Clinical trial NCT00724932: Comparison of Sugammadex With Neostigmine During Laparoscopic Cholecystectomy or Appendectomy (P05699)
Official title: A Multi-center, Randomized, Parallel-group, Comparative, Active-controlled, Safety-assessor Blinded Trial in Adult Subjects Comparing the Efficacy and Safety of Sugammadex (SCH 900616, ORG 25969) Administered at 1-2 PTC With Neostigmine Administered at Reappearance of T2 in Subjects Undergoing Laparoscopic Cholecystectomy or Appendectomy Under Propofol Anesthesia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anesthesia, General
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2008-07-30
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The current trial was designed to demonstrate faster recovery from a neuromuscular blockade (NMB) induced by rocuronium after reversal at 1-2 Post Tetanic Count (PTC) by 4.0 mg.kg-1 sugammadex compared to 50 µg.kg-1 neostigmine at reappearance of second twitch (T2) in participants undergoing laparoscopic cholecystectomy or appendectomy under propofol anesthesia, to compare safety and to evaluate operating room and Post Anesthetic Care Unit (PACU) length of stay.

Detailed description: In those surgical procedures where a neuromuscular block is desired for intubation and/or avoid unwanted muscular activity, anesthesiologists may use a more profound NMB until the end of surgery, e.g. in open abdominal procedures or during laparoscopic procedures in order to improve surgical conditions. Reversal with sugammadex at a dose of 4.0 mg.kg-1 at 1-2 PTC after an intubation dose of 0.6 mg.kg-1 or maintenance dosing rocuronium has been found to be both safe and efficacious in previous clinical trials but has never been investigated exclusively in participants undergoing laparoscopic cholecystectomy or appendectomy.

With sugammadex profound muscle relaxation may now be provided right up to the end of the surgical procedure. This may lead to improved Patient Outcomes, such as improvement in the time from end of surgery to the discharge to the PACU. In this multi-center, randomized, parallel-group, active-controlled, safety-assessor blinded trial such benefits will be further investigated.

Eligibility criteria: Inclusion Criteria:

* Participants of American Society of Anesthesiologists class 1-3
* Participants of age above or equal to the age of 18 years
* Participants who are scheduled to undergo a laparoscopic cholecystectomy or appendectomy under general anesthesia requiring neuromuscular relaxation with rocuronium, and if applicable, maintenance of neuromuscular blockade
* Participants who have given written informed consent

Exclusion Criteria:

* Participants in whom a difficult intubation because of anatomical malformations is expected
* Participants known or suspected to have neuromuscular disorders affecting NMB
* Participants known or suspected to have a significant renal dysfunction
* Participants known or suspected to have a severe hepatic dysfunction
* Participants known or suspected to have (family) history of malignant hyperthermia
* Participants known or suspected to have an allergy to opioids, muscle relaxants or other medication used during general anesthesia
* Participants in whom the use of neostigmine and/or atropine is contraindicated
* Female participants who are pregnant (pregnancy will be excluded for women both from medical history and by a human chorionic gonadotropin (hCG) test within 24h before surgery, except for women who are not of childbearing potential, i.e. at least 2 years menopausal or have undergone tubal ligation or a hysterectomy)
* Female participants who are breast-feeding
* Participants who participated in another clinical trial not pre-approved by the sponsor, within 30 days of entering into trial 19.4.318 (P05699)
* Participants who have already participated in a sugammadex trial

Primary outcomes:
measure: Time From Start of Administration of Investigational Medicinal Product (IMP, Sugammadex or Neostigmine) to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9
timeFrame: From start of IMP administration to recovery of T4/T1 ratio to 0.9 (ranging from ~2 minutes to ~9 minutes)
Secondary outcomes:
measure: Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.7
timeFrame: From start of IMP administration to recovery of T4/T1 Ratio to 0.7 (ranging from ~2 minutes to ~5 minutes)
measure: Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.8
timeFrame: From start of IMP administration to recovery of T4/T1 Ratio to 0.8 (ranging from ~2 minutes to ~6 minutes)
measure: Number of Participants Who Experienced Pre-treatment Serious Adverse Events (SAEs) and Post-treatment SAEs
timeFrame: From signing of informed consent to end of trial (7 days after surgery)
measure: Number of Participants Who Experienced Pre-treatment Non-serious Adverse Events (AEs) and Post-treatment Non-serious AEs
timeFrame: From signing of informed consent to end of trial (7 days after surgery)
Other outcomes:
measure: Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.5 and 0.6
timeFrame: From start of IMP administration to recovery of T4/T1 Ratio to 0.5 and 0.6 (ranging from ~1 minute to ~4 minutes)
measure: Time From Start of Administration of the Last Dose of Rocuronium to Recovery of the T4/T1 Ratio to 0.5, 0.6, 0.7, 0.8 and 0.9
timeFrame: From start of last dose of rocuronium to recovery of T4/T1 Ratio to 0.5, 0.6, 0.7, 0.8 and 0.9 (ranging from ~12 minutes to ~36 minutes)
measure: Time From Start of Administration of the Last Dose of Rocuronium to the Time of 1-2 PTC in the 4.0 mg.Kg-1 Sugammadex Group
timeFrame: From last dose of rocuronium to 1-2 PTC (up to ~9 minutes)
measure: Time From Start of Administration of the Last Dose of Rocuronium to the Time of Reappearance of T2 in the 50 μg.Kg-1 Neostigmine Group
timeFrame: From last dose of rocuronium to reappearance of T2 (up to ~26 minutes)
measure: Mean Systolic Blood Pressure
timeFrame: At screening, pre-rocuronium, pre-IMP, at 2, 5, 10, and 30 minutes post-IMP, and at the post-anesthetic visit (the day after surgery)
measure: Mean Diastolic Blood Pressure
timeFrame: At screening, pre-rocuronium, pre-IMP, at 2, 5, 10, and 30 minutes post-IMP, and at the post-anesthetic visit (the day after surgery)
measure: Mean Heart Rate
timeFrame: At screening, pre-rocuronium, pre-IMP, at 2, 5, 10, and 30 minutes post-IMP, and at the post-anesthetic visit (the day after surgery)
measure: Number of Participants Who Had Physical Examinations
timeFrame: At screening (within 7 days prior to surgery) and at the post-anesthetic visit (the day after surgery)
measure: Number of Participants With Train-of-Four- (TOF-) Watch® SX and Arm Board Related Adverse Events
timeFrame: From induction of anesthesia to recovery from NMB (up to ~3 hours)
measure: Number of Participants With Reoccurrence of Neuromuscular Blockade Based on the Train-of-Four- (TOF-) Watch® SX Recording (i.e. a Decline in T4/T1 Ratio From >=0.9 to <0.8 in at Least Three Consecutive TOF Values)
timeFrame: Up to 30 minutes after IMP administration
measure: Number of Participants With Clinical Evidence of Reoccurrence of Neuromuscular Blockade or Residual Neuromuscular Blockade (Routine Oxygen Saturation by Pulse Oximetry and Breath Frequency Measurement)
timeFrame: Up to 24 hours after IMP administration
measure: Number of Participants With Events Due to a Possible Interaction of Sugammadex With Endogenous Compounds or With Exogenous Compounds Other Than Rocuronium
timeFrame: Up to 7 days after IMP administration
measure: Monitoring of Clinical Signs of Recovery According to Routine Anesthetic Procedures at the Trial Sites
timeFrame: Up to PACU discharge (up to ~4.5 hours)
measure: Number of Female Participants or Partners of Male Participants Who Became Pregnant During Study
timeFrame: Up to 30 days after IMP administration
measure: Time From Operating Room Admission to Operating Room Discharge Ready
timeFrame: From Operating Room admission to Operating Room discharge ready (up to ~3 hours)
measure: Time From Operating Room Admission to Actual Operating Room Discharge
timeFrame: From Operating Room admission to actual Operating Room discharge (up to ~3 hours)
measure: Time From Operating Room Discharge Ready to Actual Operating Room Discharge
timeFrame: From Operating Room discharge ready to actual Operating Room discharge (up to ~5 minutes)
measure: Time From Start of IMP Administration to T4/T1 Ratio of <=0.60, >0.60 - <=0.70, >0.70 - <=0.80, >0.80 - <0.90 and >=0.90
timeFrame: From start of IMP administration to recovery of the T4/T1 ratio to the designated value (ranging from ~1 minute to ~10 minutes)
measure: Time From Start of IMP Administration to Tracheal Extubation
timeFrame: From start of IMP administration to tracheal extubation (up to ~21 minutes)
measure: Time From Start of IMP Administration to Operating Room Discharge Ready
timeFrame: From start of IMP administration to Operating Room discharge ready (up to ~21 minutes)
measure: Time From Start of IMP Administration to Actual Operating Room Discharge
timeFrame: From start of IMP administration to actual Operating Room discharge (up to ~26 minutes)
measure: Time From Tracheal Extubation to Operating Room Discharge Ready
timeFrame: From tracheal extubation to Operating Room discharge ready (up to ~1 minute)
measure: Time From Tracheal Extubation to Actual Operating Room Discharge
timeFrame: From tracheal extubation to actual OR discharge (up to ~5 minutes)
measure: Time From Operating Room Discharge Ready to Post Anesthetic Care Unit (PACU) Discharge Ready
timeFrame: From Operating Room discharge ready to PACU discharge ready (up to ~33 minutes)
measure: Time From Operating Room Discharge Ready to Actual PACU Discharge
timeFrame: From Operating Room discharge ready to actual PACU discharge (up to ~4.5 hours)
measure: Time From Actual Operating Room Discharge to PACU Discharge Ready
timeFrame: From actual Operating Room discharge to PACU discharge ready (up to ~30 minutes)
measure: Time From Actual Operating Room Discharge to Actual PACU Discharge
timeFrame: From actual Operating Room discharge to actual PACU discharge (up to ~4.4 hours)
measure: Time From PACU Admit to PACU Discharge Ready
timeFrame: From PACU admit to PACU discharge ready (up to ~25 minutes)
measure: Time From PACU Admit to Actual PACU Discharge
timeFrame: From PACU admit to actual PACU discharge (up to ~4.3 hours)
Locations:
Study officials:
References:
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citation: Geldner G, Niskanen M, Laurila P, Mizikov V, Hubler M, Beck G, Rietbergen H, Nicolayenko E. A randomised controlled trial comparing sugammadex and neostigmine at different depths of neuromuscular blockade in patients undergoing laparoscopic surgery. Anaesthesia. 2012 Sep;67(9):991-8. doi: 10.1111/j.1365-2044.2012.07197.x. Epub 2012 Jun 14.