A Study Comparing the Use of Deep or Standard Neuromuscular Blockade in Combination With Low or Standard Insufflation Pressures in Participants Undergoing Laparoscopic Cholecystectomy (P07982)

NCT01728584 | Completed Phase 4 Results

• 3 other identifiers: P07982MK-8616-0762012-001886-33
• Study Type: interventional
• Target: 127
• Locations: 2 countries
• Sites: 2

Brief Summary

The purpose of this pilot study is to compare the use of deep or standard neuromuscular blockade (NMB) in combination with low or standard insufflation pressure in participants undergoing a surgical procedure, laparoscopic cholecystectomy. Insufflation refers to the injection of carbon dioxide into the abdomen during the laparoscopic surgery, to allow visualization of and access to the surgical field. The primary hypothesis of the study is that the use of sustained deep NMB improves the surgeon's overall satisfaction with surgical conditions as compared to standard NMB. The in-patient surgery is performed on Day 1 and the participant remains hospitalized for at least 48 hours following the surgery (or at least 24 hours following the surgery, if local practice does not allow 48 hours of hospitalization post surgery). On Day 8, a follow-up visit/contact including all participants occurs.

Conditions

Gallbladder Disease

Outcome Measures

Primary Outcomes (2)

• Score on Surgeon's Assessment of Overall Satisfaction With the Surgical Conditions: By Depth of NMB (Standard, Deep) and Insufflation Pressure (Standard, Low)

  At the end of the procedure the surgeon responds to the following question, using an 11-point scale from 0 (poor, needed intervention) to 10 (excellent): "How satisfied were you overall with the surgical conditions related to anesthesia and pneumoperitoneum during the surgery you just performed?" If at any time the surgeon requests a rescue intervention, the overall assessment of surgical conditions should be rated as 0 (=poor, needed intervention). The surgeon will rate the surgical conditions according to his opinion but if a rescue intervention has been applied, that individual participant will be counted with a score of zero in the analysis.

  End of surgery (Day 1)

• Score on Surgeon's Assessment of Overall Satisfaction With the Surgical Conditions: By Treatment Arm

  At the end of the procedure the surgeon responds to the following question, using an 11-point scale from 0 (poor, needed intervention) to 10 (excellent): "How satisfied were you overall with the surgical conditions related to anesthesia and pneumoperitoneum during the surgery you just performed?" If at any time the surgeon requests a rescue intervention, the overall assessment of surgical conditions should be rated as 0 (=poor, needed intervention). The surgeon will rate the surgical conditions according to his opinion but if a rescue intervention has been applied, that individual participant will be counted with a score of zero in the analysis.

  End of surgery (Day 1)

Secondary Outcomes (12)

• Participant's Overall Average Pain Score in the First 24 Hours After Administration of Sugammadex: By Depth of NMB (Standard, Deep) and Insufflation Pressure (Standard, Low)

  Up to 24 hours after administration of sugammadex on Day 1

• Participant's Overall Average Pain Score in the First 24 Hours After Administration of Sugammadex: By Treatment Arm

  Up to 24 hours after administration of sugammadex on Day 1

• Score on Surgeon's Assessment of Overall Satisfaction With the Visibility of the Surgical Field: By Depth of NMB (Standard, Deep)

  End of surgery (Day 1)

• Score on Surgeon's Assessment of the Overall Adequacy of Muscle Relaxation During Surgery: By Depth of NMB (Standard, Deep)

  End of surgery (Day 1)

• Score on Surgeon's Assessment of the Overall Adequacy of Insufflation Pressure During Surgery: By Depth of NMB (Standard, Deep)

  End of surgery (Day 1)

Study Arms (4)

Standard NMB and Standard Insufflation Pressure

EXPERIMENTAL

Treatment condition for this arm is Standard NMB (depth of blockade at a targeted Train of Four \[TOF\] ratio of 10%)/Standard insufflation pressure (starting pressure of 12 mmHg).

Drug: Rocuronium; Other: Insufflation; Drug: Sugammadex

Standard NMB and Low Insufflation Pressure

EXPERIMENTAL

Treatment condition for this arm is Standard NMB (depth of blockade at a targeted TOF ratio of 10%)/Low insufflation pressure (starting pressure of 8 mmHg).

Drug: Rocuronium; Other: Insufflation; Drug: Sugammadex

Deep NMB and Standard Insufflation Pressure

EXPERIMENTAL

Treatment condition for this arm is Deep NMB (depth of blockade of 1-2 PTCs)/Standard insufflation pressure (starting pressure of 12 mmHg).

Drug: Rocuronium; Other: Insufflation; Drug: Sugammadex

Deep NMB and Low Insufflation Pressure

EXPERIMENTAL

Treatment condition for this arm is Deep NMB (depth of blockade of 1-2 PTCs)/Low insufflation pressure (starting pressure of 8 mmHg).

Drug: Rocuronium; Other: Insufflation; Drug: Sugammadex

Interventions

Rocuronium DRUG

NMB will be induced by intravenous (IV) administration of a bolus dose of 0.45 mg/kg rocuronium. NMB will be maintained using rocuronium infusion or additional bolus doses as needed for the management of NMB to the targeted depth according to the assigned treatment condition. - Standard NMB - administration of neuromuscular blocking agent (NMBA) titrated to a depth of blockade at a targeted TOF ratio of 10% (range: TOF count 2-3 to TOF ratio of 20%). - Deep NMB - administration of NMBA titrated to a targeted depth of 1-2 Post Tetanic Counts (PTCs) (range: 1-5 PTC).

Also known as: Zemuron® Injection (rocuronium bromide)

Deep NMB and Low Insufflation Pressure; Deep NMB and Standard Insufflation Pressure; Standard NMB and Low Insufflation Pressure; Standard NMB and Standard Insufflation Pressure

Insufflation OTHER

Insufflation (injection) of carbon dioxide will be used to induce pneumoperitoneum, which is presence of air or gas in the abdominal (peritoneal) cavity. * Standard insufflation pressure - a starting pressure of 12 mmHg will be used. * Low insufflation pressure - a starting pressure of 8 mmHg will be used.

Deep NMB and Low Insufflation Pressure; Deep NMB and Standard Insufflation Pressure; Standard NMB and Low Insufflation Pressure; Standard NMB and Standard Insufflation Pressure

Sugammadex DRUG

NMB will be reversed with IV administration of 2 or 4 mg/kg sugammadex (depending on the depth of NMB) according to the approved label for sugammadex.

Also known as: sugammadex sodium injection, SCH 900616, Org 25969, Bridion®

Deep NMB and Low Insufflation Pressure; Deep NMB and Standard Insufflation Pressure; Standard NMB and Low Insufflation Pressure; Standard NMB and Standard Insufflation Pressure

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• American Society of Anesthesiologists (ASA) Class 1 or 2 or 3
• Scheduled to undergo an elective in-patient laparoscopic cholecystectomy procedure under general anesthesia with total intravenous anesthesia (TIVA) using propofol and remifentanil
• Eligible to undergo rocuronium-induced NMB for endotracheal intubation and maintenance of NMB
• Will recover in the post-anesthesia care unit (PACU) and remain in the hospital for at least 48 hours following the surgical procedure (or at least 24 hours following the surgical procedure, if local practice does not allow 48 hours of hospitalization post surgery)
• Body mass index (BMI) ≤35
• Willing and able to adhere to visit schedules including all required study assessments on Day 3 through 8 (daily pain and medication diary entry)
• For sexually active female participants of child-bearing potential - able to use a medically accepted method of contraception through 7 days after receiving protocol-specified medication

You may not qualify if:

• Neuromuscular disorders that may affect NMB and/or trial assessments
• Lifetime history of previous abdominal surgery, including laparotomies, Cesarean section, laparoscopic procedures or diagnostic laparoscopies
• Substance abuse or dependence (excluding nicotine) within the past 6 months
• History of a chronic pain condition (requiring continuous/daily pain medication prior to surgery)
• For female participants - lifetime history of a Cesarean section, or has given birth to one or more children within the last year, or is currently pregnant or has the intention to become pregnant between randomization and pregnancy follow-up contact ≥30 days after administration of trial treatments (rocuronium, sugammadex)
• Evidence of acute cholecystitis
• Dialysis-dependency or suspected of having severe renal insufficiency
• Significant hepatic dysfunction that would prevent participation in the trial
• History of or family history of malignant hyperthermia
• Allergy to trial treatments (rocuronium or sugammadex) or their excipients, to opioids/opiates, or other medication used during general anesthesia
• Received or is planned to receive toremifene or fusidic acid within 24 hours before or after receiving rocuronium or sugammadex
• Expected transfer to an Intensive Care Unit after surgery
• Any clinically significant condition or situation, other than the reason for the cholecystectomy that would interfere with the trial evaluations or optimal participation in the trial
• Used any investigational drugs within 30 days of randomization
• Participated in any other clinical trial within 30 days of signing the informed consent form of the current trial

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (2)

Merck Sharp & Dohme GmbH

Haar, Germany

Location

MSD Italia S.r.l.

Rome, Italy

Location

Related Publications (1)

• Rosenberg J, Herring WJ, Blobner M, Mulier JP, Rahe-Meyer N, Woo T, Li MK, Grobara P, Assaid CA, Fennema H, Szegedi A. Deep Neuromuscular Blockade Improves Laparoscopic Surgical Conditions: A Randomized, Controlled Study. Adv Ther. 2017 Apr;34(4):925-936. doi: 10.1007/s12325-017-0495-x. Epub 2017 Mar 1.

  PMID: 28251555 RESULT

MeSH Terms

Conditions

Gallbladder Diseases

Interventions

Rocuronium; Insufflation; Sugammadex

Condition Hierarchy (Ancestors)

Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Androstanols; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Diagnostic Techniques and Procedures; Diagnosis; Therapeutics; gamma-Cyclodextrins; Cyclodextrins; Macrocyclic Compounds; Dextrins; Starch; Glucans; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2012
• First Posted: November 20, 2012
• Study Start: November 28, 2012
• Primary Completion: April 29, 2014
• Study Completion: April 29, 2014
• Last Updated: October 17, 2018
• Results First Posted: March 23, 2015

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will share

Locations

DE (1); IT (1)