Reversal of Pipecuronium-induced Neuromuscular Blockade With Sugammadex During Sevoflurane Anesthesia

NCT ID: NCT07044193

Last Updated: 2025-06-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-06-26

Study Completion Date

2028-12-31

Brief Summary

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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.

Detailed Description

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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.

Therefore, adequate reversal of pipucornium induced neuromuscular blockade is crucial as a patient safety criterion.

Neuromuscular 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 .

Allergic 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.

The 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.

Conditions

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Neuromuscular Blocking Agents Residual Neuromuscular Block Reversal of Neuromuscular Blockade

Keywords

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reversal of neuromuscular blockade

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

controlled, randomised
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Rocuronium bromide as a control muscle relaxant agent in comparison to pipecuronium bromide.

Rocuronium bromide induced neuromuscular blockade antagonised by sugammadex as a control.

Group Type ACTIVE_COMPARATOR

Rocuronium bromide

Intervention Type DRUG

Muscle relaxation with rocuronium as a control

Reversal of pipecuronium induced neuromuscular blockade using sugammadex.

Reversal of pipecuronium induced neuromuscular blockade using sugammadex.

Group Type EXPERIMENTAL

pipecuronium bromide

Intervention Type DRUG

Investigation of muscle relaxation with pipecuronium bromide

Interventions

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pipecuronium bromide

Investigation of muscle relaxation with pipecuronium bromide

Intervention Type DRUG

Rocuronium bromide

Muscle relaxation with rocuronium as a control

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 80 adult general surgery and neurosurgical patients are enrolled in the study after giving an informed written consent regarding their participation.
* Age: between 18-65 years;
* ASA score: 1-3;
* BMI 18.5-25 (normal body weight);
* Males and females were recruited in an equal ratio;
* Minimal surgical time of at least ≥ 40 minutes;
* Procedures requiring endotracheal intubation;

Exclusion Criteria

* Diseases affecting neuromuscular function (myopathies, severe liver and kidney failure);

* Drugs affecting neuromuscular function (magnesium, aminoglycosides);
* Difficult airway, or anticipated difficult intubation;
* Pregnancy (a pregnancy test is performed in women of childbearing age to rule out pregnancy);
* Breast-feeding;
* Acute surgery;
* COPD
* Glaucoma
* History of previous allergic/anaphylactic reactions
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Tamas Vegh, MD

OTHER

Sponsor Role lead

Responsible Party

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Tamas Vegh, MD

MD PhD

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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University of Debrecen, Department of Anesthesiology and Intensive Care

Debrecen, Hajdú-Bihar, Hungary

Site Status

Countries

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Hungary

Central Contacts

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László Asztalos, MD, PhD

Role: CONTACT

Phone: +36307371315

Email: [email protected]

Mena Boktor Ajeeb, MD

Role: CONTACT

Phone: +36705873304

Email: [email protected]

Facility Contacts

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László Asztalos, MD PhD

Role: primary

Mena Boktor Ajeeb, MD

Role: backup

References

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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.

Reference Type BACKGROUND
PMID: 29200077 (View on PubMed)

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.

Reference Type BACKGROUND
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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.

Reference Type BACKGROUND
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Reference Type BACKGROUND
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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.

Reference Type BACKGROUND
PMID: 30169407 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25923435 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23665915 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20876699 (View on PubMed)

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.

Reference Type BACKGROUND
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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.

Reference Type BACKGROUND
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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.

Reference Type BACKGROUND
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Reference Type BACKGROUND
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Study Documents

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Document Type: Study Protocol

View Document

Other Identifiers

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DE RKEB/IKEB 7108-2025

Identifier Type: OTHER

Identifier Source: secondary_id

NNGYK/ETGY/08365-4/2025

Identifier Type: OTHER

Identifier Source: secondary_id

AITT 2025/2

Identifier Type: -

Identifier Source: org_study_id