The Use of Sugammadex in the Critically Ill

• ClinicalTrials.gov Identifier: NCT03791801
• Recruitment Status: Unknown
• First Posted: January 3, 2019
• Last Update Posted: August 21, 2019
• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Information provided by (Responsible Party): Roupen Hatzakorzian, MD, McGill University Health Centre/Research Institute of the McGill University Health Centre

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Critical Illness	Drug: Sugammadex; Drug: Neostigmine; Drug: Rocuronium; Drug: Glycopyrrolate	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: RCT
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: Recovery From Optimal Neuromuscular Blockade in the Critically Ill: Randomized Control Trial
• Estimated Study Start Date: September 1, 2019
• Estimated Primary Completion Date: December 1, 2020
• Estimated Study Completion Date: July 1, 2021

Arms and Interventions

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 Name: Prostigmin; Drug: Rocuronium; Both groups will receive rocuronium for paralysis during intubation; Other Name: Zemuron; Drug: Glycopyrrolate; The reversal of neuromuscular blockade with sugammadex compared to neostigmine/glycopyrrolate; Other Name: Robinul
Active Comparator: Sugammadex; Will receive rocuronium and sugammadex (4mg/kg) after a successful intubation (ETT is in the trachea and secure).	Drug: Sugammadex; the reversal of neuromuscular blockade with sugammadex compared to neostigmine.; Other Name: Bridion; Drug: Rocuronium; Both groups will receive rocuronium for paralysis during intubation; Other Name: Zemuron

Outcome Measures

Primary Outcome Measures :

1. Train of four ratio >0.9 [ Time Frame: up to 12 weeks ]
   time from intubation to return of a train of four (TOF) count of 1, and, separately, to return of a TOF ratio >0.9

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Roupen Hatzakorzian, MD MSc; 514 934 1934 ext 31104; roupenhatz@hotmail.com

Locations

Canada, Quebec

McGill University Health Center; Recruiting

Montreal, Quebec, Canada, H3A 1A1

Contact: Roupen Hatzakorzian, MD, MSc 514 934 1934 ext 34880 roupenhatz@hotmail.com

Principal Investigator: Roupen Hatzakorzian, MD, MSc

MUHC; Recruiting

Montréal, Quebec, Canada, H4A 3J1

Sponsors and Collaborators

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

More Information

• Responsible Party: Roupen Hatzakorzian, MD, Principal Investigator, McGill University Health Centre/Research Institute of the McGill University Health Centre
• ClinicalTrials.gov Identifier: NCT03791801
• Other Study ID Numbers: 2019-4576
• First Posted: January 3, 2019
• Last Update Posted: August 21, 2019
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Roupen Hatzakorzian, MD, McGill University Health Centre/Research Institute of the McGill University Health Centre:

sugammadex; rocuronium; critically ill

Additional relevant MeSH terms:

Critical Illness; Disease Attributes; Pathologic Processes; Glycopyrrolate; Rocuronium; Neostigmine; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Neuromuscular Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Cholinesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Parasympathomimetics; Autonomic Agents; Adjuvants, Anesthesia; Muscarinic Antagonists; Cholinergic Antagonists