, Slankamenac K, Bassi C, Graf R, Vonlanthen R, Padbury R, Cameron JL, Makuuchi M. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009 Aug;250(2):187-96. doi: 10.1097/SLA.0b013e3181b13ca2.'}, {'pmid': '37302963', 'type': 'DERIVED', 'citation': 'Zhang Y, Cui F, Ma JH, Wang DX. Mini-dose esketamine-dexmedetomidine combination to supplement analgesia for patients after scoliosis correction surgery: a double-blind randomised trial. Br J Anaesth. 2023 Aug;131(2):385-396. doi: 10.1016/j.bja.2023.05.001. Epub 2023 Jun 9.'}]}, 'descriptionModule': {'briefSummary': 'Scoliosis correction surgery is followed with severe pain. Patients after scoliosis correction surgery usually require high dose opioids and long duration analgesia, which may increase side effects and even drug tolerance. S-ketamine is the pure dextrorotatory enantiomer of ketamine with stronger analgesic effect and less side effects, but mental side effects is a major concern. Dexmedetomidine can be used as an analgesic supplement; it also improves sleep quality in postoperative patients. We hypothesize that low-dose ketamine and dexmedetomidine in combination with opioids may have synergistic effect in analgesia and reduce drug-related side effects. This study aims to explore the effect of low-dose of S-ketamine and dexmedetomidine in combination with opioids for postoperative patient-controlled intravenous analgesia in patients following scoliosis correction surgery.', 'detailedDescription': 'Scoliosis correction surgery is followed with severe pain. The reported median pain score on the first day after surgery is median 7 (IQR 4, 8); with an incidence of persistent postoperative pain from 5% to 75%. Most patients undergoing this surgery are young and adolescents; they are sensitive to pain and usually require higher dose analgesics and a long duration analgesia. The total dose of opioids required for postoperative analgesia is about 2-4 times higher than that after other surgeries. But even with high dose opioids, the analgesic effect remains unsatisfied. Furthermore, high dose opioids may cause side effects such as respiratory depression, drowsiness, nausea, vomiting, skin itching, and even drug tolerance.\n\nKetamine is a noncompetitive N-methyl-D-aspartate receptor antagonist (NMDA) with analgesic and anti-hyperalgesia effects. It is widely used for anesthesia induction in critically ill patients, pediatric anesthesia and postoperative analgesia. The advantages of ketamine include mild influence on respiratory and circulatory function, and good analgesic effect. Recent guidelines recommends the use of low-dose ketamine infusion for postoperative analgesia in patients with moderate to severe pain, in order to reduce the consumption of opioids. S-ketamine is the pure dextrorotatory enantiomer of ketamine with stronger analgesic effect and lower incidence of adverse reactions.\n\nDexmedetomidine is a highly selective α2 receptor agonist with effects of antianxiety, sedation and analgesia. When used as a supplement, it improves analgesic effect, and reduces opioid consumption and opioid related adverse reactions. In the same time, dexmedetomidine activates the endogenous sleep pathway and improves sleep quality by prolonging total sleep time, increasing sleep efficiency, and promoting subjective sleep quality.\n\nIt is worthy to note that ketamine can produce adverse reactions such as agitation, delirium and anxiety, and increase the incidence of hallucinations and nightmares when the given dose is slightly higher; whereas the sedative effect of dexmedetomidine may help to reduce the adverse effects of ketamine. We hypothesize that low-dose ketamine and dexmedetomidine in combination with opioids may have synergistic effects in postoperative analgesia and reduce drug-related adverse reactions.\n\nThis study aims to explore the effect of low-dose of S-ketamine and dexmedetomidine in combination with opioids for postoperative patient-controlled intravenous analgesia in patients following scoliosis correction surgery.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age ≥ 18 years old, body weight ≥ 40 kg;\n* Scheduled to undergo scoliosis correction with pedicle screw fixation;\n* Planned to use patient-controlled intravenous analgesia after surgery.\n\nExclusion Criteria:\n\n* Refused to participate in the study;\n* Preoperative sick sinus syndrome, severe sinus bradycardia (heart rate \\< 50 beats/min), atrioventricular block grade II or above without pacemaker; or comorbid with congenital heart disease, arrhythmia, or other serious cardiovascular diseases with a cardiac function grade ≥ III;\n* Patients with obstructive sleep apnea syndrome, or a STOP-Bang score ≥ 3 in combination with a serum HCO3- level ≥ 28 mmol/L;\n* History of hyperthyroidism and pheochromocytoma;\n* History of schizophrenia, epilepsy, myasthenia gravis, or delirium;\n* Severe liver dysfunction (child Pugh grade C), severe renal dysfunction (preoperative dialysis), or American Society of Anesthesiologists grade ≥ IV;\n* Barrier in communication;\n* Other conditions that are considered unsuitable for study participation.'}, 'identificationModule': {'nctId': 'NCT04791059', 'briefTitle': 'Low-dose S-ketamine and Dexmedetomidine in Combination With Opioids for Postoperative Analgesia', 'organization': {'class': 'OTHER', 'fullName': 'Peking University First Hospital'}, 'officialTitle': 'Low-dose S-ketamine and Dexmedetomidine in Combination With Opioids for Patient-controlled Analgesia After Scoliosis Correction Surgery: a Randomized, Double-blind, Placebo-controlled Trial', 'orgStudyIdInfo': {'id': '2020-465'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Combined analgesia group', 'description': 'Patient-controlled analgesia is established with S-ketamine 50 mg, dexmedetomidine 200 microgram, and sufentanil 4 microgram/kg (maximum 250 microgram), diluted with normal saline to 200 ml, and programmed to administer 2-ml boluses with a lock-out interval of 8 minutes and a background infusion rate at 1 ml/h.', 'interventionNames': ['Drug: S-ketamine', 'Drug: Dexmedetomidine', 'Drug: Sufentanil']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Control group', 'description': 'Patient-controlled analgesia is established with sufentanil 4 microgram/kg (maximum 250 microgram), diluted with normal saline to 200 ml, and programmed to administer 2-ml boluses with a lock-out interval of 8 minutes and a background infusion rate at 1 ml/h.', 'interventionNames': ['Drug: Sufentanil']}], 'interventions': [{'name': 'S-ketamine', 'type': 'DRUG', 'description': 'S-ketamine 50 mg is included in the mixture for patient-controlled analgesia.', 'armGroupLabels': ['Combined analgesia group']}, {'name': 'Dexmedetomidine', 'type': 'DRUG', 'description': 'Dexmedetomidine 200 microgram is included in the mixture for patient-controlled analgesia.', 'armGroupLabels': ['Combined analgesia group']}, {'name': 'Sufentanil', 'type': 'DRUG', 'description': 'Sufentanil 4 microgram/kg (maximum 250 microgram) is included in the mixture for patient-controlled analgesia.', 'armGroupLabels': ['Combined analgesia group', 'Control group']}]}, 'contactsLocationsModule': {'locations': [{'zip': '100034', 'city': 'Beijing', 'state': 'Beijing Municipality', 'country': 'China', 'facility': 'Peking University First Hospital', 'geoPoint': {'lat': 39.9075, 'lon': 116.39723}}], 'overallOfficials': [{'name': 'Dong-Xin Wang, MD,PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Peking University First Hospital'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Peking University First Hospital', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor and Chairman, Department of Anesthesiology and Critical Care Medicine', 'investigatorFullName': 'Dong-Xin Wang', 'investigatorAffiliation': 'Peking University First Hospital'}}}}