Deep Neuromuscular Block and Sugammadex Versus Standard of Care on Quality of Recovery in Patient Undergo Elective Laparoscopic Cholecystectomy

• ClinicalTrials.gov Identifier: NCT02648503
• Recruitment Status: Unknown
• First Posted: January 7, 2016
• Last Update Posted: January 7, 2016
• Sponsor: Ho Chi Minh City University of Medicine and Pharmacy
• Collaborator: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Phan Ton Ngoc Vu, Ho Chi Minh City University of Medicine and Pharmacy

Study Description

Brief Summary:

Single center, prospective, randomized, single blinded, parallel group and controlled, assessor-blinded trial to compare the impact of Deep neuromuscular block and Sugammadex versus Standard of care on Quality of recovery in patient undergo elective laparoscopic cholecystectomy using PQRS at different time-point: 15 minutes (T15), 40 minutes (T40), one(D1) and three(D3) days after surgery

Condition or disease	Intervention/treatment	Phase
Neuromuscular Block	Drug: Deep neuromuscular block; Drug: Moderate neuromuscular block	Phase 4

Detailed Description:

• In the current study, the investigators investigate the effect of a deep NMB (TOF 0, PTC 1-2) with sugammadex against a moderate block (TOF 1-2) on quality of recovery in patient undergo elective laparoscopic cholecystectomy using PQRS at different time-point: 15 minutes (T15), 40 minutes (T40), one(D1) and three(D3) days after surgery.
• Based on a previous study comparing the Quality of recovery using PQRS between Neostigmine and Sugammadex, P. Amorim at al. showed that the percentage of patients fully awake at 40 min was 96.2% in the sugammadex group and 72.9% in the neostigmine group; the investigators expected the percentage of patient recovery at T40 will be 90% in group D (sugammadex) and 70% in group M (neostigmine)12. Recovery defined as return to the value of PQRS measured prior to surgery or higher. Using the formula for the sample size with α=0.05, Power: 80%, the sample size required per group is 60.
• Eligible patients will be randomly allocated into two groups using a computer-generated randomization before patients arrive to the operating room: Group D with deep, continuous neuromuscular blockade and Group M with moderate neuromuscular blockade.
• All information about group allocation, doses of rocuronium and sugammadex and neuromuscular data are recorded on a separate form and placed in a sealed opaque envelope when the patient is leaving the operating room. This will keep the personnel in the post-anesthesia care unit and the investigator collecting post-operative data blinded to group allocation.
• The investigators use acceleromyography (TOF-Watch SX) to monitor the level of neuromuscular blockage at the adductor pollicis muscle
• Involuntary movement will be recorded by anesthesia during surgery.
• Surgical condition will be rated by surgeons after surgery using five-point surgical condition scale (SRS)
• Hemodynamic changes using the noninvasive Nihon Konden (Nihon Konden, Japan), duration of surgery, drug dosages used during anesthesia, and duration from reversal to extubation, BIS, and ventilatory variables (tidal volume, respiratory rate, breathing pressure).

• Intra-abdominal pressure will be measured every 15 minutes from the peritoneal CO2 insufflation device. Pneumoperitoneum is obtained with insufflation of CO2 at 8 mmHg after the introduction of the trocars. In case of inadequate surgical conditions:

  • Increase of pre-set intra-abdominal pressure to 12-14 mmHg.
  • If still not adequate, patients will be given a bolus of rocuronium 0.075-0.15 mg/kg
  • If still not adequate, the surgeon will decide according to usual clinical practice.
• The intervention will be recorded by anesthesiologist and surgical condition rate will be measured at the time of surgery when they get worse.
• PQRS includes six domains of recovery: physiologic, nociceptive, emotive, activities of daily living, cognitive, and overall patient perspective. There is a series of questions in each domain2. PQRS data will be presented as percentage of patients that recovered for measurements taken at T15, T40, D1, and D3.
• Data of all patients that completed the baseline evaluation and T15 and T40 of the follow-up evaluations will be included in primary efficacy analysis.
• Continuous data will be presented as mean and standard deviation (SD) or median and range (minimum, maximum) and interquartile range (IQR, 25th 75th percentile). Categorical data will be presented as frequencies and percentages.
• The physiological domain data will be presented as mean and SD. The nociceptive domain data will be presented as mean with the 95% confidence intervals (CI).
• Categorical variables will be compared with the the Fisher exact test.
• For the comparison of continuous data, the Student's t test will be used. If there is substantial evidence of departures from normality, then the Mann-Whitney U-test will be performed as a sensitivity analysis.
• Data will be analyzed with the Statistical Package for the Social Sciences statistical software program. Statistical significance was set at P less than 0.05.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Study Start Date: March 2016
• Estimated Primary Completion Date: September 2016
• Estimated Study Completion Date: December 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Deep neuromuscular block; PTC=1-2	Drug: Deep neuromuscular block; Using rocuronium and reversal with sugammadex; Other Name: Esmeron and Bridion
Active Comparator: Moderate neuromuscular block; TOF=1-2	Drug: Moderate neuromuscular block; Using rocuronium and reversal with neostigmine (1 to 2 mg) and atropine (0.5 to 1 mg); Other Name: Esmeron and Neostigmin/Atropine

Outcome Measures

Primary Outcome Measures :

1. Quality of recovery [ Time Frame: 40 minutes (T40) after the end of surgery ]

   The primary outcome is to access the differences of Quality of recovery in the overall recovery of the Post-operative Quality Recovery Scale (PQRS) instrument at 40 minutes (T40) after the end of surgery between Deep NMB (reversed with Sugammadex) and Standard of care in patients who undergo Laparoscopic Cholecystectomy.

   PQRS includes six domains of recovery: physiologic, nociceptive, emotive, activities of daily living, cognitive, and overall patient perspective. There is a series of questions in each domain. The Postoperative Quality Recovery Scale (PQRS) will be performed and recorded face-to-face by anesthesiologists in hospital and by telephone after discharge. The PQRS is completed prior to surgery to provide baseline values. Recovery is defined as returning to baseline values or better in each of the questions or assessments.

Secondary Outcome Measures :

1. Quality of recovery [ Time Frame: 15 minutes (T15), and first day, 3 days after the end of surgery ]
   • The differences of Quality of recovery in the overall recovery of the PQRS instrument at 15 minutes (T15), and first day, 3 days after the end of surgery
   • The differences between each domain of PQRS instrument from 2 groups.
2. Shoulder tip pain [ Time Frame: first hour, 6 hours and 24 hours after surgery ]
   using a 100 mm visual analogue scale (VAS) (0 indicating no pain and 100 worst imaginable pain)

Other Outcome Measures:

1. Surgical condition [ Time Frame: intraoperation ]
   The satisfaction of surgeon with surgical condition from Deep Neuromuscular Block against Moderate Neuromuscular block. Surgeons will rate the surgical condition with a five-point surgical condition scale (SRS) ranging from 1= poor condition to 5= optimal surgical condition after the surgery
2. Time to discharge readiness [ Time Frame: Every 20 min from the start of admission to the post-anesthesia care unit (PACU), up to 2 hours ]
   Time to discharge readiness from the post-anesthesia care unit (PACU) using Post Anesthesia Discharge Score System (PADSS)
3. Duration of operation [ Time Frame: intraoperation ]
   Duration of surgery: from successful abdominal access with trocars to the skin closure Duration from reversal to extubation (TOF>0.9)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• All adult patients (> 18 years) scheduled for elective Laparoscopic Cholecystectomy with American Society of Anesthesiologist (ASA) class I-III in Hospital of University of Medicine and Pharmacy-Ho Chi Minh City

Exclusion Criteria:

• Patients with ASA class IV
• Age <18 years
• Inability to inform consent
• History or suspected with neuromuscular disorders
• Allergies to rocuronium or sugammadex, anesthetics or narcotics drugs
• A history of malignant hyperthermia
• A contraindication with neostigmine administration
• Pregnancy or breastfeeding
• Renal and liver insufficiency are excluded from this study

Contacts and Locations

Contacts

Contact: Vu TN Phan, PhD. MD; +84-908883458; vuphan682003@yahoo.com

Contact: Hung HM Phan, MD; +84-938183079; phanhaminhhung@gmail.com

Locations

Vietnam

Operation theathre

Ho Chi Minh, Vietnam, 700000

Contact: Vu TN Phan, PhD. MD +84-90883458 vuphan682003@yahoo.com

Sponsors and Collaborators

Ho Chi Minh City University of Medicine and Pharmacy

Merck Sharp & Dohme Corp.

Investigators

• Principal Investigator: Vu TN Phan, PhD. MD; University medical center HCMC

More Information

• Responsible Party: Phan Ton Ngoc Vu, PhD. MD, Ho Chi Minh City University of Medicine and Pharmacy
• ClinicalTrials.gov Identifier: NCT02648503
• Other Study ID Numbers: 8616-138
• First Posted: January 7, 2016
• Last Update Posted: January 7, 2016
• Last Verified: January 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Keywords provided by Phan Ton Ngoc Vu, Ho Chi Minh City University of Medicine and Pharmacy:

Sugammadex; Post-operative Quality Recovery Scale (PQRS)

Additional relevant MeSH terms:

Atropine; Rocuronium; Adjuvants, Anesthesia; Anti-Arrhythmia Agents; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Mydriatics; Parasympatholytics; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Neuromuscular Agents