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Speed of Recovery of Reversal of Neuromuscular Blockade in Geriatric Patients Undergoing Spine Surgery

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ClinicalTrials.gov Identifier: NCT03112993
Recruitment Status : Completed
First Posted : April 13, 2017
Last Update Posted : August 16, 2018
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Boris Mraovic, University of Missouri-Columbia

Brief Summary:
Spine surgery is one of the most common operative procedures in the United States. It is performed in the prone position (a patient laying on belly). Muscle relaxants are given for neuromuscular blockade often referred as paralysis for surgical exposure which is maintained until the patient is returned to the supine position (a patient laying on back) at the end of surgery. At the end of the surgery the paralysis is reversed with a drug (neostigmine). A new drug (sugammadex) has the ability to rapidly reverse the paralysis but it is not well investigated in elderly. This study will investigate speed of recovery and complications of the two reversal drugs in elderly patients (age ≥ 65 years) undergoing posterior spine surgery.

Condition or disease Intervention/treatment Phase
Spine Surgery Drug: sugammadex Drug: Neostigmine Phase 4

Detailed Description:

The elderly (age ≥ 65 years) population is the fastest growing segment of the American population. Spine surgery is one of the most common operative procedures in the United States and, as the population ages, a larger percentage of geriatric patients will require this procedure. In addition, spinal surgery is often more complex in the elderly population, resulting in longer surgical times. A previous study reported that the rate of complex procedures increased 15-fold in Medicare recipients. Spine surgery is performed in the prone position and neuromuscular blockade (NMB) is maintained until the patient is returned to the supine position at the end of surgery to avoid the risk of patient movement, injury, and inadvertent tracheal extubation while prone. Currently, NMB is reversed with neostigmine immediately after turning the patients back to the supine position at the end of the procedure.

Rocuronium bromide, an intermediate-acting neuromuscular blocking agent (NMBA), is used in approximately 60% of surgical cases in the United States and is commonly used for muscle relaxation during spinal surgery. With aging, the clearance and half-life of rocuronium is prolonged resulting in a wide variability in the duration of action and time to reversal. Until recently, the only medication available for the reversal of neuromuscular blockade was neostigmine and postoperative residual neuromuscular block (PRNB) was common, especially in elderly patients. A recent study reported that PRNB occurred in 58% of elderly patients who were maintained at a moderate level (2 twitches in the TOF) of muscle relaxation with rocuronium during elective surgery. As a result, these older adults experienced an increased incidence of airway obstruction, hypoxemic events, muscle weakness, postoperative pulmonary complications, and increased PACU and hospital lengths of stay.

A new neuromuscular reversal agent sugammadex (Bridion®) has the ability to rapidly reverse both moderate and deep rocuronium-induced NMB. Another study reported that the mean time to complete reversal (TOF ratio ≥ 0.9) of a moderate block (2 twitches in the TOF) with sugammadex in geriatric patients was 2.9 minutes, which was only 1 minute longer than in younger patients. Reversal of NMB with neostigmine is much slower and it is reported to take approximately 19 minutes to achieve complete reversal in middle-aged patients. There is little available data on the NMB reversal time in older adults, but it will likely be even longer because the age-related physiologic changes prolong neuromuscular recovery. Thus, sugammadex has the potential to more rapidly reverse NMB in geriatric patients at the end of surgery. As a result, the use of sugammadex should decrease time in the OR and possibly PACU time and result in cost savings.

Neostigmine has cardiac muscarinic effects and, therefore, has to be administered with an anticholinergic agent such as glycopyrrolate to counteract these effects. A previous study found a 16% incidence of cardiac dysrhythmias in elderly patients who received neostigmine/glycopyrrolate NMB reversal. The ability of sugammadex to completely reverse NMB without the addition of an anticholinesterase agent should result in an improved safety profile in elderly patients.

The goal of this prospective, randomized, double-blinded controlled trial is to test the hypothesis that the reversal of neuromuscular blockage with sugammadex as compared to neostigmine in geriatric patients will provide a shorter time to complete recovery of neuromuscular function, improve the workflow in the operating room and decrease operative costs.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants will receive (per a randomization schedule) either sugammadex, or neostigmine/glycopyrrolate to reverse neuromuscular blockade at the end of the surgery. The reversal agent will be prepared in a blinded fashion.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The surgeon, anesthesiologist, operating room staff, patients, personnel in the postanesthesia care unit (PACU) as well as the investigators collecting the postoperative data will be blinded to the group allocation.
Primary Purpose: Treatment
Official Title: A Prospective, Randomized, Double-Blind Clinical Trial Evaluating the Speed of Recovery and Safety of Reversal of Neuromuscular Blockade With Sugammadex (Bridion™) Versus Neostigmine in Geriatric Patients Undergoing Spine Surgery
Actual Study Start Date : May 30, 2017
Actual Primary Completion Date : August 13, 2018
Actual Study Completion Date : August 14, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Sugammadex group
2 mg/kg of sugammadex, IV once at the end of the surgery. Dosing will be based on actual body weight not ideal body weight.
Drug: sugammadex
once at the end of the surgery
Other Name: Bridion

Active Comparator: Neostigmine group

50 micrograms/kg (not to exceed 5 mg) and glycopyrrolate, 10 micrograms/kg (not to exceed 1 mg), IV once at the end of the surgery.

Dosing will be based on actual body weight not ideal body weight.

Drug: Neostigmine
once at the end of the surgery




Primary Outcome Measures :
  1. Difference in time of neuromuscular recovery from a neuromuscular moderate blockade [ Time Frame: Day 1 ]
    Speed of neuromuscular recovery in seconds measured by recovery of the T4:T1 ratio ≥ 0.9 (measured with a TOF-watch)


Secondary Outcome Measures :
  1. Difference in time from neuromuscular reversal to tracheal extubation [ Time Frame: Day 1 ]
    measured in seconds

  2. Difference in time from neuromuscular reversal to exit from OR [ Time Frame: Day 1 ]
    measured in seconds

  3. Number of participants with hemodynamic instability related to neuromuscular reversal agent [ Time Frame: Baseline, Day 1 ]
    Blood pressure, blood oxygen saturation, cardiac dysrhythmia, heart rate > 100 beats per minute or < 60 beats per minute, or increase or decrease of ≥20% in heart rate from the baseline heart rate, EKG

  4. Difference in Visual Analog Score (VAS) [ Time Frame: Day 1 ]
    VAS score for nausea and pain during stay in Post anesthesia Care Unit (PACU)

  5. Difference in length of stay in PACU [ Time Frame: Day 1 ]
    Length of PACU stay measured in minutes


Other Outcome Measures:
  1. Difference in time to first ambulation after surgery [ Time Frame: From Day 1 up to 1 week, depending on individual recovery time ]
    time from end of anesthesia to the first ambulation in minutes

  2. Difference in postoperative patient satisfaction scores [ Time Frame: Day 1 ]
    perioperative questionnaire developed by Bauer et al



Information from the National Library of Medicine

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Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Posterior spinal surgery
  2. Age ≥ 65 years
  3. American Society of Anesthesiologists (ASA) grade I-III

Exclusion Criteria:

  1. Inability to obtain written informed consent
  2. Allergy to rocuronium or anesthetic agents used in the protocol
  3. Known or suspected neuromuscular disorders
  4. Significant renal disease with a serum creatinine ≥ 2 mg/dl
  5. Significant liver disease
  6. A family history of malignant hyperthermia

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03112993


Locations
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United States, Missouri
University on Missouri Hospital
Columbia, Missouri, United States, 65212
Sponsors and Collaborators
University of Missouri-Columbia
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Boris Mraovic, MD Univesity of Missouri-Columbia

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Responsible Party: Boris Mraovic, Associate Professor, University of Missouri-Columbia
ClinicalTrials.gov Identifier: NCT03112993     History of Changes
Other Study ID Numbers: IRB # 2008066
MISP # 56051. ( Other Grant/Funding Number: Merck & Co. )
First Posted: April 13, 2017    Key Record Dates
Last Update Posted: August 16, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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.: No
Keywords provided by Boris Mraovic, University of Missouri-Columbia:
spine surgery
neuromuscular blockade
sugammadex
elderly
reversal
neostigmine
recovery
Additional relevant MeSH terms:
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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