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

• ClinicalTrials.gov Identifier: NCT03923556
• Recruitment Status: Recruiting
• First Posted: April 22, 2019
• Last Update Posted: February 12, 2021
• Sponsor: University of Colorado, Denver
• Information provided by (Responsible Party): University of Colorado, Denver

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Kidney Transplant; Complications; Postoperative Residual Curarization; Postoperative Residual Weakness	Drug: Sugammadex; Drug: Neostigmine	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: February 2, 2021
• Estimated Primary Completion Date: June 30, 2023
• Estimated Study Completion Date: September 30, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Sugammadex; Sugammadex	Drug: Sugammadex; Administration of Sugammadex 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
Active Comparator: Neostigmine; Neostigmine	Drug: Neostigmine; Administration of Neostigmine 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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Time from NMBR administration to adequate NMBR [ Time Frame: Within minutes from NMBR administration intraoperatively ]
   Intraoperative minutes from NMBR administration to qTOF T4/T1 equal or greater than 0.9
2. Time from NMBR administration to tracheal extubation [ Time Frame: Within minutes from NMBR administration intraoperatively ]
   Intraoperative minutes from NMBR administration to tracheal extubation
3. Duration of surgery [ Time Frame: During operating room stay ]
   Intraoperative minutes from surgical incision to closure (duration of surgery)
4. Duration of anesthesia [ Time Frame: During operating room stay ]
   Intraoperative minutes from tracheal intubation to tracheal extubation (duration of anesthesia)
5. Presence of qTOF <0.9 in PACU [ Time Frame: Within up to 3 hours after the end of surgery ]
   Incidence of qTOF <0.9 in PACU
6. Number of events of hypoventilation in PACU [ Time Frame: Within up to 3 hours after the end of surgery ]
   Number of events of hypoventilation lasting 1 minute or longer in PACU
7. Accumulated minutes of hypoventilation in PACU [ Time Frame: Within up to 3 hours after the end of surgery ]
   Accumulated minutes of hypoventilation in PACU
8. Delayed postoperative hypoventilation [ Time Frame: Within up to 3 postoperative days, counting from PACU discharge ]
   Presence of one or more episodes of hypoventilation in postoperative floor, adjusted to qTOF and other confounders
9. Number of events of delayed postoperative hypoventilation [ Time Frame: Within up to 3 postoperative days, counting from PACU discharge ]
   Number of events of hypoventilation lasting 1 minute or longer in the postoperative floor
10. Accumulated minutes of delayed postoperative hypoventilation [ Time Frame: Within up to 3 postoperative days, counting from PACU discharge ]
    Accumulated minutes of hypoventilation in the postoperative floor
11. qTOF <0.9 in postoperative floor [ Time Frame: Within up to 3 postoperative days, counting from PACU discharge ]
    Delayed detection of qTOF <0.9 in postoperative floor
12. Presence of postoperative pulmonary complications [ Time Frame: Within up to 3 postoperative days and at 14 +/- 3 days after surgery ]
    Presence of predefined postoperative pulmonary complications, including respiratory failure, reintubation, ARDS, pneumonia, pneumothorax, atelectasis, pleural effusion or bronchospasm.
13. Dyspnea functional limitation [ Time Frame: Within up to 14 +/- 3 days after surgery ]
    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)
14. Kidney graft function as measured by postoperative plasma clearance of creatinine (ClCr) [ Time Frame: Within up to 3 postoperative days and at 14 +/- 3 days after surgery ]
    Predefined kidney graft function based on postoperative ClCr
15. Number of participants with kidney graft dysfunction [ Time Frame: Within up to 3 postoperative days and at 14 +/- 3 days after surgery ]
    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.
16. Rate of adverse events [ Time Frame: Within up to 3 postoperative days ]
    Adverse events related to NMBR medications, including hypersensitivity and any other adverse events
17. Hospital resources utilization: total operating room time [ Time Frame: During operating room stay ]
    Hospital resources utilization parameters, including total operating room time
18. Hospital resources utilization: PACU stay duration [ Time Frame: During PACU stay ]
    Hospital resources utilization parameters, including total PACU stay duration
19. Hospital resources utilization: Hospital length of stay [ Time Frame: Within up to 14 +/- 3 days after surgery ]
    Hospital resources utilization parameters, including total hospital stay duration
20. Hospital resources utilization: Rate of ICU admission [ Time Frame: Within up to 14 +/- 3 days after surgery ]
    Hospital resources utilization parameters, including the need of ICU admission
21. Hospital resources utilization: ICU length of stay [ Time Frame: Within up to 14 +/- 3 days after surgery ]
    Hospital resources utilization parameters, including total ICU stay duration

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Ana Fernandez-Bustamante, M.D., Ph.D.; 303-724-2935; ana.fernandez-bustamante@cuanschutz.edu

Locations

United States, Colorado

University of Colorado Hospital; Recruiting

Aurora, Colorado, United States, 80045

Contact: Ana Fernandez-Bustamante, MD, PhD 303-724-2935

Sponsors and Collaborators

University of Colorado, Denver

Investigators

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

More Information

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT03923556
• Other Study ID Numbers: 18-2707
• First Posted: April 22, 2019
• Last Update Posted: February 12, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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:

Delayed Emergence from Anesthesia; Postoperative Complications; Pathologic Processes; Neostigmine; Cholinesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Parasympathomimetics; Autonomic Agents; Peripheral Nervous System Agents