Ignite Creation Date:
2025-12-25 @ 1:20 AM
Ignite Modification Date:
2026-01-01 @ 1:44 PM
Study NCT ID:
NCT07044193
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-06-29
First Post:
2025-06-19
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Reversal of Pipecuronium-induced Neuromuscular Blockade With Sugammadex During Sevoflurane Anesthesia
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D055191', 'term': 'Delayed Emergence from Anesthesia'}], 'ancestors': [{'id': 'D011183', 'term': 'Postoperative Complications'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D017300', 'term': 'Pipecuronium'}, {'id': 'D000077123', 'term': 'Rocuronium'}], 'ancestors': [{'id': 'D010879', 'term': 'Piperazines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D000732', 'term': 'Androstanols'}, {'id': 'D000731', 'term': 'Androstanes'}, {'id': 'D013256', 'term': 'Steroids'}, {'id': 'D000072473', 'term': 'Fused-Ring Compounds'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'controlled, randomised'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 80}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2025-06-26', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-06', 'completionDateStruct': {'date': '2028-12-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-06-27', 'studyFirstSubmitDate': '2025-06-19', 'studyFirstSubmitQcDate': '2025-06-27', 'lastUpdatePostDateStruct': {'date': '2025-06-29', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2025-06-29', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-12-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'The incidence of allergic/anaphylactic reactions', 'timeFrame': 'From induction to up to 30 minutes postoperatively', 'description': "The incidence of allergic/anaphylactic reactions associated with muscle relaxant and reversal agents' administration."}, {'measure': 'Time to achieving a TOF ratio of 1.0', 'timeFrame': 'the time elapsed until the onset of Summadex which is within 5 minutes', 'description': 'The time elapsed between Sugammadex administration and achieving a TOF ratio of 1.0'}, {'measure': 'Doses of the muscle ralaxants', 'timeFrame': 'from induction to reversal according to the surgical time', 'description': 'Comparison of sugammadex doses required to reverse the effects of the study focused two muscle relaxants.'}], 'primaryOutcomes': [{'measure': 'Time till TOF ratio of 0.9', 'timeFrame': 'from reversal to extubation within 5 minutes as per the onset of time of Sugammadex', 'description': 'The time between the start of sugammadex administration and reaching a TOF ratio of 0.9 will be the primary efficacy endpoint of the study.'}], 'secondaryOutcomes': [{'measure': 'Incidence of residual neuromuscular blockade', 'timeFrame': '30 minutes after extubation', 'description': 'The Prevalence of TOF \\<0.9 in the postoperative period.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['reversal of neuromuscular blockade'], 'conditions': ['Neuromuscular Blocking Agents', 'Residual Neuromuscular Block', 'Reversal of Neuromuscular Blockade']}, 'referencesModule': {'availIpds': [{'url': 'https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2025-521375-31-00', 'type': 'Study Protocol'}], 'references': [{'pmid': '29200077', 'type': 'BACKGROUND', 'citation': 'Naguib M, Brull SJ, Kopman AF, Hunter JM, Fulesdi B, Arkes HR, Elstein A, Todd MM, Johnson KB. Consensus Statement on Perioperative Use of Neuromuscular Monitoring. Anesth Analg. 2018 Jul;127(1):71-80. doi: 10.1213/ANE.0000000000002670.'}, {'pmid': '33204386', 'type': 'BACKGROUND', 'citation': 'Cardona V, Ansotegui IJ, Ebisawa M, El-Gamal Y, Fernandez Rivas M, Fineman S, Geller M, Gonzalez-Estrada A, Greenberger PA, Sanchez Borges M, Senna G, Sheikh A, Tanno LK, Thong BY, Turner PJ, Worm M. World allergy organization anaphylaxis guidance 2020. World Allergy Organ J. 2020 Oct 30;13(10):100472. doi: 10.1016/j.waojou.2020.100472. eCollection 2020 Oct.'}, {'pmid': '37345870', 'type': 'BACKGROUND', 'citation': 'Fuchs-Buder T, Brull SJ, Fagerlund MJ, Renew JR, Cammu G, Murphy GS, Warle M, Vested M, Fulesdi B, Nemes R, Columb MO, Damian D, Davis PJ, Iwasaki H, Eriksson LI. Good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents III: The 2023 Geneva revision. Acta Anaesthesiol Scand. 2023 Sep;67(8):994-1017. doi: 10.1111/aas.14279. Epub 2023 Jun 22.'}, {'pmid': '4819478', 'type': 'BACKGROUND', 'citation': 'Samuel WM, Holmes JC. Search for elaphostrongyline parasites in cervids from Alberta. Can J Zool. 1974 Mar;52(3):401-3. doi: 10.1139/z74-048. No abstract available.'}, {'pmid': '30169407', 'type': 'BACKGROUND', 'citation': 'Tassonyi E, Asztalos L, Szabo-Maak Z, Nemes R, Pongracz A, Lengyel S, Fulesdi B. Reversal of Deep Pipecuronium-Induced Neuromuscular Block With Moderate Versus Standard Dose of Sugammadex: A Randomized, Double-Blind, Noninferiority Trial. Anesth Analg. 2018 Dec;127(6):1344-1350. doi: 10.1213/ANE.0000000000003719.'}, {'pmid': '25923435', 'type': 'BACKGROUND', 'citation': 'Tassonyi E, Pongracz A, Nemes R, Asztalos L, Lengyel S, Fulesdi B. Reversal of Pipecuronium-Induced Moderate Neuromuscular Block with Sugammadex in the Presence of a Sevoflurane Anesthetic: A Randomized Trial. Anesth Analg. 2015 Aug;121(2):373-80. doi: 10.1213/ANE.0000000000000766.'}, {'pmid': '23665915', 'type': 'BACKGROUND', 'citation': 'Pongracz A, Szatmari S, Nemes R, Fulesdi B, Tassonyi E. Reversal of neuromuscular blockade with sugammadex at the reappearance of four twitches to train-of-four stimulation. Anesthesiology. 2013 Jul;119(1):36-42. doi: 10.1097/ALN.0b013e318297ce95.'}, {'pmid': '20876699', 'type': 'BACKGROUND', 'citation': 'Puhringer FK, Gordon M, Demeyer I, Sparr HJ, Ingimarsson J, Klarin B, van Duijnhoven W, Heeringa M. Sugammadex rapidly reverses moderate rocuronium- or vecuronium-induced neuromuscular block during sevoflurane anaesthesia: a dose-response relationship. Br J Anaesth. 2010 Nov;105(5):610-9. doi: 10.1093/bja/aeq226. Epub 2010 Sep 28.'}, {'pmid': '19933538', 'type': 'BACKGROUND', 'citation': 'Duvaldestin P, Kuizenga K, Saldien V, Claudius C, Servin F, Klein J, Debaene B, Heeringa M. A randomized, dose-response study of sugammadex given for the reversal of deep rocuronium- or vecuronium-induced neuromuscular blockade under sevoflurane anesthesia. Anesth Analg. 2010 Jan 1;110(1):74-82. doi: 10.1213/ANE.0b013e3181c3be3c. Epub 2009 Nov 21.'}, {'pmid': '17264722', 'type': 'BACKGROUND', 'citation': 'Suy K, Morias K, Cammu G, Hans P, van Duijnhoven WG, Heeringa M, Demeyer I. Effective reversal of moderate rocuronium- or vecuronium-induced neuromuscular block with sugammadex, a selective relaxant binding agent. Anesthesiology. 2007 Feb;106(2):283-8. doi: 10.1097/00000542-200702000-00016.'}, {'pmid': '20357160', 'type': 'BACKGROUND', 'citation': 'Abrishami A, Ho J, Wong J, Yin L, Chung F. Cochrane corner: sugammadex, a selective reversal medication for preventing postoperative residual neuromuscular blockade. Anesth Analg. 2010 Apr 1;110(4):1239. doi: 10.1213/ANE.0b013e3181ce8d5e.'}, {'pmid': '11753000', 'type': 'BACKGROUND', 'citation': 'Kirkegaard H, Heier T, Caldwell JE. Efficacy of tactile-guided reversal from cisatracurium-induced neuromuscular block. Anesthesiology. 2002 Jan;96(1):45-50. doi: 10.1097/00000542-200201000-00013.'}], 'seeAlsoLinks': [{'url': 'https://pubmed.ncbi.nlm.nih.gov/20357160/', 'label': 'Related Info'}, {'url': 'https://pubmed.ncbi.nlm.nih.gov/11753000/', 'label': 'Related Info'}, {'url': 'https://pubmed.ncbi.nlm.nih.gov/17264722/', 'label': 'Related Info'}, {'url': 'https://pubmed.ncbi.nlm.nih.gov/19933538/', 'label': 'Related Info'}, {'url': 'https://pubmed.ncbi.nlm.nih.gov/20876699/', 'label': 'Related Info'}, {'url': 'https://pubmed.ncbi.nlm.nih.gov/23665915/', 'label': 'Related Info'}, {'url': 'https://pubmed.ncbi.nlm.nih.gov/25923435/', 'label': 'Related Info'}, {'url': 'https://pubmed.ncbi.nlm.nih.gov/30169407/', 'label': 'Related Info'}, {'url': 'https://pubmed.ncbi.nlm.nih.gov/4819478/', 'label': 'Related Info'}, {'url': 'https://pubmed.ncbi.nlm.nih.gov/37345870/', 'label': 'Related Info'}, {'url': 'https://pubmed.ncbi.nlm.nih.gov/33204386/', 'label': 'Related Info'}, {'url': 'https://pubmed.ncbi.nlm.nih.gov/29200077/', 'label': 'Related Info'}]}, 'descriptionModule': {'briefSummary': 'Safety during modern practice of anaesthesia is of great concern. Patients admitted daily for surgical procedures undergoing general anaesthesia for different types of operations are exposed to different risks, starting from the anaesthesia and ending with the surgical intervention. Aim of the study is to provide a comprehensive and evidence based data regarding the safety of the neuromuscular blocking agents used in modern anaesthesia practice, precisely Rocuronium and Pipecuronium, as well as the reversal agents such as Sugammadex, which is the sole agent in use in practice nowadays. A routine anaesthetic practice will be performed during the whole period of our study after strict patient selection criteria. Intraoperative standard monitoring as per local and international guidelines will be applied, this includes Spo2, ECG, NIBP/IBP, etCO2, BIS and Tetragaph for neuromuscular blockade monitoring. After induction of anaesthesia and prior to the administration of the muscle relaxant agent, a TOFC (Train of Four Count) will be registered as the starting point. Throughout the anaesthetic time, there will be continuous TOF monitoring. The anaesthesia will be maintained by sevoflurane. Also, the recruited samples will be divided according to the neuromuscular blockade agents administered, either Rocuronium or Pipecuronium. At the end of the surgical procedure, the time lapse between the administration of the reversal agent Sugammadex and a TOF ratio of 0.9 is registered as our primary end point. TOF measures will be performed in the postoperative period, to make sure there is no residual neuromuscular blockade in the early postoperative phase. The study will not only monitor the safety of the neuromuscular blocking agents in use, but will also monitor any signs of anaphylaxis due to their administration both intra and postoperatively.', 'detailedDescription': "Pipecuronium bromide (Arduan®) is a long-acting (45-100 min) aminosteroid-type muscle relaxant which has no cardiovascular side effects, neither causes histamine release and it is primarily excreted from the body via the liver and partially via the kidney. These properties make it the drug of choice Pipecuronium in long (≥100 min) operations and intensive care units. Currently, it is the only available long acting muscle relaxant in Hungary. Pipecuronium is also licensed and used regularly in other countries as per (www.drugs.com/international). Residual neuromuscular blockade is considered a characteristic of the long-acting muscle relaxants, which in turn could lead to postoperative respiratory complications.\n\nTherefore, adequate reversal of pipucornium induced neuromuscular blockade is crucial as a patient safety criterion.\n\nNeuromuscular block reversal using neostigmine has proved to be non-reliable. There is a good evidence of the risks and inadequacy of neostigmine reversal, particularly in the case of inhalational anaesthetics . Therefore, the use of a more effective and safe antagonist may offer significant advantages in the use of Pipecuronium and open a new perspective in neuromuscular blockade reversal. Sugammadex (Bridion®) is the first muscle relaxant antagonist to bind and neutralise muscle relaxants in the plasma. The cyclodextrin compound was originally developed to antagonize Rocuronium block, but it is also able to reverse the Vecuronium bromide-induced block, due to structure similarity. Sugammadex binds to Pipecuronium bromide, which also has an aminosteroid structure, and has an affinity for it that is about ten times that of Rocuronium bromide http://www.pmda.go.jp/files/000153538.pdf. Several studies have demonstrated the efficacy of Sugammadex in antagonizing Rocuronium-induced neuromuscular block, but in the international literature, few clinical data are available regarding the safety of Sugammadex as a reversal agent for Pipecuronium blockade. In a previous study was found that Sugammadex also antagonizes the residual effect of Pipecuronium when neuromuscular blockade already shows signs of spontaneous recovery: two muscle twitches (moderate, so-called TOF-Count 2 block) can be elicited by Train-of-Four (TOF) stimulation. Sugammadex at a relatively low dosage (1 mg/kg) was sufficient to achieve adequate effects in patients with moderate Pipecuronium-induced blockade (TOFC2). There was no postoperative muscle weakness or recurrence encountered. It was demonstrated that 2 mg/kg sugammadex can effectively reverse Pipecuronium-induced deep neuromuscular block. In this study, was also demonstrated that neither residual nor recurreIt that muscle relaxant effects should arise after antagonizing deep Pipecuronium block with Sugammadex .\n\nAllergic reactions may occur with the use of muscle relaxants. While Rocuronium bromide is the second most common cause anaphylactic reactions among muscle relaxants in use, which is not revealed in the case of Pipecuronium. No large case-control studies have yet been performed to investigate the safety of reversing Pipercuornium-induced blockade using Sugammadex, neither the incidence of postoperative residual neuromuscular block, nor the incidence of anaphylactic reactions post-administration.\n\nThe aim of present study is therefore to investigate the safety of Pipecuronium in comparison to Rocuronium bromide in surgical patients' population undergoing anaesthesia with sevoflurane. The study will evaluate the effective reversing ability of Sugammadex, assessing the incidence of postoperative residual neuromuscular block and the incidence of allergic reactions, nevertheless comparing different doses of sugammadex required to antagonise the effects of the two muscle relaxants."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* 80 adult general surgery and neurosurgical patients are enrolled in the study after giving an informed written consent regarding their participation.\n* Age: between 18-65 years;\n* ASA score: 1-3;\n* BMI 18.5-25 (normal body weight);\n* Males and females were recruited in an equal ratio;\n* Minimal surgical time of at least ≥ 40 minutes;\n* Procedures requiring endotracheal intubation;\n\nExclusion Criteria:\n\n* Diseases affecting neuromuscular function (myopathies, severe liver and kidney failure);\n\n * Drugs affecting neuromuscular function (magnesium, aminoglycosides);\n * Difficult airway, or anticipated difficult intubation;\n * Pregnancy (a pregnancy test is performed in women of childbearing age to rule out pregnancy);\n * Breast-feeding;\n * Acute surgery;\n * COPD\n * Glaucoma\n * History of previous allergic/anaphylactic reactions'}, 'identificationModule': {'nctId': 'NCT07044193', 'acronym': 'RPINMBWS', 'briefTitle': 'Reversal of Pipecuronium-induced Neuromuscular Blockade With Sugammadex During Sevoflurane Anesthesia', 'organization': {'class': 'OTHER', 'fullName': 'University of Debrecen'}, 'officialTitle': 'Reversal of Pipecuronium-induced Neuromuscular Blockade With Sugammadex During Sevoflurane Anesthesia: a Drug Safety Randomised Controlled Trial', 'orgStudyIdInfo': {'id': 'AITT 2025/2'}, 'secondaryIdInfos': [{'id': 'DE RKEB/IKEB 7108-2025', 'type': 'OTHER', 'domain': 'Regional and Institutional Ethics Committee University of Debrecen Clinical Center'}, {'id': 'NNGYK/ETGY/08365-4/2025', 'type': 'OTHER', 'domain': 'National Center for Public Health and Pharmacy Department of Clinical Research'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Rocuronium bromide as a control muscle relaxant agent in comparison to pipecuronium bromide.', 'description': 'Rocuronium bromide induced neuromuscular blockade antagonised by sugammadex as a control.', 'interventionNames': ['Drug: Rocuronium bromide']}, {'type': 'EXPERIMENTAL', 'label': 'Reversal of pipecuronium induced neuromuscular blockade using sugammadex.', 'description': 'Reversal of pipecuronium induced neuromuscular blockade using sugammadex.', 'interventionNames': ['Drug: pipecuronium bromide']}], 'interventions': [{'name': 'pipecuronium bromide', 'type': 'DRUG', 'description': 'Investigation of muscle relaxation with pipecuronium bromide', 'armGroupLabels': ['Reversal of pipecuronium induced neuromuscular blockade using sugammadex.']}, {'name': 'Rocuronium bromide', 'type': 'DRUG', 'description': 'Muscle relaxation with rocuronium as a control', 'armGroupLabels': ['Rocuronium bromide as a control muscle relaxant agent in comparison to pipecuronium bromide.']}]}, 'contactsLocationsModule': {'locations': [{'zip': '4032', 'city': 'Debrecen', 'state': 'Hajdú-Bihar', 'country': 'Hungary', 'contacts': [{'name': 'László Asztalos, MD PhD', 'role': 'CONTACT', 'email': 'asztaloslasz@gmail.com', 'phone': '+36307371315'}, {'name': 'Mena Boktor Ajeeb, MD', 'role': 'CONTACT', 'email': 'boktor.mena@med.unideb.hu', 'phone': '+36705873304'}, {'name': 'László Asztalos, MD PhD', 'role': 'PRINCIPAL_INVESTIGATOR'}, {'name': 'Mena Boktor Ajeeb, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Béla Fülesdi, MD, PhD, DSc', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Péter Filipcsuk, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Adrienn Pongrácz, MD PhD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Réka Nemes, MD PhD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Marianna Fedor, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'György Nagy, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Sorin Brull, MD, Professor', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Nouran Mohamed Elsayed Ahmed, medical student', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Omonigho Okoduwa, medical student', 'role': 'SUB_INVESTIGATOR'}], 'facility': 'University of Debrecen, Department of Anesthesiology and Intensive Care', 'geoPoint': {'lat': 47.53167, 'lon': 21.62444}}], 'centralContacts': [{'name': 'László Asztalos, MD, PhD', 'role': 'CONTACT', 'email': 'asztaloslasz@gmail.com', 'phone': '+36307371315'}, {'name': 'Mena Boktor Ajeeb, MD', 'role': 'CONTACT', 'email': 'boktor.mena@med.unideb.hu', 'phone': '+36705873304'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Tamas Vegh, MD', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'MD PhD', 'investigatorFullName': 'Tamas Vegh, MD', 'investigatorAffiliation': 'University of Debrecen'}}}}