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

T

Tamas Vegh, MD

Status and phase

Not yet enrolling
Phase 4

Conditions

Neuromuscular Blocking Agents
Residual Neuromuscular Block
Reversal of Neuromuscular Blockade

Treatments

Drug: pipecuronium bromide
Drug: Rocuronium bromide

Study type

Interventional

Funder types

Other

Identifiers

NCT07044193
DE RKEB/IKEB 7108-2025 (Other Identifier)
NNGYK/ETGY/08365-4/2025 (Other Identifier)
AITT 2025/2

Details and patient eligibility

About

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.

Full 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.

Enrollment

80 estimated patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

80 participants in 2 patient groups

Rocuronium bromide as a control muscle relaxant agent in comparison to pipecuronium bromide.
Active Comparator group
Description:
Rocuronium bromide induced neuromuscular blockade antagonised by sugammadex as a control.
Treatment:
Drug: Rocuronium bromide
Reversal of pipecuronium induced neuromuscular blockade using sugammadex.
Experimental group
Description:
Reversal of pipecuronium induced neuromuscular blockade using sugammadex.
Treatment:
Drug: pipecuronium bromide

Trial contacts and locations

1

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Central trial contact

László Asztalos, MD, PhD; Mena Boktor Ajeeb, MD

Data sourced from clinicaltrials.gov

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