## Protocol Section
### Identification Module
**NCT ID:** NCT06436768

**Brief Title:** Efficacy and Safety of Sugammadex in Thoracoscopy Thymectomy for Chinese Adults With Myasthenia Gravis

**Official Title:** Effectiveness of Sugammadex Versus Neostigmine on the Reversal of Rocuronium-induced Neuromuscular Blockade in Patients With Myasthenia Gravis After Thoracoscopic Thymectomy: A Multicenter Randomized Controlled Trial

#### Organization Study ID Info
**ID:** TRRCKY202 l-009-GZ (2023)-003
#### Organization
**Class:** OTHER
**Full Name:** Beijing Tongren Hospital
#### Secondary ID Infos
**Domain:** Wu Jieping Medical Foundation
**ID:** 320.6750.2020-21-10
**Type:** OTHER_GRANT
### Status Module
#### Completion Date
**Date:** 2025-06-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-31

**Type:** ESTIMATED

**Last Update Submit Date:** 2024-05-24

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2024-10-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-31
**Type:** ESTIMATED
**Study First Submit Date:** 2024-05-14
**Study First Submit QC Date:** 2024-05-24
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** The First Affiliated Hospital with Nanjing Medical University

#### Lead Sponsor

**Class:** OTHER

**Name:** Beijing Tongren Hospital

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The purpose of this study was to demonstrate in patients with myasthenia gravis (MG) undergoing thoracoscopic thymectomy faster recovery from a moderate neuromuscular block induced by rocuronium after reversal at reappearance of T2 by 2.0 mg/kg sugammadex compared to 50 ug/kg neostigmine.

Methods: A total of 64 patients with MG undergoing thoracoscopic thymectomy will be randomly divided into two groups: Sugammadex group (S group) and Neostigmine group (N group). The same anesthesia methods will be applied in both groups. Patients of S group will receive a dose of 2.0 mg/kg sugammadex after the last dose of rocuronium, at reappearance of T2. Patients of N group will receive a dose of 50 ug/kg neostigmine after the last dose of rocuronium, at reappearance of T2. The primary endpoint is time from start of administration of sugammadex or neostigmine to recovery of train-of-four stimulation ratio (TOFr) to 0.9. Secondary end points include time from start of administration of sugammadex or neostigmine to recovery of TOFr to 0.8 and 0.7, time to extubation, clinical signs of neuromuscular recovery, hemodynamic changes after muscle relaxation antagonism, adverse effects, time to operating room (OR) discharge, time to post-anesthesia care unit (PACU) discharge, and pulmonary complications within 7 days after the operation.

**Detailed Description:** Due to neuromuscular transmission and functioning deficits, patients with myasthenia gravis (MG) are at increased risk of postoperative residual curarization (PORC), and may even develop into postoperative myasthenia crisis (PMC), which is a serious complication after thymectomy and increases the risk of death, with an incidence of up to 18.2%.

Effective reversal of neuromuscular blockade is crucial to ensure patient safety, reduce the incidence of PORC or PMC and prompt postoperative recovery. Traditionally, neostigmine, an acetylcholinesterase inhibitor, can be employed for neuromuscular blocking agent (NMBA) reversal. However, neostigmine is associated with potential drawbacks, such as delayed recovery and adverse muscarinic side effects.

Sugammadex, a selective relaxant binding agent, represents a relatively new alternative for NMBA reversal, specifically designed to encapsulate and inactivate aminosteroid NMBAs. The clinical benefits of sugammadex have been documented in several studies, demonstrating faster reversal of neuromuscular blockade and more predictable recovery profiles compared to neostigmine. However, the use of sugammadex in patients with MG remains an area of limited evidence. To date, to the best of our knowledge, there is a lack of prospective research to elucidate the application value of sugammadex in thymectomy in patients with MG.

This study is a prospective randomized controlled trial aimed at exploring the efficacy and safety of sugammadex compared to neostigmine for the reversal of neuromuscular blockade in patients with myasthenia gravis after thoracoscopic thymectomy.

### Conditions Module

**Conditions:**

- Reversal of Neuromuscular Blockade

**Keywords:**

- neuromuscular blockade

- Sugammadex

- Neostigmine

- Myasthenia gravis

- Postoperative Residual Curarization

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** Randomized parallel controlled trial

##### Masking Info

**Masking:** TRIPLE

**Masking Description:** The doctors making the follow-up assessment were unaware of the treatment received, and none of the doctors who administered the injections carried out the follow- up evaluations. Thus, both the patients and the assessing doctors were remained unaware of the treatment received throughout the trial

**Who Masked:**

- PARTICIPANT

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 64

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** After the last dose of rocuronium, at reappearance of T2, a dose of 2.0 mg/kg sugammadex was administered.

**Intervention Names:**

- Drug: Sugammadex

**Label:** Sugammadex group (S group)

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** After the last dose of rocuronium, at reappearance of T2, a dose of 50 ug/kg neostigmine plus atropine 0.02 mg/kg was administered.

**Intervention Names:**

- Drug: Neostigmine

**Label:** Neostigmine group (N group)

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Sugammadex group (S group)

**Description:** After the last dose of rocuronium, at reappearance of T2, a dose of 2.0 mg/kg sugammadex was administered.

Dose will be according to participant actual body weight.

**Name:** Sugammadex

**Other Names:**

- S group

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Neostigmine group (N group)

**Description:** After the last dose of rocuronium, at reappearance of T2, a dose of 50 ug/kg neostigmine (up to 5 mg maximum dose) plus atropine 0.02 mg/kg (up to 2 mg maximum dose) was administered.

Dose will be according to participant actual body weight.

**Name:** Neostigmine

**Other Names:**

- N group

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** The comparison of the recovery periods between groups when the start of administering reversal agent to the recovery of TOF ratio≥ 0.9

**Measure:** Recovery time

**Time Frame:** After operation within 24 hours

#### Secondary Outcomes

**Description:** Muscle relaxation monitoring was performed with an accelero-myography (AMG) neuromuscular monitor by assessment of the TOF responses of adductor pollicis muscle to ulnar nerve stimulation every 15 seconds. T1 and T4 refer to the amplitudes of the first and fourth twitches, respectively, after TOF nerve stimulation. The TOFr, that is T4/T1 Ratio (expressed as a decimal of up to 1.0) represents the extent of recovery from neuromuscular blockade (NMB). A faster time to TOFr 0.8 indicates a faster recovery from NMB.

**Measure:** Time from start of administration of sugammadex or neostigmine to the train-of-four stimulation ratio (TOFr) 0.8

**Time Frame:** After operation within 120 minutes

**Description:** Muscle relaxation monitoring was performed with an accelero-myography (AMG) neuromuscular monitor by assessment of the TOF responses of adductor pollicis muscle to ulnar nerve stimulation every 15 seconds. T1 and T4 refer to the amplitudes of the first and fourth twitches, respectively, after TOF nerve stimulation. The TOFr, that is T4/T1 Ratio (expressed as a decimal of up to 1.0) represents the extent of recovery from neuromuscular blockade (NMB). A faster time to TOFr 0.7 indicates a faster recovery from NMB.

**Measure:** Time from start of administration of sugammadex or neostigmine to the train-of-four stimulation ratio (TOFr) 0.7.

**Time Frame:** After operation within 120 minutes

**Description:** The time period between administering a reversal agent to extubation

**Measure:** Extubation time

**Time Frame:** After operation within 60 minutes

**Description:** The time period between administering a reversal agent to operating room discharge

**Measure:** Time to discharge from the operating room

**Time Frame:** After operation within 60 minutes

**Description:** The time period between entering the recovery room amd discharge from recovery room

**Measure:** Time to discharge from recovery room

**Time Frame:** After operation within 120 minutes

**Description:** Incidence of postoperative residual neuromuscular blockade (rNMB) (defined as a train-of-four ratio, TOFR \<0.9) measured 30 min after administration of the reversal agent.

**Measure:** Incidence of postoperative residual neuromuscular blockade (rNMB)

**Time Frame:** After operation within 24 hours

**Description:** Unit: %; This value is a percentage. Any adverse effects in the operating room or in PACU include procedural pain, nausea, vomiting, dizziness, pruritus, reintubation, incision site complication, postprocedural nausea, vomiting, flatulence, procedural complication, insomnia, muscular weakness, headache, pharyngolaryngeal pain.

**Measure:** The incidence of adverse effects

**Time Frame:** Within 48 hours after operation

**Description:** After extubation to prior to discharge from the recovery room, record the number of patients who need rescue medication because of clinical signs of residual paralysis (i.e. if a patient complain about muscle weakness, difficulty breathing, or oxygen desaturation ≤ 95%)

**Measure:** Number of patients who need rescue medication

**Time Frame:** After operation within 24 hours

**Description:** The proportion of patients in this group who experience mean arterial blood pressure fluctuation ≥ 20% within 30 minutes after administration of antagonists compared with before administration of antagonists

**Measure:** The incidence of mean arterial blood pressure fluctuations ≥20%

**Time Frame:** After operation within 24 hours

**Description:** The proportion of patients in this group who experience heart rate fluctuation ≥ 20% within 30 minutes after administration of antagonists compared with before administration of antagonists

**Measure:** The incidence of heart rate fluctuations ≥20%

**Time Frame:** After operation within 24 hours

**Description:** Unit: %; This value is a percentage. Postoperative pulmonary complications include pneumonia; aspiration pneumonitis; atelectasis; respiratory failure; bronchospasm; pulmonary congestion; pleural effusion; pneumothorax.

**Measure:** The incidence of postoperative pulmonary complications

**Time Frame:** Within the first 7 days after surgery

**Description:** Unit: %; This value is a percentage.

**Measure:** Unplanned ICU hospitalization rate

**Time Frame:** 1 months after operation

**Description:** Blood oxygenation values will be measured using pulse oximetry from the time of PACU admission until discharge from the PACU

**Measure:** Hypoxemic events

**Time Frame:** participants will be followed for the duration of the PACU stay, an expected average of 2 hours, up to 7 days

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* • Patients with MG scheduled for elective thoracoscopic thymectomy

  * Aged 18 to 65 years
  * American society of Anesthesiologists (ASA) physical status classification system: I - III

Exclusion Criteria:

* Inability to obtain written informed consent
* With severe renal or hepatic dysfunction
* A plan to return to ICU with intubation postoperation
* A family history of malignant hyperthermia
* Suspected difficult airway
* Allergy to medications involved in the study
* A contraindication for neostigmine or sugammadex administration
* The patient's arm is not available for neuromuscular monitoring
* Patients receiving medication known to interfere with NMBAs (e.g., anticonvulsants, antibiotics, magnesium salts)
* Pregnant or lactating patients

**Maximum Age:** 65 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** xueliangchunhuayi@163.com

**Name:** Chunhua Hu

**Phone:** 0086-18310454243

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Beijing

**Contacts:**

***Contact 1:***

- **Email:** xueliangchunhuayi@163.com

- **Name:** Chunhua Hu

- **Phone:** 0086-18310454243

- **Role:** CONTACT

**Country:** China

**Facility:** Beijing tongren Hospital, Capital Medical University

**State:** Beijing

**Zip:** 100000

**Location 2:**

**City:** Nanjing

**Contacts:**

***Contact 1:***

- **Email:** liushijiang@njmu.edu.com

- **Name:** Shijiang Liu

- **Phone:** 0086-13814001801

- **Role:** CONTACT

**Country:** China

**Facility:** The First Affiliated Hospital with Nanjing Medical University

**State:** Jiangsu

**Zip:** 210000

#### Overall Officials

**Official 1:**

**Affiliation:** Beijing Tongren Hospital

**Name:** Guyan Wang

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Cata JP, Lasala JD, Williams W, Mena GE. Myasthenia Gravis and Thymoma Surgery: A Clinical Update for the Cardiothoracic Anesthesiologist. J Cardiothorac Vasc Anesth. 2019 Sep;33(9):2537-2545. doi: 10.1053/j.jvca.2018.07.036. Epub 2018 Jul 29.

**PMID:** 30219643

**Citation:** Sheikh S, Alvi U, Soliven B, Rezania K. Drugs That Induce or Cause Deterioration of Myasthenia Gravis: An Update. J Clin Med. 2021 Apr 6;10(7):1537. doi: 10.3390/jcm10071537.

**PMID:** 33917535

**Citation:** Vymazal T, Krecmerova M, Bicek V, Lischke R. Feasibility of full and rapid neuromuscular blockade recovery with sugammadex in myasthenia gravis patients undergoing surgery - a series of 117 cases. Ther Clin Risk Manag. 2015 Oct 15;11:1593-6. doi: 10.2147/TCRM.S93009. eCollection 2015.

**PMID:** 26508869

**Citation:** van den Bersselaar LR, Gubbels M, Riazi S, Heytens L, Jungbluth H, Voermans NC, Snoeck MMJ. Mapping the current evidence on the anesthetic management of adult patients with neuromuscular disorders-a scoping review. Can J Anaesth. 2022 Jun;69(6):756-773. doi: 10.1007/s12630-022-02230-3. Epub 2022 Mar 23.

**PMID:** 35322378

**Citation:** Fernandes HDS, Ximenes JLS, Nunes DI, Ashmawi HA, Vieira JE. Failure of reversion of neuromuscular block with sugammadex in patient with myasthenia gravis: case report and brief review of literature. BMC Anesthesiol. 2019 Aug 17;19(1):160. doi: 10.1186/s12871-019-0829-0.

**PMID:** 31421671

**Citation:** No HJ, Yoo YC, Oh YJ, Lee HS, Jeon S, Kweon KH, Kim NY. Comparison between Sugammadex and Neostigmine after Video-Assisted Thoracoscopic Surgery-Thymectomy in Patients with Myasthenia Gravis: A Single-Center Retrospective Exploratory Analysis. J Pers Med. 2023 Sep 15;13(9):1380. doi: 10.3390/jpm13091380.

**PMID:** 37763148

**Citation:** Schaller SJ, Lewald H. Clinical pharmacology and efficacy of sugammadex in the reversal of neuromuscular blockade. Expert Opin Drug Metab Toxicol. 2016 Sep;12(9):1097-108. doi: 10.1080/17425255.2016.1215426. Epub 2016 Aug 3.

**PMID:** 27463265

**Citation:** Tsukada S, Shimizu S, Fushimi K. Rocuronium reversed with sugammadex for thymectomy in myasthenia gravis: A retrospective analysis of complications from Japan. Eur J Anaesthesiol. 2021 Aug 1;38(8):850-855. doi: 10.1097/EJA.0000000000001500.

**PMID:** 34226417

**Citation:** de Boer HD, Shields MO, Booij LH. Reversal of neuromuscular blockade with sugammadex in patients with myasthenia gravis: a case series of 21 patients and review of the literature. Eur J Anaesthesiol. 2014 Dec;31(12):715-21. doi: 10.1097/EJA.0000000000000153. No abstract available.

**PMID:** 25192270

**Citation:** Mouri H, Jo T, Matsui H, Fushimi K, Yasunaga H. Effect of Sugammadex on Postoperative Myasthenic Crisis in Myasthenia Gravis Patients: Propensity Score Analysis of a Japanese Nationwide Database. Anesth Analg. 2020 Feb;130(2):367-373. doi: 10.1213/ANE.0000000000004239.

**PMID:** 31124838

**Citation:** Fujimoto M, Terasaki S, Nishi M, Yamamoto T. Response to rocuronium and its determinants in patients with myasthenia gravis: A case-control study. Eur J Anaesthesiol. 2015 Oct;32(10):672-80. doi: 10.1097/EJA.0000000000000257.

**PMID:** 26086278

**Citation:** Lai HC, Huang TW, Tseng WC, Wu TS, Wu ZF. Sugammadex and postoperative myasthenic crisis. J Clin Anesth. 2019 Nov;57:63. doi: 10.1016/j.jclinane.2019.02.026. Epub 2019 Mar 12. No abstract available.

**PMID:** 30875518

**Citation:** Keating GM. Sugammadex: A Review of Neuromuscular Blockade Reversal. Drugs. 2016 Jul;76(10):1041-52. doi: 10.1007/s40265-016-0604-1.

**PMID:** 27324403

**Citation:** Petrun AM, Mekis D, Kamenik M. Successful use of rocuronium and sugammadex in a patient with myasthenia. Eur J Anaesthesiol. 2010 Oct;27(10):917-8. doi: 10.1097/EJA.0b013e3283392593. No abstract available.

**PMID:** 20375901

**Citation:** Kiss G, Lacour A, d'Hollander A. Fade of train-of-four ratio despite administration of more than 12 mg kg(-1) sugammadex in a myasthenia gravis patient receiving rocuronium. Br J Anaesth. 2013 May;110(5):854-5. doi: 10.1093/bja/aet098. No abstract available.

**PMID:** 23599531

**Citation:** Gurunathan U, Kunju SM, Stanton LML. Use of sugammadex in patients with neuromuscular disorders: a systematic review of case reports. BMC Anesthesiol. 2019 Nov 19;19(1):213. doi: 10.1186/s12871-019-0887-3.

**PMID:** 31744470

**Citation:** Jones RK, Caldwell JE, Brull SJ, Soto RG. Reversal of profound rocuronium-induced blockade with sugammadex: a randomized comparison with neostigmine. Anesthesiology. 2008 Nov;109(5):816-24. doi: 10.1097/ALN.0b013e31818a3fee.

**PMID:** 18946293

**Citation:** Blobner M, Eriksson LI, Scholz J, Motsch J, Della Rocca G, Prins ME. Reversal of rocuronium-induced neuromuscular blockade with sugammadex compared with neostigmine during sevoflurane anaesthesia: results of a randomised, controlled trial. Eur J Anaesthesiol. 2010 Oct;27(10):874-81. doi: 10.1097/EJA.0b013e32833d56b7.

**PMID:** 20683334

**Citation:** Suy K, Morias K, Cammu G, Hans P, van Duijnhoven WG, Heeringa M, Demeyer I. Effective reversal of moderate rocuronium- or vecuronium-induced neuromuscular block with sugammadex, a selective relaxant binding agent. Anesthesiology. 2007 Feb;106(2):283-8. doi: 10.1097/00000542-200702000-00016.

**PMID:** 17264722

**Citation:** Reid JE, Breslin DS, Mirakhur RK, Hayes AH. Neostigmine antagonism of rocuronium block during anesthesia with sevoflurane, isoflurane or propofol. Can J Anaesth. 2001 Apr;48(4):351-5. doi: 10.1007/BF03014962.

**PMID:** 11339776

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000020361

- Term: Paraneoplastic Syndromes, Nervous System

- ID: D000009423

- Term: Nervous System Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000010257

- Term: Paraneoplastic Syndromes

- ID: D000020274

- Term: Autoimmune Diseases of the Nervous System

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000019636

- Term: Neurodegenerative Diseases

- ID: D000020511

- Term: Neuromuscular Junction Diseases

- ID: D000009468

- Term: Neuromuscular Diseases

- ID: D000001327

- Term: Autoimmune Diseases

- ID: D000007154

- Term: Immune System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M12112

- Name: Myasthenia Gravis

- Relevance: HIGH

- As Found: Myasthenia Gravis

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M13170

- Name: Paraneoplastic Syndromes

- Relevance: LOW

- As Found: Unknown

- ID: M22160

- Name: Paraneoplastic Syndromes, Nervous System

- Relevance: LOW

- As Found: Unknown

- ID: M12367

- Name: Nervous System Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M4629

- Name: Autoimmune Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M22094

- Name: Autoimmune Diseases of the Nervous System

- Relevance: LOW

- As Found: Unknown

- ID: M21558

- Name: Neurodegenerative Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M22297

- Name: Neuromuscular Junction Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12411

- Name: Neuromuscular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T3973

- Name: Myasthenia Gravis

- Relevance: HIGH

- As Found: Myasthenia Gravis

### Condition Browse Module - Meshes

- ID: D000009157

- Term: Myasthenia Gravis

### Intervention Browse Module - Ancestors

- ID: D000002800

- Term: Cholinesterase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000018678

- Term: Cholinergic Agents

- ID: D000018377

- Term: Neurotransmitter Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000010277

- Term: Parasympathomimetics

- ID: D000001337

- Term: Autonomic Agents

- ID: D000018373

- Term: Peripheral Nervous System Agents

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: AnArAg

- Name: Anti-Arrhythmia Agents

- Abbrev: AdjAn

- Name: Adjuvants, Anesthesia

- Abbrev: Resp

- Name: Respiratory System Agents

### Intervention Browse Module - Browse Leaves

- ID: M12333

- Name: Neostigmine

- Relevance: HIGH

- As Found: Head and Neck Cancer

- ID: M1666

- Name: Rocuronium

- Relevance: LOW

- As Found: Unknown

- ID: M4590

- Name: Atropine

- Relevance: LOW

- As Found: Unknown

- ID: M6040

- Name: Cholinesterase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M20758

- Name: Cholinergic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M20504

- Name: Neurotransmitter Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000009388

- Term: Neostigmine

### Misc Info Module

- Version Holder: 2024-05-31
