Effect of Neuromuscular Blockade on Operating Conditions... | NCT02724111

Status Module

Name	Class
Merck Sharp & Dohme LLC	INDUSTRY

Oversight Module

Description Module

Detailed Description

Group treatment (Arms): group treated with restricted neuromuscular blockade (NMB) (Group RB); group treated with deep NMB (Group DB) → randomized allocation (subjects: motor-evoked potential [MEP] not monitored surgeries)
Inclusion criteria: American Society of Anesthesiologists (ASA) physical status I-II adults, aged 18-75 years, scheduled for elective spinal surgery (cervical or lumbar surgeries which have lesions no more than 3 spinal levels and not monitored by MEP) of duration >1 hour and prone position under total intravenous anesthesia (TIVA).
Exclusion criteria: Pregnancy, the receipt of medication known to interfere with neuromuscular blockade, diseases affecting neuromuscular transmission, and the history of hypersensitivity on rocuronium or sugammadex. The patients who will have hemodynamic instability, mean blood pressure increase or fall of > 30% from baseline (lasting for more than 5min), and blood loss > 1 L during surgery, and MEP monitored surgeries.
Outcome Measures
- Primary outcome: Mean value of peak inspiratory pressure recorded every 15 minutes.
- Secondary outcomes:
  1. The number of body movements (including cough or any diaphragm movement).
  2. The degree of bleeding of each patient scaled by surgeons (Intraoperative scale for assessment of operating condition of surgical field: 0 - No bleeding, 1 - Slight bleeding - no suctioning of blood required, 2 - Slight bleeding - occasional suctioning required but not threatened the operative field, 3 - Slight-bleeding - frequent suctioning of blood was required that threatens the operative field a few seconds after suctioning, 4 - Moderate bleeding - frequent suctioning of blood was required which threatens the operative field directly after suctioning, 5 - Sever bleeding - continuous suctioning of blood was required which severely threatened the operative field make the surgery not possible).
  3. The muscle tone of each patient scaled by surgeons (1: muscle tone is good, suitable for surgery; 2: muscle tone is moderate, but do not affect the operation; 3: muscle tone is hard, making the operation difficult.).
    - Three time-points of assessment of the muscle tone: ① At the placement of back muscle retractor for opening the operating site after the skin and subcutaneous incision, ② At the screw insertion through the pedicle of spine during surgery, ③ At the other period (overall muscle tone).
  4. Mean value of pressure of back muscle retractor placed in the operating site (recorded every 15 minutes): measured by the pressure probe placed between the retractor and the back muscle.
  5. Overall satisfaction of surgeons for the surgical condition will be assessed by the surgeons who perform surgery using numerical rating scale (NRS; 1-10) after surgery.
  6. Recovery profiles including eye opening time, extubation time and sedation score (the Observer's Assessment of Alertness/ Sedation (OAA/S) score; awake, 5 to unresponsive, 1) every 10 min for 1 hour at postanesthesia care unit (PACU).
  7. Postoperative adverse events

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
deep neuromuscular blockade	Experimental	This arm will be given sufficient dose of rocuronium. In this Arm group, rocuronium will be administered to maintain deep neuromuscular blockade [NMB] (train-of-four [TOF] count 0, post-tetanic count [PTC] of 1-2 twitches) until the end of surgery and the reversal of NMB will be performed by sugammadex 4 mg/kg at the end of surgery'.	Drug: sufficient dose of rocuronium
restricted neuromuscular blockade	Active Comparator	This arm will not be given sufficient dose of rocuronium. In this Arm group, sugammadex will be administered according to the prescribing indications (4 mg/kg for deep neuromuscular blockade [NMB] state or 2 mg/kg for moderate NMB or less) to reverse the NMB 10 min after position change (sugammadex 10 min after position change [a prone position]). Thereafter, muscle relaxants will not be injected any more throughout the surgery except the following situations: If the patients show any body movement during surgery or if surgeons express any complaint about muscle tone (the muscle tone: grade 3), rescue rocuronium 5 mg will be administered and the number of body movements and rescue rocuronium administration (dose) will be recorded.	Drug: sugammadex 10 min after position change

Name	Type	Description	Arm Group Labels	Other Names
sufficient dose of rocuronium	Drug		deep neuromuscular blockade	sugammadex at the end of surgery

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Mean Value of Peak Inspiratory Pressure	This outcome is the mean value of the peak inspiratory pressure measured at each 15 minute during the anesthesia, which can reflect the degree of the tone of respiratory muscles. As muscle tone increases, airway pressure usually increases due to increased tone of abdominal muscle and respiratory muscles including diaphragm. The longer the surgery goes, the higher the airway pressure gets. Also, as neurospinal surgeries are operated in the prone position, the potential for increased airway pressure is high. As airway pressure gets higher, intrathoracic pressure and intraabdominal pressure also become higher. These consequences may bring about similar results with detrimental effects derived from marked increase in intraabdominal pressure in laparoscopic abdominal surgeries	Every 15 minutes during anesthesia, up to 3 hours

Secondary Outcomes

Measure	Description	Time Frame
Mean Value of Pressure of Back Muscle Retractor	Mean value of pressure of back muscle retractor placed in the operating site (recorded every 15 minutes during the placement of the retractor): measured by the pressure probe placed between the retractor and the back muscle.	Every 15 minutes at the period of the retractor placement during surgery, up to 2 hours

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Byung Gun Lim, Ph.D.	Korea University Guro Hospital	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Korea University Guro Hospital		Seoul		08308	South Korea

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Deep Neuromuscular Blockade	This arm will be given sufficient dose of rocuronium. In this Arm group, rocuronium will be administered to maintain deep neuromuscular blockade [NMB] (train-of-four [TOF] count 0, post-tetanic count [PTC] of 1-2 twitches) until the end of surgery and the reversal of NMB will be performed by sugammadex 4 mg/kg at the end of surgery'. sufficient dose of rocuronium

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 4, 2016	Aug 8, 2017

Arm/Group Information

ID	Title	Description
BG000	Deep Neuromuscular Blockade	This arm will be given sufficient dose of rocuronium. In this Arm group, rocuronium will be administered to maintain deep neuromuscular blockade [NMB] (TOF count 0, post-tetanic count [PTC] of 1-2 twitches) until the end of surgery and the reversal of NMB will be performed by sugammadex 4 mg/kg at the end of surgery'. sufficient dose of rocuronium
BG001	Restricted Neuromuscular Blockade	This arm will be given restricted (not sufficient) dose of rocuronium. In this Arm group, sugammadex will be administered according to the prescribing indications (4 mg/kg for deep neuromuscular blockade [NMB] state or 2 mg/kg for moderate NMB or less) to reverse the NMB 10 min after position change (sugammadex 10 min after position change [a prone position]). Thereafter, muscle relaxants will not be injected any more throughout the surgery except the following situations: If the patients show any body movement during surgery or if surgeons express any complaint about muscle tone (the muscle tone: grade 3), rescue rocuronium 5 mg will be administered and the number of body movements and rescue rocuronium administration (dose) will be recorded. sugammadex 10 min after position change
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00043 BG00140 BG00283

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020
Between 18 and 65 years

Age, Continuous

Median

Full Range

years

Title

Denominators

Categories

Title	Measurements
	BG00061(37 to 75) BG00160(30 to 75) BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00031 BG00129 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Korean

Title	Measurements
	BG00043 BG00140 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

South Korea

Title	Measurements
	BG00043 BG00140 BG002

Height (m)

Mean

Standard Deviation

meter

Title

Denominators

Categories

Title	Measurements
	BG0001.59± 0.07 BG0011.58± 0.08 BG002

Weight (kg)

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00059.8± 8.5 BG00160± 6.9 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Mean Value of Peak Inspiratory Pressure

This outcome is the mean value of the peak inspiratory pressure measured at each 15 minute during the anesthesia, which can reflect the degree of the tone of respiratory muscles. As muscle tone increases, airway pressure usually increases due to increased tone of abdominal muscle and respiratory muscles including diaphragm. The longer the surgery goes, the higher the airway pressure gets. Also, as neurospinal surgeries are operated in the prone position, the potential for increased airway pressure is high. As airway pressure gets higher, intrathoracic pressure and intraabdominal pressure also become higher. These consequences may bring about similar results with detrimental effects derived from marked increase in intraabdominal pressure in laparoscopic abdominal surgeries

Posted

Mean

Standard Deviation

cmH2O

Every 15 minutes during anesthesia, up to 3 hours

ID	Title	Description
OG000	Deep Neuromuscular Blockade	This arm will be given sufficient dose of rocuronium. In this Arm group, rocuronium will be administered to maintain deep neuromuscular blockade [NMB] (TOF count 0, post-tetanic count [PTC] of 1-2 twitches) until the end of surgery and the reversal of NMB will be performed by sugammadex 4 mg/kg at the end of surgery'. sufficient dose of rocuronium
OG001	Restricted Neuromuscular Blockade	This arm will be given restricted (not sufficient) dose of rocuronium. In this Arm group, sugammadex will be administered according to the prescribing indications (4 mg/kg for deep neuromuscular blockade [NMB] state or 2 mg/kg for moderate NMB or less) to reverse the NMB 10 min after position change (sugammadex 10 min after position change [a prone position]). Thereafter, muscle relaxants will not be injected any more throughout the surgery except the following situations: If the patients show any body movement during surgery or if surgeons express any complaint about muscle tone (the muscle tone: grade 3), rescue rocuronium 5 mg will be administered and the number of body movements and rescue rocuronium administration (dose) will be recorded. sugammadex 10 min after position change

Units	Counts
Participants	OG00043 OG00140

Title

Denominators

Categories

Title	Measurements
	OG00018.4± 1.1 OG00120.2± 1.1

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		t-test, 2 sided		<0.001														Superiority

Secondary

Mean Value of Pressure of Back Muscle Retractor

Mean value of pressure of back muscle retractor placed in the operating site (recorded every 15 minutes during the placement of the retractor): measured by the pressure probe placed between the retractor and the back muscle.

Posted

Mean

Standard Deviation

mmHg

Every 15 minutes at the period of the retractor placement during surgery, up to 2 hours

ID	Title	Description
OG000	Deep Neuromuscular Blockade	This arm will be given sufficient dose of rocuronium. In this Arm group, rocuronium will be administered to maintain deep neuromuscular blockade [NMB] (TOF count 0, post-tetanic count [PTC] of 1-2 twitches) until the end of surgery and the reversal of NMB will be performed by sugammadex 4 mg/kg at the end of surgery'. sufficient dose of rocuronium
OG001	Restricted Neuromuscular Blockade	This arm will be given restricted (not sufficient) dose of rocuronium. In this Arm group, sugammadex will be administered according to the prescribing indications (4 mg/kg for deep neuromuscular blockade [NMB] state or 2 mg/kg for moderate NMB or less) to reverse the NMB 10 min after position change (sugammadex 10 min after position change [a prone position]). Thereafter, muscle relaxants will not be injected any more throughout the surgery except the following situations: If the patients show any body movement during surgery or if surgeons express any complaint about muscle tone (the muscle tone: grade 3), rescue rocuronium 5 mg will be administered and the number of body movements and rescue rocuronium administration (dose) will be recorded. sugammadex 10 min after position change

Secondary

Overall Satisfaction of Surgeons for the Surgical Condition

Overall satisfaction of surgeons for the surgical condition will be assessed by the surgeons who perform surgery using numerical rating scale (NRS; 1-10) after surgery (1, worst; 10, best).

Posted

Mean

Standard Deviation

Scores on a scale (NRS; 1-10)

After surgery

ID	Title	Description
OG000	Deep Neuromuscular Blockade	This arm will be given sufficient dose of rocuronium. In this Arm group, rocuronium will be administered to maintain deep neuromuscular blockade [NMB] (TOF count 0, post-tetanic count [PTC] of 1-2 twitches) until the end of surgery and the reversal of NMB will be performed by sugammadex 4 mg/kg at the end of surgery'. sufficient dose of rocuronium
OG001	Restricted Neuromuscular Blockade	This arm will be given restricted (not sufficient) dose of rocuronium. In this Arm group, sugammadex will be administered according to the prescribing indications (4 mg/kg for deep neuromuscular blockade [NMB] state or 2 mg/kg for moderate NMB or less) to reverse the NMB 10 min after position change (sugammadex 10 min after position change [a prone position]). Thereafter, muscle relaxants will not be injected any more throughout the surgery except the following situations: If the patients show any body movement during surgery or if surgeons express any complaint about muscle tone (the muscle tone: grade 3), rescue rocuronium 5 mg will be administered and the number of body movements and rescue rocuronium administration (dose) will be recorded. sugammadex 10 min after position change

Secondary

The Muscle Tone

The muscle tone of each patient at the screw insertion through the pedicle of spine during surgery scaled by surgeons (1: muscle tone is good, suitable for surgery; 2: muscle tone is moderate, but do not affect the operation; 3: muscle tone is hard, making the operation difficult.).

Posted

Mean

Standard Deviation

Scores on a scale (NRS; 1-3)

at the screw insertion through the pedicle of spine during surgery

ID	Title	Description
OG000	Deep Neuromuscular Blockade	This arm will be given sufficient dose of rocuronium. In this Arm group, rocuronium will be administered to maintain deep neuromuscular blockade [NMB] (TOF count 0, post-tetanic count [PTC] of 1-2 twitches) until the end of surgery and the reversal of NMB will be performed by sugammadex 4 mg/kg at the end of surgery'. sufficient dose of rocuronium
OG001	Restricted Neuromuscular Blockade	This arm will be given restricted (not sufficient) dose of rocuronium. In this Arm group, sugammadex will be administered according to the prescribing indications (4 mg/kg for deep neuromuscular blockade [NMB] state or 2 mg/kg for moderate NMB or less) to reverse the NMB 10 min after position change (sugammadex 10 min after position change [a prone position]). Thereafter, muscle relaxants will not be injected any more throughout the surgery except the following situations: If the patients show any body movement during surgery or if surgeons express any complaint about muscle tone (the muscle tone: grade 3), rescue rocuronium 5 mg will be administered and the number of body movements and rescue rocuronium administration (dose) will be recorded. sugammadex 10 min after position change

Secondary

The Number of Body Movements

The number of body movements (including cough or any diaphragm movement) observed during the surgery.

Posted

Mean

Standard Deviation

number of event

At the occurrence of the event during surgery, up to 3 hours

ID	Title	Description
OG000	Deep Neuromuscular Blockade	This arm will be given sufficient dose of rocuronium. In this Arm group, rocuronium will be administered to maintain deep neuromuscular blockade [NMB] (TOF count 0, post-tetanic count [PTC] of 1-2 twitches) until the end of surgery and the reversal of NMB will be performed by sugammadex 4 mg/kg at the end of surgery'. sufficient dose of rocuronium
OG001	Restricted Neuromuscular Blockade	This arm will be given restricted (not sufficient) dose of rocuronium. In this Arm group, sugammadex will be administered according to the prescribing indications (4 mg/kg for deep neuromuscular blockade [NMB] state or 2 mg/kg for moderate NMB or less) to reverse the NMB 10 min after position change (sugammadex 10 min after position change [a prone position]). Thereafter, muscle relaxants will not be injected any more throughout the surgery except the following situations: If the patients show any body movement during surgery or if surgeons express any complaint about muscle tone (the muscle tone: grade 3), rescue rocuronium 5 mg will be administered and the number of body movements and rescue rocuronium administration (dose) will be recorded. sugammadex 10 min after position change

Secondary

The Degree of Bleeding

2.The degree of bleeding of each patient scaled by surgeons (Intraoperative scale for assessment of operating condition of surgical field: 0 - No bleeding, 1 - Slight bleeding - no suctioning of blood required, 2 - Slight bleeding - occasional suctioning required but not threatened the operative field, 3 - Slight-bleeding - frequent suctioning of blood was required that threatens the operative field a few seconds after suctioning, 4 - Moderate bleeding - frequent suctioning of blood was required which threatens the operative field directly after suctioning, 5 - Severe bleeding - continuous suctioning of blood was required which severely threatened the operative field make the surgery not possible).

Posted

Mean

Standard Deviation

Scores on a scale (NRS; 0-5)

Continuously observed during the whole period of surgery, up to 3 hours

ID	Title	Description
OG000	Deep Neuromuscular Blockade	This arm will be given sufficient dose of rocuronium. In this Arm group, rocuronium will be administered to maintain deep neuromuscular blockade [NMB] (TOF count 0, post-tetanic count [PTC] of 1-2 twitches) until the end of surgery and the reversal of NMB will be performed by sugammadex 4 mg/kg at the end of surgery'. sufficient dose of rocuronium
OG001	Restricted Neuromuscular Blockade	This arm will be given restricted (not sufficient) dose of rocuronium. In this Arm group, sugammadex will be administered according to the prescribing indications (4 mg/kg for deep neuromuscular blockade [NMB] state or 2 mg/kg for moderate NMB or less) to reverse the NMB 10 min after position change (sugammadex 10 min after position change [a prone position]). Thereafter, muscle relaxants will not be injected any more throughout the surgery except the following situations: If the patients show any body movement during surgery or if surgeons express any complaint about muscle tone (the muscle tone: grade 3), rescue rocuronium 5 mg will be administered and the number of body movements and rescue rocuronium administration (dose) will be recorded. sugammadex 10 min after position change

Secondary

Recovery Time (Time to Reach Sedation Score 5 at Postanesthesia Care Unit (PACU).

the time to reach sedation score 5 (the Observer's Assessment of Alertness/ Sedation (OAA/S) score; awake, 5 to unresponsive, 1) at PACU

Posted

Mean

Standard Deviation

minute

every 10 min for 1 hour at PACU.

ID	Title	Description
OG000	Deep Neuromuscular Blockade	This arm will be given sufficient dose of rocuronium. In this Arm group, rocuronium will be administered to maintain deep neuromuscular blockade [NMB] (TOF count 0, post-tetanic count [PTC] of 1-2 twitches) until the end of surgery and the reversal of NMB will be performed by sugammadex 4 mg/kg at the end of surgery'. sufficient dose of rocuronium
OG001	Restricted Neuromuscular Blockade	This arm will be given restricted (not sufficient) dose of rocuronium. In this Arm group, sugammadex will be administered according to the prescribing indications (4 mg/kg for deep neuromuscular blockade [NMB] state or 2 mg/kg for moderate NMB or less) to reverse the NMB 10 min after position change (sugammadex 10 min after position change [a prone position]). Thereafter, muscle relaxants will not be injected any more throughout the surgery except the following situations: If the patients show any body movement during surgery or if surgeons express any complaint about muscle tone (the muscle tone: grade 3), rescue rocuronium 5 mg will be administered and the number of body movements and rescue rocuronium administration (dose) will be recorded. sugammadex 10 min after position change

Secondary

Adverse Events : The Postoperative Nausea and Vomiting Occurrence in Subject

The occurrence of any adverse events was recorded in the post-anesthesia care unit (PACU) and a ward during the postoperative 24 hours.

Posted

Count of Participants

Participants

during the postoperative 24 hours

ID	Title	Description
OG000	Deep Neuromuscular Blockade	This arm will be given sufficient dose of rocuronium. In this Arm group, rocuronium will be administered to maintain deep neuromuscular blockade [NMB] (TOF count 0, post-tetanic count [PTC] of 1-2 twitches) until the end of surgery and the reversal of NMB will be performed by sugammadex 4 mg/kg at the end of surgery'. sufficient dose of rocuronium
OG001	Restricted Neuromuscular Blockade	This arm will be given restricted (not sufficient) dose of rocuronium. In this Arm group, sugammadex will be administered according to the prescribing indications (4 mg/kg for deep neuromuscular blockade [NMB] state or 2 mg/kg for moderate NMB or less) to reverse the NMB 10 min after position change (sugammadex 10 min after position change [a prone position]). Thereafter, muscle relaxants will not be injected any more throughout the surgery except the following situations: If the patients show any body movement during surgery or if surgeons express any complaint about muscle tone (the muscle tone: grade 3), rescue rocuronium 5 mg will be administered and the number of body movements and rescue rocuronium administration (dose) will be recorded. sugammadex 10 min after position change

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Deep Neuromuscular Blockade	This arm will be given sufficient dose of rocuronium. In this Arm group, rocuronium will be administered to maintain deep neuromuscular blockade [NMB] (TOF count 0, post-tetanic count [PTC] of 1-2 twitches) until the end of surgery and the reversal of NMB will be performed by sugammadex 4 mg/kg at the end of surgery'. sufficient dose of rocuronium	0	43	0	43	11	43
EG001	Restricted Neuromuscular Blockade	This arm will be given restricted (not sufficient) dose of rocuronium. In this Arm group, sugammadex will be administered according to the prescribing indications (4 mg/kg for deep neuromuscular blockade [NMB] state or 2 mg/kg for moderate NMB or less) to reverse the NMB 10 min after position change (sugammadex 10 min after position change [a prone position]). Thereafter, muscle relaxants will not be injected any more throughout the surgery except the following situations: If the patients show any body movement during surgery or if surgeons express any complaint about muscle tone (the muscle tone: grade 3), rescue rocuronium 5 mg will be administered and the number of body movements and rescue rocuronium administration (dose) will be recorded. sugammadex 10 min after position change	0	40	0	40	8	40

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
nausea or vomiting	Gastrointestinal disorders		Non-systematic Assessment	This adverse event is the postoperative nausea and vomiting occurred during the postoperative 24 hours. The symptoms were all resolved well after administration of antiemetics.	EG00011 affected43 at risk EG0018 affected40 at risk

ID	Term
D001847	Bone Diseases
D009140	Musculoskeletal Diseases

ID	Term
D047408	gamma-Cyclodextrins
D003505	Cyclodextrins
D047028	Macrocyclic Compounds
D011083	Polycyclic Compounds
D003912	Dextrins
D013213	Starch
D005936	Glucans
D011134	Polysaccharides
D002241	Carbohydrates