The Use of Sugammadex in the Critically Ill

Recovery From Optimal Neuromuscular Blockade in the Critically Ill: Randomized Control Trial

Moderate and Deep neuromuscular blockade (rocuronium administered to a train of four count 0 and post-tetanic count of 1-2) in critically ill patients needing intubation or procedures can be reversed immediately and effectively by sugammadex avoiding unnecessary paralysis in an already weakened population

Study Overview

• Status: Unknown
• Conditions: Critical Illness
• Intervention / Treatment: Drug: Neostigmine; Drug: Rocuronium; Drug: Glycopyrrolate; Drug: Sugammadex

Detailed Description

The Critically ill is a special population needing immediate and aggressive treatments and interventions. Neuromuscular blockade is frequently used to secure an airway, optimize ventilation/oxygenation in ARDS, aid in maintaining hypothermia in patients post-cardiac arrest. Muscle relaxants can also contribute to neuromuscular weakness in the critically ill which can be a devastating condition. Appropriate depth of neuromuscular blockade is important but unnecessary paralysis need to be avoided. Rocuronium is one of the most popular neuromuscular blockade agents used in the critically ill (1). Sugammadex is a modified γ-cyclodextrin that reverses the effect of the steroidal nondepolarizing neuromuscular blocking agents rocuronium and vecuronium (2). Sugammadex results in rapid, predictable recovery from moderate and deep neuromuscular blockade. Sugammadex has been mostly studied and used in the surgical population but its use outside the operating room is still very relevant. The investigators set up to evaluate the potential benefit that may result from the reversal of NMB with sugammadex compared to neostigmine.

Objectives

In critically ill patients undergoing intubation receiving appropriate depth of NMB (moderate and deep blockade) the investigators will assess:

Primary objective:

1. To determine if choice of reversal agent affects time from intubation to return of a train of four (TOF) count of 1, and, separately, to return of a TOF ratio >0.9

Secondary objectives:

1. To document the ability of 1.0 mg/kg rocuronium (maximum 100 mg) to achieve satisfactory intubation conditions in the ICU, based on measurement of the number of intubation attempts and intubation grades in the entire cohort
2. To document General adverse effects: Hemodynamic instability, need for vasopressors etc

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Roupen Hatzakorzian, MD MSc; Phone Number: 31104 514 934 1934; Email: roupenhatz@hotmail.com

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • Recruiting
      • McGill University Health center
      • Contact: Roupen Hatzakorzian, MD, MSc; Phone Number: 34880 514 934 1934; Email: roupenhatz@hotmail.com
      • Principal Investigator: Roupen Hatzakorzian, MD, MSc
    • Montréal, Quebec, Canada, H4A 3J1
      • Recruiting
      • MUHC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients requiring intubation in the intensive care unit

Exclusion Criteria:

• Patients younger than 18 yr, to have known or suspected neuromuscular disease, allergies to medications to be used during intubation, a (family) history of malignant hyperthermia or severe renal insufficiency (glomerular filtration rate <30 ml/h) will not be eligible.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Neostigmine; Will receive rocuronium and neostigmine (5-70microg/kg) + glycopyrrolate (10microg/kg) at train of four 1	Drug: Neostigmine; the reversal of neuromuscular blockade with sugammadex compared to neostigmine.; Other Names: Prostigmin; Drug: Rocuronium; Both groups will receive rocuronium for paralysis during intubation; Other Names: Zemuron; Drug: Glycopyrrolate; The reversal of neuromuscular blockade with sugammadex compared to neostigmine/glycopyrrolate; Other Names: Robinul
Active Comparator: Sugammadex; Will receive rocuronium and sugammadex (4mg/kg) after a successful intubation (ETT is in the trachea and secure).	Drug: Rocuronium; Both groups will receive rocuronium for paralysis during intubation; Other Names: Zemuron; Drug: Sugammadex; the reversal of neuromuscular blockade with sugammadex compared to neostigmine.; Other Names: Bridion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Train of four ratio >0.9	time from intubation to return of a train of four (TOF) count of 1, and, separately, to return of a TOF ratio >0.9	up to 12 weeks

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Investigators: Principal Investigator: Roupen Hatzakorzian, MD MSc, McGill University Health Centre/Research Institute of the McGill University Health Centre

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2019
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): July 1, 2021

Study Registration Dates

• First Submitted: December 18, 2018
• First Submitted That Met QC Criteria: December 31, 2018
• First Posted (Actual): January 3, 2019

Study Record Updates

• Last Update Posted (Actual): August 21, 2019
• Last Update Submitted That Met QC Criteria: August 19, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: critically ill; rocuronium; sugammadex
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Enzyme Inhibitors; Adjuvants, Anesthesia; Neuromuscular Agents; Cholinesterase Inhibitors; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Parasympathomimetics; Glycopyrrolate; Rocuronium; Neostigmine
• Other Study ID Numbers: 2019-4576

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No