Clinical trial NCT03276026
Conditions: Postoperative Nausea and Vomiting Respiratory Conditions Due to Other External Agents
Keywords: sugammadex post anesthesia care unit recovery
Sponsor: Virtua Health, Inc.
Start date: 2018-02-12; Completion date: 2018-11-08
Enrollment: 68 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The investigators will track bariatric patients who received sugammadex versus neostigmine in the post anesthesia care unit until discharge and assess their length of stay and possible nausea / vomiting / hypoxia episodes.

Detailed description:
During their preadmission testing, patients planning to undergo sleeve gastrectomy bariatric surgeries will be consented (by having them sign consent forms) and recruited for the study. A trained individual will track these patients after the surgery in the post anesthesia care unit until discharge and assess their length of stay and possible nausea / vomiting. The exact time the investigators are looking to assess is patient arrival to the post anesthesia care unit until patient ready for discharge when the anesthesiologist writes the anesthesia evaluation. The time the reversal agent is administered during the start of skin closure until patient medically ready to leave the post anesthesia care unit will also be taken into account. Blinded to the treatment group, the trained individual will ask each patient every 15 minutes after arrival to the post anesthesia care unit if they are experiencing nausea or vomiting. As an exploratory measure, the trained individual will assess the patient at these same times (every 15 minutes) and determine their oxygen saturation. The investigators will take all the data from the observations and use statistical means to measure what is significant. A discussion and conclusion will follow. Finally, the principal investigator will submit the study outcomes to an anesthesia journal.

Arms: arm 1: The control group will be the 63 patients who receive Neostigmine in a dose of 5mg, along with the anti-cholinergic glycopyrrolate 0.6mg. arm 2: 63 patients will be given Sugammadex in a dose of 2mg/kg if the train of four twitch count is 2 and 4mg/kg if the twitch response has reached 1-2 post-tetanic counts with no twitch response to train of four.
Interventions: intervention 1: Sugammadex intervention 2: Neostigmine
Intervention descriptions: intervention 1: Sugammadex is used for the reversal of neuromuscular block in surgery that requires deep blockade to facilitate surgical procedures. intervention 2: Neostigmine is used for the reversal of neuromuscular block in surgery that requires deep blockade to facilitate surgical procedures.

Protocol documents:
Prot_SAP_000.pdf: 
      MISP Template: Protocol 
1 
Final Version: 01/29/2018 
 
 
 
IInnvveessttiiggaattoorr  SSttuuddiieess  PPrrooggrraam
m  ((M
MIISSPP))  
PPrroottooccooll  TTeem
mppllaattee  
 
Requirements for Submitting a Full Proposal 
 
 
Section #1 - MISP Protocol Identification 
 
Study Title: 
  
The title of the protocol should include study design, indication and, where applicable, dosage, 
dosage form, and comparative agent(s). 
 
A randomized prospective study to compare the effectiveness of Neostigmine versus 
Sugammadex in length of PACU stay in ASA II and III patients undergoing sleeve gastrectomy 
bariatric surgery 
 
Request Date: 
 
May 1  
Institution Name 
 
Virtua Memorial Hospital 
Investigator 
Contact 
Information: 
- Full address  
- Phone No. 
- Fax  No. 
- e-mail address 
 
 
Adam Thaler 
175 Madison Ave. 
Mount Holly, NJ 08060 
609-914-8744 
athaler@virtua.org 
 
 
 
 


      MISP Template: Protocol 
2 
Final Version: 01/29/2018 
 
 
Section #2- Core Protocol 
 
2.1 Objectives & 
Hypotheses  
 
 
 
 
2.1 List the objectives.  
 
Objective 1: Determine the difference in length of PACU stay from PACU arrival until 
ready for PACU discharge for ASA II and III patients reversed with Sugammadex 
versus Neostigmine in sleeve gastrectomy surgeries.  
 
Objective 2: Assess the incidence of PONV in ASA II and III patients reversed with 
Sugammadex versus Neostigmine, with the prediction that there will be a lower 
incidence of PONV in the Sugammadex group.  
 
Objective 3: Assess the incidence of respiratory complications postoperatively 
specifically looking at oxygen saturation at 10 minutes after patient arrival to PACU 
and 60 minutes after arrival to PACU and any intervention necessary.  
 
2.1.1 List the clinical hypotheses.  
 
The main hypothesis is that Sugammadex given to reverse non-depolarizing muscle 
relaxants will expedite patients having bariatric surgery out of the PACU  
 
Bariatric patients receiving Sugammadex will have less PONV due to the fact that an 
adverse effect of Neostigmine is nausea and/or vomiting. 
 
Patients’ status post sleeve gastrectomy surgeries who receive sugammadex will 
have less respiratory complications than their counterparts who receive neostigmine 
and thus show a higher PACU oxygen saturation since sugammadex binds and 
reverses the non-depolarizer muscle relaxants more effectively.  
 
t2.2 Background & 
Rationale, 
Significance of 
Selected Topic & 
Preliminary Data  
 
Sugammadex has been demonstrated to shorten the time to reach a train-of-four ratio of 0.9 
as well as the extubation time, resulting in improvement of operating room turnover in 
clinical anesthesia settings, including neuromuscular monitoring. 
Sugammadex may be recommended for the reversal of neuromuscular block in surgery that 
requires deep blockade to facilitate surgical procedures. From this point of view, bariatric 
surgery meets the indications for sugammadex use. Therefore, we frequently use this agent 
for the reversal of neuromuscular block in sleeve gastrectomy’s, duodenal switches, and 
gastric bypasses. 
We aimed to investigate whether sugammadex shortens recovery time in the PACU. 
Currently the average length of stay for our sleeve gastrectomy’s performed by one of our 
bariatric surgeons, Dr. Wasser, is 112 minutes over the last 17 months for ASA II and III 
patients.  A secondary endpoint we want to measure is the incidence in postoperative nausea 
and vomiting with Sugammadex as compared to neostigmine. We hypothesize that 
sugammadex will shorten PACU recovery time, and that it will reduce PONV in patients 
undergoing sleeve gastrectomy bariatric surgeries. 
Morbid obese population is increasing every year worldwide, and laparoscopic bariatric 
surgery has a central role in their treatment. The postoperative period of these patients is not 
free from complications. The introduction of sugammadex has brought huge developments in 
patient's safety and now laparoscopic sleeve gastrectomy surgery is performed with better 
care and quality 


      MISP Template: Protocol 
3 
Final Version: 01/29/2018 
The rationale for conducting this study is to show that Sugammadex is more effective than 
Neostigmine in reversing non-depolarizing muscle relaxants. This will be demonstrated by 
the shorter ready for PACU discharge time leading to less cost. It will also show that there 
will be less post-operative respiratory complications in the Sugammadex group, including but 
not limited to PONV.  
 
A study by Park ES in the BMC Anesthesiology showed that sugammadex can shorten 
anesthesia and extubation times as well as recovery time in the PACU and reduce 
postoperative hemodynamic complications in a clinical setting in the absence of 
neuromuscular monitoring. This may enhance the patients’ recovery in the OR and PACU 
while improving the postoperative condition of patients (1). Sugammadex has been 
demonstrated to decrease the incidence of post-operative respiratory complications and 
related costs in patients with OSA. After extubation, desaturation which is defined as spO2 
<90% was observed in 32.4% of the neostigmine group and in 10.8% in the sugammadex 
group (2). It was also shown that patient receiving sugammadex over neostigmine had a 
shorter PACU stay (2). A comparison of sugammadex and neostigmine in children for 
reversal of rocuronium-induced neuromuscular blockade in children demonstrated a faster 
recovery and extubation times and lower incidence of adverse events compared with 
neostigmine (5). 
 
Sugammadex has been associated with less PONV and a faster discharge from the PACU in 
laparoscopic bariatric surgeries. In the first hour postoperatively, 27% of patients in the 
neostigmine group had PONV versus only 8% in the sugammadex group were observed to 
have nausea and/or vomiting (3). A retrospective investigation of postoperative outcome after 
reversal of residual neuromuscular blockade in the Eur J Anaesthesiol showed that 
neuromuscular blockade reversal with sugammadex was associated with lowest rate of 
PONV and may reduce the risk of pulmonary complications in elderly ASA 3/4 patients (4). 
 
2.3 Study Design 
 
The study is a randomized, interventional, controlled, blinded, single center study. 
There will be a minimum of 126 study patients, with 63 patients in the neostigmine 
group and 63 patients in the Sugammadex group.  
Inclusion criteria: 
 
Patients having sleeve gastrectomy 
 
Surgeries performed by Dr. Sam Wasser 
 
BMI >35  
 
ASA II and III patients 
 
+/- hiatal hernia repairs with the sleeve gastectomy 
Exclusion criteria: 
 
Patients having a different type of bariatric surgery including but not limited 
to duodenal switch, gastric bypass, hand-assisted laparoscopic sleeve 
gastrectomy 
 
Sleeve gastrectomy’s performed by other surgeons than Dr. Sam Wasser. 
 
Pregnancy 
 
Allergic to sugammadex, Zofran or scopolamine 
 
COPD or Asthma that is uncontrolled 
 
ASA I, IV, V patients 
Primary parameter: 
 
Assess the difference in length of PACU stay from PACU arrival until 
medically ready for PACU discharge and also from time of administration of 
reversal agent (which will be start of skin closure) until medically ready for 
PACU discharge 
Secondary parameter: 
 
Assess the incidence of PONV in patients by asking the patients every 15 
minutes after arrival to PACU if they are having nausea or vomiting 
Exploratory parameter: 


      MISP Template: Protocol 
4 
Final Version: 01/29/2018 
 
Assess the incidence of respiratory complications postoperatively looking at 
oxygen saturation every 15 minutes after PACU arrival and any intervention 
necessary 
2.4 Study Flowchart 
 
The bariatric surgeon, Dr. Sam Wasser, has already agreed to have their patients in 
the study. The next step is to get IRB approval. The patients will be consented prior 
to surgery and their signed consents would be kept in our study records. We will 
track these patients after the surgery in the PACU until discharge and assess their 
length of stay and possible nausea / vomiting. The exact time we are looking for is 
patient arrival to PACU until patient ready for discharge when the anesthesiologist 
writes the anesthesia evaluation. We will also take into account the time the reversal 
agent is administered during the start of skin closure until patient medically ready to 
leave the PACU. Blinded to the treatment group, an individual will ask each patient 
every 15 minutes after arrival to PACU if they are experiencing nausea or vomiting. 
As an exploratory measure, we will assess the patient at these same times (every 15 
minutes) and determine their oxygen saturation. Then we will take all the results and 
use statistical means to measure what is significant. A discussion and conclusion will 
follow. Finally I will submit this to an anesthesia journal.   
 
2.5 Study 
Procedures 
The initial screening period will identify the patients that fit in the inclusion criteria 
and get their consent to be in the study. There will be two measurements of length of 
time to assess. One measurement will be from the time the reversal agent is 
administered which will be the start of skin closure to the patient ready for discharge 
from the PACU. The second duration of treatment will be the patients' stay in the 
PACU from arrival from the operating room until ready for discharge based on 
anesthesia evaluation completed. The criteria for readiness for discharge are based 
on a modified Aldrete Score >8. The assessor will be blinded to the study group. 
Readiness will be assessed every 5 minutes. The control group will be the patients 
who receive the Neostigmine in a dose of 5mg, along with the anti-cholingeric 
Glycopyrolate 0.6mg. Sugammadex will be given in a dose of 2mg/kg if the train of 
four twitch count is 2 and 4mg/kg if the twitch response has reached 1-2 post-tetanic 
counts with no twitch response to train of four. Monitoring neuromuscular response 
will be with the device SunStim Plus by SunMed. The end point when we will give 
the reversal agent is a T1 or T2 block of the adductor policis muscle on the twitch 
monitor. Our standard criteria for extubation include full reversal of muscle relaxation 
with sustained tetany and a TOF ratio of > .9. We also require adequate oxygenation 
SpO2>92%, adequate ventilation with tidal volumes >5 ml/kg, spontaneous RR 
>7bpm, and the patient to be hemodynamically stable. All patients in both the control 
and study group will receive a Scopolamine 1.5mg patch instructed to place behind 
the ear the night prior to coming in for surgery and Ondansetron 4mg given 30 
minutes prior to the end of the surgery. . All patients will be induced with the 
standard medications of Lidocaine, Fentanyl, Propofol and Rocuronium unless 
clinically indicated. The patients will be standardized to receive the volatile 
anesthetic Sevoflurane. Nitrous Oxide will not be given to any patient since this can 
increase the likelihood of PONV. From a pain management standpoint, fentanyl and 
hydromorphone will be administered intraoperatively based on the patient’s 
requirements at the discretion of the anesthesia team. The standard inflation 
pressure at our institution is 18mmHg. The surgeon makes a judicious effort to 
remove CO2 at the end of the surgery as well to help this cause because residual 
CO2 can lead a patient to have nausea.  The individual who assesses the PONV in 
the PACU will do so at q 15 minute intervals when VS are checked. They will be 
blinded to neostigmine and sugammadex treatment.  If the patient has PONV, the 
RN will administer Ondansetron 4mg. If the patient still has PONV then they will 
administer 25 mg of Diphenhydramine and a third option would be Promethazine 
12.5 mg.  
 


      MISP Template: Protocol 
5 
Final Version: 01/29/2018 
2.6 Study Duration 
At our institution Dr. Sam Wasser currently averages about 13 ASA II and III sleeve 
gastrectomy bariatric surgeries a month. We therefore anticipate that it will take 
approximately 10 months for patient recruitment and study completion. 
2.7 Statistical 
Analysis and 
Sample Size 
Justification  
Both a statistician and I will be responsible for analyzing the study data. The PONV 
data will be blinded, with the individual(s) responsible for asking the patient if they’re 
experiencing nausea not made aware of which reversal agent was given.  
Variables/Time Points of Interest 
 
The assessment of PONV: 
 
A blinded individual will ask patients at 15 minute intervals in the PACU after 
arrival to the recovery room until ready for discharge 
 
It will be a check box with yes and no being the only outcome.  
 
If the patient has PONV at any point in the PACU it is considered positive for 
PONV. 
The assessment of time spent in the PACU: 
 
Defined as the time from arrival in PACU to ready for PACU discharge 
(Anesthesia Evaluation completed). The other time measurement is from 
administration of the reversal agent during the start of skin closure to the 
patient being ready for PACU discharge.  
Cost Analysis 
 
Knowing the cost per 30 minute increment after the first hour stay in the 
PACU Phase 1 is $59.32, the prediction of a 15 minute decrease in PACU 
stay will equate to a cost savings of approximately $30/patient in time spent 
in the PACU 
 
 
Statistical Methods 
 
The primary outcome measure is the difference in mean PACU Phase 1 LOS 
minutes between the two groups for which the two sample t-test will be utilized. 
While the historical (January 2016 to May 2017) PACU Phase 1 LOS (minutes) data 
did not appear to follow a normal distribution (P-Value = 0.005), they were however 
found to be lognormally distributed (P-Value = 0.123) [see appendix]. The t-test will 
therefore be conducted using the log-transformed data. A two sample t-test on the 
log-transformed PACU data showed that there was no significant difference in 
geometric mean PACU LOS between ASA II (101.19 minutes) and III (109.62 
minutes) patients (P-Value = 0.131). We therefore find it reasonable to include ASA 
II and III patients in the study.  
The secondary analysis will use the z-test for proportions since we are looking at the 
percentages of PONV “yes” outcomes. The exploratory parameter analysis will use 
the z-test for proportions since we are looking at the percentages of post op 
respiratory “yes” outcomes. 
 
Power/Sample Size: 
 
Based on an 80% power to detect a 15% difference in PACU LOS minutes between 
the two groups and a standard deviation of 0.2634 for the log-transformed data, a 
minimum sample size of 57 patients per group is needed. Applying a 10% markup 
against the derived minimum sample size, we will enroll a minimum of 63 patients in 
each group for a total of 126 study patients. 
A documented study in the literature (3) revealed that in the first hour 
postoperatively, 27% of patients in the neostigmine group had PONV versus 8% in 
the sugammadex group. According to another study (2), after extubation, 
desaturation (spO2<90%) was observed in 32.4% of the neostigmine group versus 
10.8% in the sugammadex group. With 63 patients in each study group, statistical 


      MISP Template: Protocol 
6 
Final Version: 01/29/2018 
powers of 80.9% and 84.7% are estimated for the PONV test and respiratory 
complications test respectively.  
2.8 Specific Drug 
Supply 
Requirements  
 
 
For US and non-US studies, the investigator will be responsible for the destruction of 
the supplies at the study center pursuant to the ICH/GCP Guidelines, local 
regulations and the investigator’s institutional policies. Clinical supplies must be 
received by a designated person at the study site, handled and stored safely and 
properly, and kept in a secured location to which only the investigator and 
designated assistants have access. Clinical supplies are dispensed in accordance 
with the protocol. The investigator is responsible for keeping accurate records of the 
clinical supplies, the amount dispensed to and returned by the patients, and the 
disposition at the end of the study. 
 
2.9 Adverse 
Experience 
Reporting 
The study agreement outlines the requirement for adverse experience reporting.  For 
clinical protocols, specific adverse experience reporting requirements must be 
identified in the protocol if the Model Study Agreement is not used (in general, this 
would apply to non-US. studies whose local requirements may prohibit the use of the 
agreement).  
2.10 Itemized Study 
Budget  
 
Please refer to the Budget spreadsheet for specifics.   
 
2.11 References 
 
1. Park ES, Lim BG, Lee WJ, Lee IO. Sugammadex facilitates early recovery after surgery even in the absence of 
neuromuscular monitoring in patients undergoing laryngeal microsurgery: a single-center retrospective study. 
BMC Anesthesiol. 2016 Aug 2;16(1):48.  
2. Ünal DY, Baran İ, Mutlu M, Ural G, Akkaya T, Özlü O. Comparison of Sugammadex versus Neostigmine Costs 
and Respiratory Complications in Patients with Obstructive Sleep Apnoea. Turk J Anaesthesiol Reanim. 2015 
Dec;43(6):387-95. doi: 10.5152/TJAR.2015.35682. Epub 2015 Dec 1 
3. Castro DS Jr, Leão P, Borges S, Gomes L, Pacheco M, Figueiredo P. Sugammadex reduces postoperative pain 
after laparoscopic bariatric surgery: a randomized trial. Surg Laparosc Endosc Percutan Tech. 2014 Oct;24(5):420-3. 
4. Ledowski T, Falke L, Johnston F, Gillies E, Greenaway M, De Mel A, Tiong WS, Phillips M. Retrospective 
investigation of postoperative outcome after reversal of residual neuromuscular blockade: sugammadex, neostigmine 
or no reversal. Eur J Anaesthesiol. 2014 Aug;31(8):423-9.  
5. Ammar AS, Mahmoud KM, Kasemy ZA. A comparison of sugammadex and neostigmine for reversal of 
rocuronium-induced neuromuscular blockade in children. Acta Anaesthesiol Scand. 2017 Apr;61(4):374-380. 
 
2.12 Publication 
Plan 
I plan on submitting to the Journal of Clinical Anesthesia. I would not be opposed to 
other suggestions for publication.  
Projected date of submission would be December 2018 time frame.  
I would also submit an abstract to the ASA and hopefully present my results at the 
national meeting. 
 
2.13 Curriculum 
Vitae 
 
Investigator should provide curriculum vitae in English and a listing of references to MSD. 
2.13 Protocol 
Submission for 
Investigator-
Initiated Studies  
U.S. protocols should be submitted by US investigators directly or through the Global 
Research Specialist at  www.merckiisp.com   
 
Non U.S. protocols should be submitted to the MSD office by the investigators. 


      MISP Template: Protocol 
7 
Final Version: 01/29/2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix: A randomized prospective study to compare the effectiveness of Neostigmine versus 
Sugammadex in length of PACU stay in ASA II and III patients undergoing sleeve gastrectomy bariatric 
surgery 
Jan 2016 to May 2017 PACU Data for Dr S. Wasser’s Lscopic Gastrectomy Sleeve Cases  


      MISP Template: Protocol 
8 
Final Version: 01/29/2018