Sugammadex Versus Neostigmine for Reversal of Neuromuscular Blockade at the End of Kidney Transplantation Surgery

A Double-blind, Randomized, Parallel Study to Compare the Efficacy of Sugammadex Versus Neostigmine for Reversal of Neuromuscular Blockade at the End of Kidney Transplantation Surgery in Patients With Severe Kidney Dysfunction

The purpose of this study is to compare two medications that reverse muscle paralysis at the end of kidney transplant surgery with the goal of reducing residual muscle weakness and insufficient respiratory function after surgery.

Study Overview

• Status: Recruiting
• Conditions: Postoperative Residual Curarization; Kidney Transplant; Complications; Postoperative Residual Weakness
• Intervention / Treatment: Drug: Sugammadex; Drug: Neostigmine

Detailed Description

This is a prospective randomized double-blind single center study on patients with severe kidney failure undergoing kidney transplantation surgery. Patients will have their muscles paralyzed during general anesthesia for surgery. At the end of surgery, muscle paralysis will be reversed with either neostigmine (control group) or sugammadex (intervention group). Residual muscle weakness and respiratory function will be monitored after surgery with a quantitative train-of-four (qTOF) monitor and a noninvasive continuous ventilation monitor. The investigators hypothesize that patients receiving sugammadex will have less residual muscle weakness and better respiratory function than patients receiving neostigmine. Respiratory and kidney function parameters and any adverse events will be collected during the hospital stay. Patients will contacted for a study follow up around 2 weeks after their surgery.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ana Fernandez-Bustamante, M.D., Ph.D.; Phone Number: 303-724-2935; Email: ana.fernandez-bustamante@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Hospital
      • Contact: Ana Fernandez-Bustamante, MD, PhD; Phone Number: 303-724-2935

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• At least 18 years or older
• Diagnosed with severe kidney dysfunction (defined by plasma creatinine clearance <30 mL/min)
• Planning on kidney transplantation surgery at the University of Colorado Hospital.

Exclusion Criteria:

• Patients unable to sign the informed consent
• Pregnant women
• Body Mass Index (BMI) > 40 kg/m2
• Pre-existing oxygen or ventilatory dependency (24h use of oxygen or other noninvasive or invasive ventilatory support)
• Patients with any pulmonary, neuromuscular or other disease that severely limits their respiratory functional status (e.g. unable to achieve 4 Metabolic Equivalent of Tasks, METs, such as climbing up 1 flight of stairs)
• Presence of any contraindication for any of the study-related medications or interventions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sugammadex	Drug: Sugammadex; Administration of Sugammadex intravenously at a dose appropriate for the reversal of neuromuscular blockade (usually 2-4 mg/kg) at the end of the surgery before tracheal extubation
Active Comparator: Neostigmine	Drug: Neostigmine; Administration of Neostigmine intravenously at a dose appropriate for the reversal of neuromuscular blockade (usually 0.03-0.07 mg/kg) at the end of the surgery before tracheal extubation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypoventilation in post-anesthesia care unit (PACU)	Presence of one or more episodes of hypoventilation in PACU, adjusted to qTOF and other confounders	Within up to 3 hours after the end of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from NMBR administration to adequate NMBR	Intraoperative minutes from NMBR administration to qTOF T4/T1 equal or greater than 0.9	Within minutes from NMBR administration intraoperatively
Time from NMBR administration to tracheal extubation	Intraoperative minutes from NMBR administration to tracheal extubation	Within minutes from NMBR administration intraoperatively
Duration of surgery	Intraoperative minutes from surgical incision to closure (duration of surgery)	During operating room stay
Duration of anesthesia	Intraoperative minutes from tracheal intubation to tracheal extubation (duration of anesthesia)	During operating room stay
Presence of qTOF <0.9 in PACU	Incidence of qTOF <0.9 in PACU	Within up to 3 hours after the end of surgery
Number of events of hypoventilation in PACU	Number of events of hypoventilation lasting 1 minute or longer in PACU	Within up to 3 hours after the end of surgery
Accumulated minutes of hypoventilation in PACU	Accumulated minutes of hypoventilation in PACU	Within up to 3 hours after the end of surgery
Delayed postoperative hypoventilation	Presence of one or more episodes of hypoventilation in postoperative floor, adjusted to qTOF and other confounders	Within up to 3 postoperative days, counting from PACU discharge
Number of events of delayed postoperative hypoventilation	Number of events of hypoventilation lasting 1 minute or longer in the postoperative floor	Within up to 3 postoperative days, counting from PACU discharge
Accumulated minutes of delayed postoperative hypoventilation	Accumulated minutes of hypoventilation in the postoperative floor	Within up to 3 postoperative days, counting from PACU discharge
qTOF <0.9 in postoperative floor	Delayed detection of qTOF <0.9 in postoperative floor	Within up to 3 postoperative days, counting from PACU discharge
Presence of postoperative pulmonary complications	Presence of predefined postoperative pulmonary complications, including respiratory failure, reintubation, ARDS, pneumonia, pneumothorax, atelectasis, pleural effusion or bronchospasm.	Within up to 3 postoperative days and at 14 +/- 3 days after surgery
Dyspnea functional limitation	Score on standardized Patient-Reported Outcomes Measurement Information System (Promis) dyspnea functional limitation questionnaire score, compared to patient's baseline. Functional measurements include walking, lifting and activities of daily living. The higher the score on this instrument the more functional limitation (scale range is from 0 to 30)	Within up to 14 +/- 3 days after surgery
Kidney graft function as measured by postoperative plasma clearance of creatinine (ClCr)	Predefined kidney graft function based on postoperative ClCr	Within up to 3 postoperative days and at 14 +/- 3 days after surgery
Number of participants with kidney graft dysfunction	Predefined kidney graft negative outcomes including: postoperative increasing ClCr, reduced daily urine output, need for dialysis postoperatively, and/or diagnosis of delayed graft function or kidney graft rejection.	Within up to 3 postoperative days and at 14 +/- 3 days after surgery
Rate of adverse events	Adverse events related to NMBR medications, including hypersensitivity and any other adverse events	Within up to 3 postoperative days
Hospital resources utilization: total operating room time	Hospital resources utilization parameters, including total operating room time	During operating room stay
Hospital resources utilization: PACU stay duration	Hospital resources utilization parameters, including total PACU stay duration	During PACU stay
Hospital resources utilization: Hospital length of stay	Hospital resources utilization parameters, including total hospital stay duration	Within up to 14 +/- 3 days after surgery
Hospital resources utilization: Rate of ICU admission	Hospital resources utilization parameters, including the need of ICU admission	Within up to 14 +/- 3 days after surgery
Hospital resources utilization: ICU length of stay	Hospital resources utilization parameters, including total ICU stay duration	Within up to 14 +/- 3 days after surgery

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Ana Fernandez-Bustamante, M.D., Ph.D., University of Colorado School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2021
• Primary Completion (Estimated): September 30, 2023
• Study Completion (Estimated): December 30, 2023

Study Registration Dates

• First Submitted: March 28, 2019
• First Submitted That Met QC Criteria: April 19, 2019
• First Posted (Actual): April 22, 2019

Study Record Updates

• Last Update Posted (Actual): August 23, 2023
• Last Update Submitted That Met QC Criteria: August 21, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Delayed Emergence from Anesthesia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Enzyme Inhibitors; Cholinesterase Inhibitors; Parasympathomimetics; Neostigmine
• Other Study ID Numbers: 18-2707

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes