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)

Condition(s) targeted: Gallbladder Disease

Intervention: Rocuronium (Drug); Insufflation (Other); Sugammadex (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Merck Sharp & Dohme Corp.

Official(s) and/or principal investigator(s):
Medical Director, Study Director, Affiliation: Merck Sharp & Dohme Corp.

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.

Official title: Randomized, Controlled, Parallel-Group, Double-Blind Trial to Compare the Use of Deep or Standard Neuromuscular Blockade in Combination With Low or Standard Insufflation Pressures Using a 2x2 Factorial Design in Patients Undergoing Laparoscopic Cholecystectomy (Protocol No. MK-8616-076-03 Also Known as SCH 900616, P07982)

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

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

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

Secondary outcome:

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)

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

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

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

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

Number of Times Participant's Movements or Increased Muscle Tone Interfered With the Surgical Conditions During Laparoscopy: By Depth of NMB (Standard, Deep)

Score on Surgeon's Assessment of the Effect Participant's Movements During Surgery Had on the Overall Surgical Procedure: By Depth of NMB (Standard, Deep)

Number of Participants With Rescue Actions Performed During Surgery in Order to Improve Insufficient Surgical Conditions: By Treatment Arm

Participant's Daily Assessment of Overall Pain at Rest During Post Operative Period: By Treatment Arm

Participant's Daily Assessment of Provoked Pain During Post Operative Period: By Treatment Arm

Participant's Daily Assessment of Shoulder Pain During Post Operative Period: By Treatment Arm

Number of Participants Using Pain/Analgesic Medication During Post Operative Period: By Treatment Arm

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Merck Sharp & Dohme GmbH, Haar, Germany

MSD Italia S.r.l., Rome, Italy

Starting date: November 2012
Last updated: May 11, 2015