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

June 27, 2025 updated by: Tamas Vegh, MD

Reversal of Pipecuronium-induced Neuromuscular Blockade With Sugammadex During Sevoflurane Anesthesia: a Drug Safety Randomised Controlled Trial

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

80

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Hungary
    • Hajdú-Bihar
      • Debrecen, Hajdú-Bihar, Hungary, 4032
        • University of Debrecen, Department of Anesthesiology and Intensive Care
        • Contact:
        • Contact:
        • Principal Investigator:
          • László Asztalos, MD PhD
        • Sub-Investigator:
          • Mena Boktor Ajeeb, MD
        • Sub-Investigator:
          • Béla Fülesdi, MD, PhD, DSc
        • Sub-Investigator:
          • Péter Filipcsuk, MD
        • Sub-Investigator:
          • Adrienn Pongrácz, MD PhD
        • Sub-Investigator:
          • Réka Nemes, MD PhD
        • Sub-Investigator:
          • Marianna Fedor, MD
        • Sub-Investigator:
          • György Nagy, MD
        • Sub-Investigator:
          • Sorin Brull, MD, Professor
        • Sub-Investigator:
          • Nouran Mohamed Elsayed Ahmed, medical student
        • Sub-Investigator:
          • Omonigho Okoduwa, medical student

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Rocuronium bromide as a control muscle relaxant agent in comparison to pipecuronium bromide.
Rocuronium bromide induced neuromuscular blockade antagonised by sugammadex as a control.
Drug: Rocuronium bromide
Muscle relaxation with rocuronium as a control
Experimental: Reversal of pipecuronium induced neuromuscular blockade using sugammadex.
Drug: pipecuronium bromide
Investigation of muscle relaxation with pipecuronium bromide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time till TOF ratio of 0.9
Time Frame: from reversal to extubation within 5 minutes as per the onset of time of Sugammadex
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.
from reversal to extubation within 5 minutes as per the onset of time of Sugammadex

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of residual neuromuscular blockade
Time Frame: 30 minutes after extubation
The Prevalence of TOF <0.9 in the postoperative period.
30 minutes after extubation

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
The incidence of allergic/anaphylactic reactions
Time Frame: From induction to up to 30 minutes postoperatively
The incidence of allergic/anaphylactic reactions associated with muscle relaxant and reversal agents' administration.
From induction to up to 30 minutes postoperatively
Time to achieving a TOF ratio of 1.0
Time Frame: the time elapsed until the onset of Summadex which is within 5 minutes
The time elapsed between Sugammadex administration and achieving a TOF ratio of 1.0
the time elapsed until the onset of Summadex which is within 5 minutes
Doses of the muscle ralaxants
Time Frame: from induction to reversal according to the surgical time
Comparison of sugammadex doses required to reverse the effects of the study focused two muscle relaxants.
from induction to reversal according to the surgical time

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tamas Vegh, MD

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 26, 2025

Primary Completion (Estimated)

December 31, 2028

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

June 19, 2025

First Submitted That Met QC Criteria

June 27, 2025

First Posted (Actual)

June 29, 2025

Study Record Updates

Last Update Posted (Actual)

June 29, 2025

Last Update Submitted That Met QC Criteria

June 27, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AITT 2025/2
  • DE RKEB/IKEB 7108-2025 (Other Identifier: Regional and Institutional Ethics Committee University of Debrecen Clinical Center)
  • NNGYK/ETGY/08365-4/2025 (Other Identifier: National Center for Public Health and Pharmacy Department of Clinical Research)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Study Data/Documents

  1. Study Protocol

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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