Neuromuscular Blockade in Patients With Severe Renal Impairment

• ClinicalTrials.gov Identifier: NCT03904550
• Recruitment Status: Active, not recruiting
• First Posted: April 5, 2019
• Last Update Posted: January 12, 2023
• Sponsor: University of Texas Southwestern Medical Center
• Information provided by (Responsible Party): Tiffany B Moon, University of Texas Southwestern Medical Center

Study Description

Brief Summary:

This study is intended to be a single-site, prospective, randomized, double-blinded study that intends to enroll a total of 60 patients with severe renal impairment undergoing surgery with general endotracheal anesthesia at Parkland Hospital. Patients will be randomized to receive either neostigmine (for reversal of cisatracurium) or sugammadex (for reversal of rocuronium). A standardized anesthetic protocol that is usual and customary for the type of operation the patient is having will be provided to the anesthesia teams of enrolled subjects. The remainder of the anesthetic care of the subject will not deviate from the standard of care. All patients will be monitored with continuous pulse oximetry postoperatively for 24 hours.

Condition or disease	Intervention/treatment	Phase
Neuromuscular Blockade; Renal Impairment	Drug: Cisatracurium + Neostigmine; Drug: Rocuronium + Sugammadex	Phase 2

Detailed Description:

This will be a prospective, randomized, double-blinded study of surgical patients with severe renal impairment that seeks to address the following:

Specific Aim:

To determine whether rocuronium-induced moderate neuromuscular blockade and reversal with sugammadex achieves recovery of neuromuscular function (TOF ≥ 0.9) faster than reversal of cisatracurium-induced moderate neuromuscular blockade and reversal with neostigmine in patients with severe renal impairment.

Primary Hypothesis:

Patients with severe renal impairment who are reversed with sugammadex after rocuronium will achieve a TOF ≥0.9 within a time frame that is one-third of the time it takes for reversal with neostigmine after cisatracurium.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: single site, randomized, controlled
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: double blinded
• Primary Purpose: Treatment
• Official Title: Reversal of Neuromuscular Blockade in Patients With Severe Renal Impairment
• Actual Study Start Date: December 10, 2019
• Actual Primary Completion Date: August 11, 2022
• Estimated Study Completion Date: June 29, 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Cisatracurium + Neostigmine; Patients in the rocuronium/sugammadex group will receive 0.6 mg/kg of rocuronium for neuromuscular paralysis during induction. Additional rocuronium will be given to keep the patient at a neuromuscular depth of 1 twitch throughout the surgery until the last 30 minutes, during which the patient will be kept at 2 twitches.	Drug: Cisatracurium + Neostigmine; Maintenance neuromuscular blockade with boluses of cisatracurium to keep train-of-four (TOF) 1-2 twitches. For reversal, neostigmine with glycopyrrolate
Active Comparator: Rocuronium + Sugammadex; Patients in the cisatracurium/neostigmine group will receive 0.2 mg/kg of cisatracurium for neuromuscular paralysis during induction. Additional cisatracurium will be given to keep the patient at a neuromuscular depth of 1 twitch throughout the surgery until the last 30 minutes, during which the patient will be kept at 2 twitches.	Drug: Rocuronium + Sugammadex; Maintenance neuromuscular blockade with boluses of rocuronium to keep TOF 1-2 twitches. For reversal, sugammadex

Outcome Measures

Primary Outcome Measures :

1. Time until complete reversal of neuromuscular blockade [ Time Frame: In the operating room from induction to extubation. ]
   Measure how long it takes to return from a TOF of 2 to a TOF ≥ 0.9.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• 18-80 years old
• Severe renal impairment (CrCl < 30 mL/min)
• Undergoing non-emergent surgery that requires neuromuscular blockade
• Planned extubation in the operating room immediately after surgery
• American Society of Anesthesiologists (ASA) physical status classification 3 to 4
• Willing and able to consent in English or Spanish
• No personal history of neuromuscular disease

Exclusion Criteria:

• Age less than 18 or older than 80
• Patient does not speak English or Spanish
• Planned postoperative intubation/ventilation
• Allergy to sugammadex, neostigmine, glycopyrrolate, cisatracurium, or rocuronium
• Family or personal history of malignant hyperthermia
• Patient refusal
• Pregnant or nursing women
• "Stat" (emergent) cases
• Pre-existing muscle weakness of any etiology
• Patients on toremifene (a selective estrogen receptor modulator)
• Women on oral contraceptives who do not wish to use a non-hormonal method of contraception for 7 days following surgery

Contacts and Locations

Locations

United States, Texas

Parkland Health & Hospital System

Dallas, Texas, United States, 75390

Sponsors and Collaborators

University of Texas Southwestern Medical Center

Investigators

• Principal Investigator: Tiffany Moon, MD; University of Texas Southwestern Medical Center

More Information

• Responsible Party: Tiffany B Moon, ASSOC PROFESSOR, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT03904550
• Other Study ID Numbers: STU-2018-0411
• First Posted: April 5, 2019
• Last Update Posted: January 12, 2023
• Last Verified: January 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Rocuronium; Cisatracurium; 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