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)

NCT ID: NCT01728584

Last Updated: 2018-10-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 127 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-28
• Study Completion Date: 2014-04-29

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.

Detailed Description

During procedure, surgeon (who was blinded to random assignment) could request that unblinded anesthetist change the randomized treatment conditions (called a "rescue intervention"), if surgeon considered surgical conditions to be unacceptable. This was to be done systematically as follows: If the participant is on standard NMB, the preferred rescue intervention should be to increase the NMB to a depth of 1-2 PTCs; for such a participant the second option (if participant is also on low insufflation pressure) should be the increase of insufflation pressure by 4 mmHg. If the participant is already on deep NMB, the preferred option should be (if participant is also on low insufflation pressure) the increase of insufflation pressure by 4 mmHg.

Conditions

Gallbladder Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Standard NMB and Standard Insufflation Pressure

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).

Group Type: EXPERIMENTAL

Rocuronium

Intervention Type: 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).

Insufflation

Intervention Type: 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.

Sugammadex

Intervention Type: 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.

Standard NMB and Low Insufflation Pressure

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).

Group Type: EXPERIMENTAL

Rocuronium

Intervention Type: 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).

Insufflation

Intervention Type: 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.

Sugammadex

Intervention Type: 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.

Deep NMB and Standard Insufflation Pressure

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

Group Type: EXPERIMENTAL

Rocuronium

Intervention Type: 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).

Insufflation

Intervention Type: 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.

Sugammadex

Intervention Type: 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.

Deep NMB and Low Insufflation Pressure

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

Group Type: EXPERIMENTAL

Rocuronium

Intervention Type: 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).

Insufflation

Intervention Type: 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.

Sugammadex

Intervention Type: 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.

Interventions

Rocuronium

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).

Intervention Type: DRUG

Insufflation

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.

Intervention Type: OTHER

Sugammadex

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.

Intervention Type: DRUG

Other Intervention Names

Zemuron® Injection (rocuronium bromide); sugammadex sodium injection; SCH 900616; Org 25969; Bridion®

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• Participated in any other clinical trial involving any personnel of the investigational or Sponsor staff directly involved with this trial
• Is a family member of any personnel of the investigational or Sponsor staff directly involved with this trial

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Merck Sharp & Dohme GmbH

Haar, , Germany

MSD Italia S.r.l.

Rome, , Italy

Countries

Germany; Italy

References

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.

Reference Type: RESULT

PMID: 28251555 (View on PubMed)

Other Identifiers

MK-8616-076

Identifier Type: OTHER

Identifier Source: secondary_id

2012-001886-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

P07982

Identifier Type: -

Identifier Source: org_study_id