Low Dose of Sugammadex vs Neostigmine and Glycopyrrolate for the Reversal of Rocuronium

NCT ID: NCT05718934

Last Updated: 2024-02-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 144 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-08
• Study Completion Date: 2023-12-19

Brief Summary

The aim of this study is to compare the use of a low dose sugammadex and neostigmine combined to glycopyrrolate to reverse a rocuronium induced moderate neuromuscular blockade.

Detailed Description

Neuromuscular blocking agents (NMBAs) are administered by anesthesiologists for general anesthesia to facilitate endotracheal intubation and/or surgical conditions. Unfortunately, postoperative residual neuromuscular blockade (rNMB), is an adverse event usually observed after extubation in the postanesthesia care unit (PACU) after surgery. rNMB is associated with upper airway obstruction, reduced pharyngeal muscle coordination, decreased functional residual capacity, and impaired hypoxic ventilatory response and may lead to critical cardiopulmonary complications.To prevent those complications, monitoring NMBAs activity as well as appropriate reversal are crucial.

In the light of the strong evidence proving the superiority of sugammadex for the reversal of NMB, the investigators chose to examine whether a quarter dose (0.5 mg.kg-1) of sugammadex would be superior to neostigmine for the reversal of moderate NMB (TOF 1 to 3). The investigators believe that this strategy will encourage the routine use of sugammadex because of a drastically reduced cost per patient with an increased safety and less adverse events compared to neostigmine reversal.

This study will be conducted in a single center, double blinded, randomized controlled study.

Type of surgery: any surgery under general anesthesia in ASA 1-3 patients, fully consented.

In the OR, the investigators will place a standardized monitoring: ECG, non-invasive blood pressure and SpO2. The investigators will monitor the depth of anesthesia using the BIS index (Medtronic, Canada) and the intraoperative nociception balance using the NOL index (Medasense Ltd., Ramat Gan, Israel). Finally, the investigators will monitor neuromuscular blockade using TOF-scan® (Draeger, Mississauga, Canada). The stimulation electrodes will be placed on the forearm of the patient to monitor the response to ulnar stimulation of the adductor pollicis muscle.

The investigators will use adjusted body weight for the administration of the drugs used in our anesthesia protocol except for rocuronium, sugammadex and neostigmine that will be given based on the real actual body weight.

The primary objective of the study:

To compare the mean time for recovery of the TOF ratio to 0.9 (90%) at the end of the surgery for rocuronium induced moderate neuromuscular blockade (TOF 1 to 3 at the end of the surgery) in two groups: Group "N" for neostigmine and group "S" for sugammadex. Group N will receive the standard reversal (neostigmine 50 µg.kg-1 and glycopyrrolate 7 µg.kg-1) and group S will receive sugammadex 0.5 mg.kg-1.

Secondary objectives are listed below.

Based on a 2-sided alpha < 0.05 and 80% power, the investigators calculated that 64 patients per group was required to detect a clinically relevant effect size of 0.5 favouring S group. The sample size will be inflated to 144 (72 per group) to account for 10% withdrawals and loss of follow-up.

Study Duration: 12 months.

Study Center: Maisonneuve-Rosemont Hospital, CIUSSS de l'Est de l'Ile de Montreal (CEMTL), University of Montreal, Montreal, Quebec, Canada.

Adverse Events: None expected.

Conditions

Neuromuscular Blockade

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Group "N" for Standard reversal

Standard reversal of 50 µg.kg-1 neostigmine (up to a maximum dose of 5mg) and 7 µg.kg-1 glycopyrrolate at the end of surgery (when surgeons finish deep tissues closure) with starting TOF 1-3.

Group Type: ACTIVE_COMPARATOR

Neostigmine and glycopyrrolate

Intervention Type: DRUG

See arm descriptions

Group "S" for Sugammadex

Sugammadex 0.5 mg.kg-1 IV will be performed at the end of surgery (when surgeons finish deep tissues closure) with starting TOF 1-3.

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: DRUG

See arm descriptions

Interventions

Neostigmine and glycopyrrolate

See arm descriptions

Intervention Type: DRUG

Sugammadex

See arm descriptions

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• ASA 1-3 patients,
• Undergoing general anesthesia with rocuronium induced NMB,
• TOF 1-3 at the end of surgery,
• BMI < 36 kg.m-2,
• Age > 18 years old

Exclusion Criteria

• History of coronary artery disease and unstable before surgery
• History of serious cardiac arrhythmia (including atrial fibrillation)
• Renal or hepatic dysfunction
• Obstructive sleep apnea requiring continuous positive airway pressure (CPAP) machine
• Neuromuscular disease
• Allergy to any drug used in the study protocol

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ciusss de L'Est de l'Île de Montréal

OTHER

Sponsor Role: lead

Responsible Party

Philippe Richebe

Director of Research, Principal Investigator, Anesthesiologist, Associate Professor, MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Philippe PR Richebé, MD PhD

Role: PRINCIPAL_INVESTIGATOR

CIUSSS Est de l'île de Montréal

Locations

CIUSSS de l'Est de l'Ile de Montreal

Montreal, Quebec, Canada

Countries

Canada

Other Identifiers

2023-3091

Identifier Type: -

Identifier Source: org_study_id