Clinical trial

The Use of Sugammadex as Rescue Therapy Following Inadequate Reversal With Neostigmine

Name

STUDY00004369

Description

Neuromuscular blocking agents (NMBAs) are commonly used in the practice of anesthesiology for skeletal muscle relaxation to facilitate tracheal intubation, mechanical ventilation, and to provide optimal surgical conditions. In order to prevent residual NMB, it is vital to adequately reverse any use of a non-depolarizing NMBA. This was historically done using an anticholinesterase such as neostigmine, which would increase the concentration of acetylcholine at the neuromuscular junction leading to the return of neuromuscular transmission. Unfortunately, there are disadvantages to the use of an anticholinesterase. It was in this context that sugammadex was found to be a valuable addition to the anesthesiologist's armamentarium. It is a modified γ-cyclodextrin that encapsulates the aminosteroid NMBAs rocuronium and vecuronium. This project is a double-blind randomized placebo-controlled dose-response trial that aims to determine the time taken to achieve adequate reversal comparing five doses of sugammadex as rescue therapy following inadequate reversal with neostigmine. The study team will recruit patients aged 18 years and above from the main operating room and outpatient surgery center at Grady Memorial Hospital who are undergoing elective surgery under general anesthesia, who has received NMB, received neostigmine for NMB reversal, and achieved a TOF count ≥ 3 twitches but not a TOF ratio of 0.9 fifteen minutes after neostigmine was given. Those with a TOF count \< 3 twitches will drop out of the study as there are already specified doses of sugammadex for that level of NMB

Trial arms

Trial start

2023-07-21

Estimated PCD

2024-07-01

Trial end

2024-07-01

Status

Recruiting

Phase

Early phase I

Treatment

Sugammadex

Sugammadex is a FDA-approved drug that is in routine clinical use for NMB reversal. Patients will be randomized to six groups: 2 mg/kg (the lowest dose approved by the FDA), 1 mg/kg, 0.5 mg/kg, 0.25 mg/kg, 0.125 mg/kg of sugammadex and placebo. Doses would be based on actual body weight. The time taken to reach a TOF ratio of 0.9 thereafter would be measured. If the patient fails to achieve this goal by 10 minutes, sugammadex would be given in 2 mg/kg increments until the patient reaches this threshold and can be safely extubated.

Arms:

Sugammadex 0.125 mg/kg, Sugammadex 0.25 mg/kg, Sugammadex 0.5 mg/kg, Sugammadex 1 mg/kg, Sugammadex 2 mg/kg

Placebo

Normal saline will be used as placebo. The inclusion of a placebo group would allow us to examine if patients may recover spontaneously over that time without needing any sugammadex at all, and what parameters may predict that subset of patients. It will also improve the dose response modelling, in that randomization has been weighted so that patients who are least likely to need sugammadex (i.e. if they achieved a TOF count of 4 twitches without fade) are more likely to be in the placebo group or at the lowest dose of sugammadex that is being tested.

Arms:

Placebo

Size

Primary endpoint

The time taken to achieve a TOF ratio of 0.9 after administration sugammadex

10 minutes post administration of study drug

Eligibility criteria

Inclusion Criteria: * Patients aged 18 years and above who will * Undergo an elective surgery in the main operating room or outpatient surgery center at Grady Memorial Hospital, * Receive general anesthesia (standardized to sevoflurane for maintenance), * Receive rocuronium for NMB, * Receive neostigmine for NMB reversal, * Achieve a TOF count of at least 3 twitches but not a TOF ratio of 0.9 fifteen minutes after neostigmine has been given, and * Able and willing to provide informed consent. Exclusion Criteria: * Pregnancy and/or lactating * BMI ≥ 40, * Severe renal impairment, i.e. chronic kidney disease stages IV and V as defined by GFR \< 30 ml/min/1.73 m2 * Severe hepatic impairment, i.e. Child-Pugh score C * Pre-existing neuromuscular disease, * Anticipated need for postoperative intubation, and/or * Known hypersensitivity reactions to rocuronium, neostigmine and/or sugammadex. * Adults unable to consent * Prisoners * Cognitively impaired or Individuals with Impaired Decision-Making Capacity * Individuals who are not able to clearly understand English

Protocol

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Updated at

2023-07-25

1 organization

1 product

1 drug

1 indication

Organization

Emory University

Product

Sugammadex

Indication

Neuromuscular Blockade

Drug

Varlilumab