Comparison of Sugammadex With Neostigmine During Laparoscopic Cholecystectomy or Appendectomy (P05699 AM2)(COMPLETED)

• 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 [ Time Frame: From start of IMP administration to recovery of T4/T1 ratio to 0.9 (ranging from ~2 minutes to ~9 minutes) ] [ Designated as safety issue: No ]
  Neuromuscular functioning was monitored by applying repetitive Train-Of-Four (TOF) electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0) indicates the extent of recovery from neuromuscular blockade (NMB). In this study, twitch responses were recorded until the T4/T1 Ratio reached >= 0.9, the minimum acceptable ratio that indicated recovery from NMB. A faster time to recovery of the T4/T1 Ratio to 0.9 indicates a faster recovery from NMB.
  
  

• Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.7 [ Time Frame: From start of IMP administration to recovery of T4/T1 Ratio to 0.7 (ranging from ~2 minutes to ~5 minutes) ] [ Designated as safety issue: No ]
  Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0). A faster time to recovery of the T4/T1 Ratio to 0.7 indicates a faster recovery from NMB.
  
  
• Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.8 [ Time Frame: From start of IMP administration to recovery of T4/T1 Ratio to 0.8 (ranging from ~2 minutes to ~6 minutes) ] [ Designated as safety issue: No ]
  Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0). A faster time to recovery of the T4/T1 Ratio to 0.8 indicates a faster recovery from NMB.
  
  
• Number of Participants Who Experienced Pre-treatment Serious Adverse Events (SAEs) and Post-treatment SAEs [ Time Frame: From signing of informed consent to end of trial (7 days after surgery) ] [ Designated as safety issue: Yes ]

  An SAE is defined as any untoward medical occurrence that at any dose: results in death; is life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or is a congenital anomaly/birth defect.

  Participants were monitored for occurrence SAEs for up to 7 days after last dose IMP. Pre-treatment refers to the period from signing of the informed consent up to start of IMP administration. Post-treatment refers to the period from start of IMP administration to 7 days after IMP administration.

  
  
• Number of Participants Who Experienced Pre-treatment Non-serious Adverse Events (AEs) and Post-treatment Non-serious AEs [ Time Frame: From signing of informed consent to end of trial (7 days after surgery) ] [ Designated as safety issue: Yes ]
  An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body, whether or not considered related to the use of the product. Participants were monitored for occurrence AEs for up to 7 days after last dose IMP. Pre-treatment refers to the period from signing of the informed consent up to start of IMP administration. Post-treatment refers to the period from start of IMP administration to 7 days after IMP administration.
  
  

• Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.5 and 0.6 [ Time Frame: From start of IMP administration to recovery of T4/T1 Ratio to 0.5 and 0.6 (ranging from ~1 minute to ~4 minutes) ] [ Designated as safety issue: No ]
  Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0). Faster times to recovery of the T4/T1 Ratios to 0.5 and 0.6 indicate faster recoveries from NMB.
  
  
• 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 [ Time Frame: 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) ] [ Designated as safety issue: No ]
  Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0). A faster time to recovery of the T4/T1 Ratio indicates a faster recovery from NMB.
  
  
• 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 [ Time Frame: From last dose of rocuronium to 1-2 PTC (up to ~9 minutes) ] [ Designated as safety issue: No ]
  The time of 1-2 PTC refers to when 1-2 twitches are generated after tetanic stimulation. Time to 1-2 PTC is the time point of the last single twitch >0 or baseline (in case of noise or direct stimulation) within the sequence of a PTC measurement. 1-2 PTC was the target depth of NMB at which sugammadex was to be administered.
  
  
• 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 [ Time Frame: From last dose of rocuronium to reappearance of T2 (up to ~26 minutes) ] [ Designated as safety issue: No ]
  The time of reappearance of T2 refers to when the second twitch reappears after TOF stimulation. Reappearance of T2 was the target depth of NMB at which neostigmine was to be administered.
  
  
• Mean Systolic Blood Pressure [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
  Systolic Blood Pressure was measured at screening, before start of rocuronium administration, before start of IMP administration, at 2, 5, 10, 30 minutes post-IMP administration, and at the post-anesthetic visit (the day after surgery).
  
  
• Mean Diastolic Blood Pressure [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
  Diastolic Blood Pressure was measured at screening, before start of rocuronium administration, before start of IMP administration, at 2, 5, 10, 30 minutes post-IMP administration, and at the post-anesthetic visit (the day after surgery).
  
  
• Mean Heart Rate [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
  Heart Rate was measured at screening, before start of rocuronium administration, before start of IMP administration, at 2, 5, 10, 30 minutes post-IMP administration, and at the post-anesthetic visit (the day after surgery).
  
  
• Number of Participants Who Had Physical Examinations [ Time Frame: At screening (within 7 days prior to surgery) and at the post-anesthetic visit (the day after surgery) ] [ Designated as safety issue: Yes ]
  Physical examinations were to be conducted at screening (within 7 days prior to surgery) and at the post-anesthetic visit (the day after surgery).
  
  
• Number of Participants With Train-of-Four- (TOF-) Watch® SX and Arm Board Related Adverse Events [ Time Frame: From induction of anesthesia to recovery from NMB (up to ~3 hours) ] [ Designated as safety issue: Yes ]
  Events were to be collected for the entire period of neuromuscular transmission monitoring and were defined as an occurrence that resulted or could have resulted in: death; a serious deterioration in the state of health of a user; an occurrence which might, if it recurred, lead to death or serious deterioration in health; inaccuracy as well as any inadequacy in the labeling or instructions which could cause misuse or incorrect maintenance or adjustment which might lead to a death or serious deterioration in health; an examination of the medical device or the information supplied with the medical device indicated some factor with the potential for an incident involving death or serious deterioration in health; malfunction or deterioration in characteristics and/or performance of a medical device, which might lead to death, or serious deterioration in health; technical/medical recalls involving risk of death or serious deterioration in the state of health of the user.
  
  
• 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) [ Time Frame: Up to 30 minutes after IMP administration ] [ Designated as safety issue: Yes ]
  Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (heights) of the 1st and 4th twitches, respectively, after TOF stimulation. The T4/T1 Ratio is expressed as a decimal of up to 1.0. A higher ratio indicates greater recovery from NMB. A decline in the T4/T1 ratio from >=0.9 (indicating a recovery from NMB) to <0.8 for at least three consecutive TOF values was considered to be a reoccurrence of NMB.
  
  
• 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) [ Time Frame: Up to 24 hours after IMP administration ] [ Designated as safety issue: Yes ]
  Clinical evidence of reoccurrence of NMB or residual NMB was assessed by oxygen saturation (by pulse oximetry) and breath frequency measurements as per routine practice after anesthesia and neuromuscular monitoring.
  
  
• Number of Participants With Events Due to a Possible Interaction of Sugammadex With Endogenous Compounds or With Exogenous Compounds Other Than Rocuronium [ Time Frame: Up to 7 days after IMP administration ] [ Designated as safety issue: Yes ]
  Any evidence of events due to a possible interaction of sugammadex with endogenous compounds or with exogenous compounds other than rocuronium, was to be recorded.
  
  
• Monitoring of Clinical Signs of Recovery According to Routine Anesthetic Procedures at the Trial Sites [ Time Frame: Up to PACU discharge (up to ~4.5 hours) ] [ Designated as safety issue: Yes ]
  The monitoring of clinical signs of recovery was to be conducted based on the routine anesthetic procedures at each site.
  
  
• Number of Female Participants or Partners of Male Participants Who Became Pregnant During Study [ Time Frame: Up to 30 days after IMP administration ] [ Designated as safety issue: Yes ]
  Thirty days after administration of IMP, female participants of childbearing potential were asked whether they became pregnant during the trial and male participants were asked whether their partner (if of childbearing potential) became pregnant during the trial.
  
  
• Time From Operating Room Admission to Operating Room Discharge Ready [ Time Frame: From Operating Room admission to Operating Room discharge ready (up to ~3 hours) ] [ Designated as safety issue: No ]
  The time of Operating Room admission was defined as the time at which the participant was physically placed into the Operating Room. The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of ≥0.9 and the participant's wound dressing was in place.
  
  
• Time From Operating Room Admission to Actual Operating Room Discharge [ Time Frame: From Operating Room admission to actual Operating Room discharge (up to ~3 hours) ] [ Designated as safety issue: No ]
  The time of Operating Room admission was defined as the time at which the participant was physically placed into the Operating Room. The time of Operating Room discharge was defined as the actual time the participant was discharged from the Operating Room.
  
  
• Time From Operating Room Discharge Ready to Actual Operating Room Discharge [ Time Frame: From Operating Room discharge ready to actual Operating Room discharge (up to ~5 minutes) ] [ Designated as safety issue: No ]
  The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of >=0.9 and the participant's wound dressing was in place. The time of Operating Room discharge was defined as the actual time the participant was discharged from the Operating Room.
  
  
• 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 [ Time Frame: From start of IMP administration to recovery of the T4/T1 ratio to the designated value (ranging from ~1 minute to ~10 minutes) ] [ Designated as safety issue: No ]
  The time of IMP administration was defined as the actual time at which IMP administration was started.
  
  
• Time From Start of IMP Administration to Tracheal Extubation [ Time Frame: From start of IMP administration to tracheal extubation (up to ~21 minutes) ] [ Designated as safety issue: No ]
  The time of IMP administration was defined as the actual time at which IMP administration was started. The time of tracheal extubation was defined as the actual time at which the participant was extubated.
  
  
• Time From Start of IMP Administration to Operating Room Discharge Ready [ Time Frame: From start of IMP administration to Operating Room discharge ready (up to ~21 minutes) ] [ Designated as safety issue: No ]
  The time of IMP administration was defined as the actual time at which IMP administration was started. The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of >=0.9 and the participant's wound dressing was in place.
  
  
• Time From Start of IMP Administration to Actual Operating Room Discharge [ Time Frame: From start of IMP administration to actual Operating Room discharge (up to ~26 minutes) ] [ Designated as safety issue: No ]
  The time of IMP administration was defined as the actual time at which IMP administration was started. The time of Operating Room discharge was defined as the actual time at which the participant was discharged from the Operating Room.
  
  
• Time From Tracheal Extubation to Operating Room Discharge Ready [ Time Frame: From tracheal extubation to Operating Room discharge ready (up to ~1 minute) ] [ Designated as safety issue: No ]
  The time of tracheal extubation was defined as the actual time at which the participant was extubated. The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of >=0.9 and the participant's wound dressing was in place.
  
  
• Time From Tracheal Extubation to Actual Operating Room Discharge [ Time Frame: From tracheal extubation to actual OR discharge (up to ~5 minutes) ] [ Designated as safety issue: No ]
  The time of tracheal extubation was defined as the actual time at which the participant was extubated. The time of Operating Room discharge was defined as the actual time at which the participant was discharged from the Operating Room.
  
  
• Time From Operating Room Discharge Ready to Post Anesthetic Care Unit (PACU) Discharge Ready [ Time Frame: From Operating Room discharge ready to PACU discharge ready (up to ~33 minutes) ] [ Designated as safety issue: No ]
  The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of >=0.9 and the participant's wound dressing was in place. The time of PACU discharge ready was defined as the time at which the participant had a Modified Aldrete Score >=9. The Modified Aldrete Score was to be assessed at PACU arrival, at 5, 15, 30, 45, 60 minutes after PACU arrival and every 15 minutes thereafter (if applicable) until the participant was ready to be discharged from the PACU. The Modified Aldrete Postoperative Recovery Score (range = 0-10) is calculated based on scores of 0 to 2 each for Activity, Respiration, Circulation, Consciousness and Oxygen Saturation, with a higher score indicating increased postoperative recovery.
  
  
• Time From Operating Room Discharge Ready to Actual PACU Discharge [ Time Frame: From Operating Room discharge ready to actual PACU discharge (up to ~4.5 hours) ] [ Designated as safety issue: No ]
  The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of >=0.9 and the participant's wound dressing was in place. The time of PACU discharge was defined as the actual time the participant was discharged from the PACU.
  
  
• Time From Actual Operating Room Discharge to PACU Discharge Ready [ Time Frame: From actual Operating Room discharge to PACU discharge ready (up to ~30 minutes) ] [ Designated as safety issue: No ]
  The time of Operating Room discharge was defined as the actual time the participant was discharged from the Operating Room. The time of PACU discharge ready was defined as the time at which the participant had a Modified Aldrete Score >=9. The Modified Aldrete Score was to be assessed at PACU arrival, at 5, 15, 30, 45, 60 minutes after PACU arrival and every 15 minutes thereafter (if applicable) until the participant was ready to be discharged from the PACU. The Modified Aldrete Postoperative Recovery Score (range = 0-10) is calculated based on scores of 0 to 2 each for Activity, Respiration, Circulation, Consciousness and Oxygen Saturation, with a higher score indicating increased postoperative recovery.
  
  
• Time From Actual Operating Room Discharge to Actual PACU Discharge [ Time Frame: From actual Operating Room discharge to actual PACU discharge (up to ~4.4 hours) ] [ Designated as safety issue: No ]
  The time of Operating Room discharge was defined as the actual time the participant was discharged from the Operating Room. The time of PACU discharge was defined as the actual time the participant was discharged from the PACU.
  
  
• Time From PACU Admit to PACU Discharge Ready [ Time Frame: From PACU admit to PACU discharge ready (up to ~25 minutes) ] [ Designated as safety issue: No ]
  The time of PACU admit was defined as the actual time the participant was admitted to the PACU. The time of PACU discharge ready was defined as the time at which the participant had a Modified Aldrete Score >=9. The Modified Aldrete Score was to be assessed at PACU arrival, at 5, 15, 30, 45, 60 minutes after PACU arrival and every 15 minutes thereafter (if applicable) until the participant was ready to be discharged from the PACU. The Modified Aldrete Postoperative Recovery Score (range = 0-10) is calculated based on scores of 0 to 2 each for Activity, Respiration, Circulation, Consciousness and Oxygen Saturation, with a higher score indicating increased postoperative recovery.
  
  
• Time From PACU Admit to Actual PACU Discharge [ Time Frame: From PACU admit to actual PACU discharge (up to ~4.3 hours) ] [ Designated as safety issue: No ]
  The time of PACU admit was defined as the actual time the participant was admitted to the PACU. The time of PACU discharge was defined as the actual time the participant was discharged from the PACU.
  
  

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.