Randomized Controlled Assessor Blinded Clinical Trial of Sugammadex Versus Neostigmine /Glycopyrrolate for Reversal of Rocuronium Induced Neuromuscular Blockade: Time to Discharge From Post Anesthesia Care Unit and Patient Satisfaction With Recovery
Phase: PHASE3
Conditions: Surgery
Sponsor: Memorial Sloan Kettering Cancer Center

Memorial Sloan Kettering Cancer Center 
IRB Number: 17-207 A(7) 
Approval date: 17-Jul-2019 
Page 1 of 27 
 
 
 
 
 
 
 
 
Randomized Controlled Assessor Blinded Clinical Trial of Sugammadex versus 
Neostigmine/Glycopyrrolate for Reversal of Rocuronium Induced Neuromuscular 
Blockade: Time to Discharge From Post Anesthesia Care Unit and Assessment of 
NMB Recovery 
 
Principal 
Investigator/Department: 
German Echeverry, MD 
Anesthesiology and CCM 
Co-Principal 
Investigator(s)/Department: 
Florence Grant, MD 
Luis Tollinche, MD 
Cindy Yeoh, MD 
Anesthesiology and CCM 
Anesthesiology and CCM 
Anesthesiology and CCM 
Investigator(s)/Department: 
Gregory W. Fischer, MD 
Dawn Desiderio, MD 
William Marx, MD 
Kay See Tan, PhD 
Garrett Nash, MD 
Paul Russo, MD 
Yukio Sonoda, MD 
Oliver Zivanovic,  MD 
Peter Allen, MD 
Meghan Decker, NP 
Megan Abate, NP 
Omotara Adewale, NP 
Jennifer Aviado-Langer,  NP 
Maria Cantos, NP 
Laura Conti-Harrigan, NP 
Alison Costalos, NP 
Stacey Cuomo, NP 
Leslie Eadon Blades, NP 
Danielle Escaleira, NP 
Glenda Espinosa, NP 
Chakia Faniel, NP 
Christine Ferrari, NP 
Evlyn Hinds, NP 
Laura James, NP 
Stacey Kaufman, NP 
Kenny Lacossiere, NP 
John Lezoli, NP 
Marie Helene Lofland, NP 
Margaret McSweeney, NP 
Rosemary Ortiz, NP 
Dilnoza Portnoy, NP 
Gina Prior, NP 
Celeste Springer, NP 
Margaret Smith, NP 
Anesthesiology and CCM 
Anesthesiology and CCM 
Anesthesiology and CCM 
Epidemiology/Biostatistics 
Surgery/Colorectal 
Surgery/Urology 
Surgery/ Gynecology– Manhattan  & West Harrison 
Surgery/ Gynecology – Manhattan  & Commack 
Surgery/ HPB 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
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Nursing 

Page 2 of 27 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
gy and CCM 
gy and CCM 
gy and CCM 
gy and CCM 
Memorial Sloan Kettering Cancer 
Center IRB Number: 17-207 A(7) 
Approval date: 17-Jul-2019 
Theresa Hall, NP 
Nursing 
Laryn Cullen, NP 
Nursing 
Rebecca Repetti, NP 
Nursing 
Victoria Tague,NP 
Nursing 
Elizabeth Polcha, NP 
Nursing 
Deidre Stiehler, NP 
Nursing 
Ewa Chauvin, NP 
Nursing 
So Kim, NP 
Nursing 
Oksana Ditwell, NP 
Nursing 
Lauren Picarde, NP 
Nursing 
Anahita Dabo-Trubelja, MD 
Anesthesiolo 
Cosmin Gauran, MD 
Anesthesiolo 
Roger Padilla, MD 
Anesthesiolo 
Monique James, MD 
Anesthesiolo 
Patricia Spellman, RN 
Nursing 
Natalie Kostelecky, RN 
Nursing 
Sera Senturk, NP 
Nursing 
Christine Gillins, RN 
Nursing 
Lily Polskin, RN 
Nursing 
Consenting 
Professional(s)/Department: 
German Echeverry, MD 
Anesthesiology and CCM 
Florence Grant, MD 
Anesthesiology and CCM 
Luis Tollinche, MD 
Anesthesiology and CCM 
Cindy Yeoh, MD 
Anesthesiology and CCM 
Gregory W. Fischer, MD 
Anesthesiology and CCM 
Dawn Desiderio, MD 
Anesthesiology and CCM 
William Marx, MD 
Anesthesiology and CCM 
Garrett Nash, MD 
Surgery/Colorectal 
Paul Russo, MD 
Surgery/Urology 
Yukio Sonoda, MD 
Surgery/ Gynecology– Manhattan  & West Harrison 
Oliver Zivanovic,  MD 
Surgery/ Gynecology– Manhattan  & Commack 
Peter Allen, MD 
Surgery/ HPB 
Nancy Collado, NP 
Nursing 
Meghan Decker, NP 
Nursing 
Megan Abate, NP 
Nursing 
Omotara Adewale, NP 
Nursing 
Jennifer Aviado-Langer, NP Nursing 
Maria Cantos, NP 
Nursing 
Laura Conti-Harrigan, NP  Nursing 
Alison Costalos, NP 
Nursing 
Stacey Cuomo, NP 
Nursing 
Leslie Eadon Blades, NP Nursing 
Danielle Escaleira, NP 
Nursing 
Glenda Espinosa, NP 
Nursing 
Chakia Faniel, NP 
Nursing 
Christine Ferrari, NP 
Nursing 
Evlyn Hinds, NP 
Nursing 
Laura James, NP 
Nursing 

Page 3 of 27 
Memorial Sloan Kettering Cancer Center 
IRB Number: 17-207 A(7) 
Approval date: 17-Jul-2019 
 
 
 
 
 
Stacey Kaufman, NP 
Kenny Lacossiere, NP 
John Lezoli, NP 
Marie Helene Lofland, NP 
Margaret McSweeney, NP 
Rosemary Ortiz, NP 
Dilnoza Portnoy, NP 
Gina Prior, NP 
Celeste Springer, NP 
Margaret Smith, NP 
Theresa Hall, NP 
Laryn Cullen, NP 
Rebecca Repetti, NP 
Victoria Tague, NP 
Elizabeth Polcha, NP 
Deidre Stiehler, NP 
Ewa Chauvin, NP  
So Kim, NP 
Oksana Ditwell, NP 
Lauren Picarde, NP 
Anahita Dabo-Trubelja, MD 
Cosmin Gauran, MD 
Roger Padilla, MD 
Monique James, MD 
Sera Senturk, NP 
 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Anesthesiology and CCM 
Anesthesiology and CCM 
Anesthesiology and CCM 
Anesthesiology and CCM 
Nursing 
 
 
 
Please Note: A Consenting Professional must have completed the mandatory Human 
Subjects Education and Certification Program. 
 
 
OneMSK Sites 
Manhattan 
Westchester (consent only) 
Basking Ridge (consent only) 
Commack (consent only) 

Page 4 of 27 
Memorial Sloan Kettering Cancer Center 
IRB Number: 17-207 A(7) 
Approval date: 17-Jul-2019 
 
 
 
 
Memorial Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 

Memorial Sloan Kettering Cancer Center 
IRB Number: 17-207 A(7) 
Approval date: 17-Jul-2019 
Page 5 of 27 
 
 
 
 
Table of Contents 
1.0 
PROTOCOL SUMMARY AND/OR SCHEMA ...................................................................... 6 
2.0 
OBJECTIVES AND SCIENTIFIC AIMS ............................................................................... 8 
3.0 
BACKGROUND AND RATIONALE ..................................................................................... 8 
4.0 
OVERVIEW OF STUDY DESIGN/INTERVENTION ................................................................. 10 
4.1 Design ................................................................................................................................ 10 
4.2 Intervention .............................................................................................................................. 11 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS ........................................................................... 12 
6.0 
CRITERIA FOR SUBJECT ELIGIBILITY .............................................................................. 13 
6.1 Subject Inclusion Criteria .................................................................................................... 13 
6.2 Subject Exclusion Criteria ................................................................................................... 13 
7.0 
RECRUITMENT PLAN ................................................................................................................... 13 
8.0 
PRETREATMENT EVALUATION ...................................................................................... 14 
9.0 
TREATMENT/INTERVENTION PLAN ............................................................................... 15 
10.0 
EVALUATION DURING TREATMENT/INTERVENTION .................................................... 16 
11.0 
TOXICITIES/SIDE EFFECTS .................................................................................................... 17 
12.0 
CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT ........................ 18 
13.0 
CRITERIA FOR REMOVAL FROM STUDY ....................................................................... 18 
14.0 
BIOSTATISTICS ............................................................................................................... 18 
15.0 
RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION PROCEDURES21 
15.1 Research Participant Registration ......................................................................................... 21 
15.2 
Randomization ................................................................................................................... 21 
16.0 
DAT A M ANAGEMENT ISSUES ........................................................................................ 21 
16.1 
Quality Assurance ........................................................................................................ 22 
16.2 
Data and Safety Monitoring .............................................................................................. 22 
17.0 
PROTECTION OF HUMAN SUBJECTS ............................................................................ 22 
17.1 
Privacy .......................................................................................................................... 23 
17.2 
Serious Adverse Event (SAE) Reporting ......................................................................... 23 
17.2.1.........................................................................................................................................24 
18.0 
INFORMED CONSENT PROCEDURES .................................................................................. 24 
19.0 
REFERENCES ...................................................................................................................... 25 
20.0 
APPENDICES ................................................................................................................... 27 

Memorial Sloan Kettering Cancer Center 
IRB Number: 17-207 A(7) 
Approval date: 17-Jul-2019 
Page 6 of 27 
 
 
 
 
1.1 
PROTOCOL SUMMARY AND/OR SCHEMA 
 
Study Title: Randomized Controlled Assessor Blinded Clinical Trial of Sugammadex versus 
Neostigmine/Glycopyrrolate for Reversal of Rocuronium Induced Neuromuscular Blockade: 
Time to Discharge From Post Anesthesia Care Unit and Assessment of NMB Recovery 
 
Objectives: 
 
1) To compare the difference in duration from administration of NMB reversal agent to the 
time the patient is ready for discharge from PACU after NMB reversal with sugammadex 
versus neostigmine. 
2) To measure the quality of recovery from anesthesia and NMB and subjective patient 
assessment after reversal with SUG or NEO. 
3) To compare the differences in costs in PACU stay associated with the use of each drug. 
 
Patient Population: Patients greater than or equal to 18 years of age scheduled to undergo 
moderate length surgeries (scheduled for < 6 hours) requiring neuromuscular blockade. 
 
Design: Prospective randomized controlled assessor blinded trial. 
 
Treatment Plan: Patients will be randomized to receive either SUG or NEO NMB reversal 
after rocuronium (ROC) induced muscle paralysis at the conclusion of their surgical 
procedure. They will be assessed for time to ready to discharge from PACU, difficulty with 
breathing, the presence of diplopia or other visual disturbances, difficulty speaking, difficulty 
swallowing, the presence of nausea or vomiting, the presence of pain, feeling worried or 
anxious (all indicators of post operative muscle weakness) and muscle strength at the biceps 
brachii muscle (Oxford Scale, Appendix 1) 
 
Time to Completion: We will need to accrue 202 patients and expect the study to be 
completed and reported within 1- 2 years. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 17-207 A(7) 
Approval date: 17-Jul-2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 7 of 27 
Patient Transferred to PACU Where 
Data is Collected by Blinded Assessor 
at 30, 60 and 120 minutes after arrival 
Patient Transferred to PACU  Where 
Data is Collected by Blinded Assessor 
at 30, 60 and 120 minutes after arrival 
Time from Reversal to TOF 4/4 without 
fade 
Time from Reversal to Extubation 
Recorded 
NMB Reversed at End of Case with 
Neostigmine 0.05mg/kg (max5mg) and 
Glycopyrrolate 0.01mg/kg 
NMB Reversed at End of Case with 
Sugammadex 2mg/kg 
During Surgery NMB is 
Maintained  at 1-2 Twitches 
During Surgery NMB is 
Maintained at 1-2 Twitches 
Randomized to Reversal with 
Neostigmine/Glycopyrrolate 
Randomized to Reversal with 
Sugammadex 
Patients Assessed and Consented in 
Surgical Clinic or PST 
Time from Admission to PACU to Ready 
to Discharge from PACU Recorded 
Time from Admission to PACU to Ready 
to Discharge from PACU Recorded 
Time from Reversal to TOF 4/4 without 
fade 
Time from Reversal to Extubation 
Recorded 

Memorial Sloan Kettering Cancer Center 
IRB Number: 17-207 A(7) 
Approval date: 17-Jul-2019 
Page 8 of 27 
 
 
 
 
2.1 
OBJECTIVES AND SCIENTIFIC AIMS 
 
The protocol objectives are to compare the time for and quality of recovery, both subjective 
and objective (muscle strength), after reversal of NMB comparing 2 different reversal agents 
(SUG versus NEO) in patients undergoing moderate length surgical procedures requiring 
paralysis. 
Primary Objective 
 
To compare the difference in duration from administration of NMB reversal agent to the time 
the patient is ready for discharge from PACU after NMB reversal with sugammadex versus 
neostigmine. 
Secondary Objectives 
 
1) To compare the patient-reported quality of post operative recovery using standard 
symptoms of subclinical weakness or paralysis after NMB reversal with SUG vs NEO, 
specifically: 
a. difficulty with breathing 
b. presence of diplopia or other visual disturbances 
c. difficulty with speaking 
d. difficulty with swallowing 
e. the presence of nausea or vomiting 
f. 
the presence of pain 
g. feeling worried or anxious 
h. presence of muscle strength at the biceps brachii muscle (Oxford Scale, Appendix 1) 
 
2) To compare the differences in PACU costs associated with use of each drug 
 
3.0 
BACKGROUND AND RATIONALE 
 
Neuromuscular transmission is the transfer of a chemical impulse between a nerve and a 
muscle at the neuromuscular junction, causing muscle contraction. Transmission occurs 
when an action potential reaches the presynaptic terminal and opens calcium channels 
allowing calcium ions to enter the neuron. The release of the neurotransmitter acetylcholine 
(ACh) diffuses across the synaptic cleft and binds to the nicotinic receptors on the muscle 
fiber causing muscle contraction. 
 
Non-depolarizing neuromuscular blocking agents (NMBA) work at the neuromuscular  
junction by binding to the acetylcholine (ACh) receptor and acting as competitive antagonists, 
preventing Ach from generating an action potential, causing reversible paralysis of skeletal 
muscle. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 17-207 A(7) 
Approval date: 17-Jul-2019 
Page 9 of 27 
 
 
 
 
Neuromuscular blockade (NMB) is used by anesthesia providers in the operating room (OR) 
to facilitate endotracheal intubation and mechanical ventilation and to provide improved 
surgical conditions.1  The level of blockade is routinely measured by stimulating a peripheral 
motor nerve and evaluating the muscle response to a supramaximal stimulus (20-25% above 
that required for a maximal response). 
After administration of a neuromuscular blocking agent, the muscle response decreases in 
parallel with the number of fibers blocked, corresponding to the degree of blockade. There 
are several patterns used to evaluate neuromuscular function. We will be using the train-of- 
four (TOF) count where four supramaximal stimuli are given every 0.5 seconds.2-4 The 
muscle contracts with each stimulus and the “fade” is assessed either visually or tactilely. 
Prior to administration of a NMB agent, all four twitches are the same (control) without fade. 
 
Recovery from NMB begins with the return of the fourth twitch. Trials of NMB reversal have 
led to the general agreement that the quantitative assessment of a TOF ratio of 0.9 at the 
end of surgery should be the goal5,6. Clinically this correlates with no perceived fade, 
indicating sufficient neuromuscular recovery.7-17 
 
Residual weakness from incomplete metabolism or inadequate reversal with a 
neuromuscular blockade antagonist occurs frequently in the postoperative period18-22  adding 
increased morbidity to recovery23  and delaying discharge from the PACU and increasing 
costs.21,24 
 
Presently in our ORs we use the acetylcholinesterase inhibitor neostigmine (NEO) to reverse 
NMB. Cholinesterase inhibition increases availability of acetylcholine in the postsynaptic 
cleft. Neostigmine binds to cholinesterase and blocks enzymatic cleavage of Ach. This 
increase in Ach concentration leads not only to activation of nicotinic but also to stimulation 
of muscarinic receptors. Consequently, neostigmine is usually administered with an 
anticholinergic such as glycopyrrolate or atropine to counteract the muscarinic side effects. 
These include nausea and vomiting, bradycardia, bronchospasm and miosis. Of interest, 
high dose neostigmine or administration after the TOF ratio returns to 0.9 may increase the 
incidence of pulmonary complications and increase PACU length of stay.19,25-29 
 
Recently available on formulary at MSK is the gamma-cyclodextrin NMB reversal agent 
sugammadex, which inactivates non depolarizing aminosteroid based NMB agents by 
forming tight complexes in the vascular system and releasing the Ach receptors, reversing 
relaxation.30  Due to its direct mechanism on the NMB agent, there is no effect on the nicotinic 
or muscarinic receptors and therefore no cholinergic side effects, allowing reversal of deeper 
levels of neuromuscular blockade. 31  Several studies have shown that sugammadex more 
rapidly reverses rocuronium block than neostigmine.31-33  In addition, sugammadex has been 
shown not to impair upper airway muscle activity.34 
 
We propose to evaluate the patient’s objective and subjective post operative recovery from 
neuromuscular blockade in the PACU following reversal from rocuronium paralysis with 
either sugammadex or neostigmine in a randomized assessor and patient blinded fashion 
and to assess the impact on PACU length of stay and medication costs. Our goal is to 

Memorial Sloan Kettering Cancer Center 
IRB Number: 17-207 A(7) 
Approval date: 17-Jul-2019 
Page 10 of 27 
 
 
 
 
determine whether SUG results in improved patient safety and comfort with NMB reversal 
post operatively, and decreases the time it takes for the patient to be ready to discharge from 
the PACU. The trial will be performed in a single center major cancer center. The effects of 
SUG vs NEO have not been studied in this patient population before in the current literature. 
 
4.1 
OVERVIEW OF STUDY DESIGN/INTERVENTION 
 
4.2 
Design 
 
This will be a prospective, randomized, assessor and patient blinded study. Patients eligible 
for the trial will be those scheduled for surgical procedures expected to last ≤ 6 hours which 
require muscular paralysis. There will be a total of 101 cases needed in each arm. We  
expect to be able to complete the trial within 1-2 years. Eligible patients will be consented 
and registered for the trial during a pre-operative clinic appointment. Patients will be 
randomized to either the SUG group or the NEO group. Randomization will occur through the 
Clinical Research Database (CRDB) per institutional protocol. The process will be accessible 
only for un-blinded team members, ie those members taking care of the patient in the OR. 
The patients will also be blinded to which group they are in. 
 
In the operating room general anesthesia will be induced and maintained in a standard 
fashion. The NMB agent used for this trial will be rocuronium, an aminosteroid type of non 
depolarizing NMB. At the conclusion of surgery, the patient will be reversed with either SUG 
or NEO/GLYCO, and the time from reversal to extubation criteria are met will be documented 
along with time to extubation. 
 
The patient will then be transferred to the PACU where s/he will be evaluated by a trained 
clinician assessor blinded to the reversal agent at 30, 60 and 120 minutes (+/- 5 minutes and 
until the patient is ready for PACU discharge) after admission for quality of post operative 
recovery including: 
 
a. difficulty with breathing 
b. presence of diplopia or other visual disturbances 
c. difficulty with speaking 
d. difficulty with swallowing 
e. the presence of nausea or vomiting 
f. 
the presence of pain 
g. feeling worried or anxious 
h. presence of muscle strength at the biceps brachii muscle (Oxford Scale, Appendix 1) 
i. 
readiness for discharge from PACU (time patient meets PACU discharge criteria 
(Appendix 1) 
At discharge from PACU, the cost of the study drugs will be compared along with the time of 
the PACU stay from admission to ready to discharge (RTD). 

Memorial Sloan Kettering Cancer Center 
IRB Number: 17-207 A(7) 
Approval date: 17-Jul-2019 
Page 11 of 27 
 
 
 
 
 
 
4.3 
Intervention 
 
The goal of this study is to compare objective and subjective post operative recovery from 
rocuronium neuromuscular blockade with sugammadex (SUG) to that with neostigmine 
(NEO/GLYCO). 
 
Patients will be consented in either the pre anesthesia or surgical clinics and randomized by 
the CRDB prior to surgery to receive reversal of NMB with either SUG or NEO/GLYCO at the 
conclusion of the surgical procedure. The patient and assessors will be blinded as to the 
randomization assignment. 
 
On the day of surgery, the patient will be brought to the OR and secured onto the operative 
table after appropriate identification. Routine monitors will be placed (EKG, NIBP, SpO2, 
NMT [SunStim™ Peripheral Nerve Stimulator by SunMed]). The TOF count pattern of 
stimulation will be used, where four supramaximal stimuli are generated at 0.5 second 
intervals, to quantify the muscle response. The TOF count (number of detected muscle 
responses) will be used to guide subsequent ROC administration for maintenance of 
neuromuscular blockade. 
 
The NMT electrodes will be placed on the wrist along the ulnar nerve 5 cm apart. Since 
different muscle groups have different sensitivities to NMB35  we will use this location only for 
assessment of depth of blockade prior to reversal agent administration. As the ulnar nerve is 
more sensitive than the diaphragm to NMB, this will provide a margin of safety at reversal 
since there will be less residual neuroblockade at the diaphragm. The distal electrode will be 
placed 1 cm proximal to the flexion crease on the volar side of the wrist. The proximal 
electrode will be placed 5 cm proximal.36 For robotic and laparoscopic cases, facial nerve 
TOF will be used for intraoperative monitoring of depth of blockade as the arms will be  
tucked for these procedures. This will be done exclusively for purposes of intraoperative re- 
dosing of neuromuscular blocker. Ulnar nerve TOF will be assessed and documented prior to 
reversal administration in all cases. 
 
An intravenous catheter will be placed if not already present and a crystalloid solution will be 
started. Antibiotics, heparin and other medications will be administered as ordered by the 
surgical service. If an epidural is present, it will be used at the standard post operative 
analgesic rate. 
 
Anesthesia will be induced in a standard fashion. Prior to paralysis, a baseline twitch 
response will be elicited (TOF count 4/4 with no perceived fade). Then neuromuscular 
blockade will be achieved with rocuronium 0.6mg/kg. A Time Out will be performed and the 
patient will be positioned, prepared and draped for surgery. 
 
Anesthesia will be maintained in accordance with the current standard management 
technique. Patients on an ERAS protocol will continue on pathway. Anti-emetic medication 
will be given per institutional protocol unless contraindicated. The TOFcount will be  
measured at 15 minute intervals  and will be recorded in the anesthetic record. After recovery 

Memorial Sloan Kettering Cancer Center 
IRB Number: 17-207 A(7) 
Approval date: 17-Jul-2019 
Page 12 of 27 
 
 
 
 
from the induction dose, additional doses of ROC (0.1-0.2 mg/kg) will be administered when 
the TOF count reaches 3 to maintain the TOF count at 1-2 twitches throughout the surgical 
procedure. In the event that deeper paralysis is required for surgical exposure, we will delay 
reversal until at least one twitch has returned. It should be possible to bring the patient back 
to one twitch during surgical closure and before reversal. Acetaminophen and ketorolac will 
be used at the discretion of the attending surgeon. 
 
Ketamine, if used, will be discontinued at the beginning of surgical closure to prevent 
interference with emergence. At the conclusion of the operation, NMB will be reversed after 
fascial closure and when the patient has at least TOF count 1-2/4 at the ulnar nerve. The 
anesthesia provider will reverse the patient with either sugammadex (2 mg/kg) or  
neostigmine (0.05mg/kg up to 5mg) and glycopyrrolate (0.2mg [1ml] for each ml of 
neostigmine used), after which the patient will be emerged from anesthesia. The reversal 
agent will be listed as IRB Protocol 17-207 Study Drug A (NEO/GLYCO) or  B (SUG),  in the 
anesthesia record to maintain blinding to those other than the intraoperative anesthesia care 
team. At the time of reversal agent administration, the TOF count and fade assessment will 
be performed every minute until TOF count 4/4 with no perceived fade is achieved. When the 
patient has recovered to a TOF count 4/4 (with no perceived fade), the patient will be 
extubated. The time from administration of reversal agent (fascial closure) to TOF count 4/4 
with no perceived fade, as well as extubation will be recorded. The patient will then be 
transferred to the postoperative bed and taken to the PACU. If the TOF count does not reach 
4/4 with no perceived fade after a reasonable time (approximately 30 minutes after reversal), 
the patient may be extubated and transferred to the PACU at the discretion of the anesthesia 
provider after traditional extubation criteria have been met (Appendix 1). 
 
Upon arrival to the PACU, the patient will be admitted and vital signs recorded. The patient 
will be evaluated by a clinician, trained by the PI, who will act as a blinded assessor at 30, 
60, and 120 minutes following arrival (+/- 5 minutes until the patient meets discharge criteria) 
for the following. S/he may be assisted by a trained PACU RN or APP if necessary. The 
parameters being assessed are: 
 
a. difficulty with breathing (yes/no) 
b. presence of diplopia or other visual disturbances (yes/no) 
c. difficulty with speaking (yes/no) 
d. difficulty with swallowing (yes/no) 
e. the presence of nausea or vomiting (yes/no) 
f. 
the presence of pain (yes/no) 
g. feeling worried or anxious (yes/no) 
h. presence of muscle strength at the biceps brachii muscle (Oxford Scale, Appendix 1) 
 
At discharge from PACU, the cost of the study drugs will be compared along with the time of 
the PACU stay from admission to ready to discharge from PACU (RTD). 
 
 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS 

Memorial Sloan Kettering Cancer Center 
IRB Number: 17-207 A(7) 
Approval date: 17-Jul-2019 
Page 13 of 27 
 
 
 
 
There will be no new therapeutic or diagnostic agents used as part of this study. All drugs 
and materials will be obtained through the standard source of supply at MSKCC. The 
reversal agents used for this study, sugammadex and neostigmine/glycopyrrolate, are 
routinely stocked in the Omnicell machines in the operating rooms and are directly available 
to the anesthesia provider to dispense per the randomization. The medication will be listed 
on the anesthesia record as IRB protocol 17-207 Study Drug A (NEO/GLYCO) or  B (SUG), 
and therefore will be blinded to everyone but the intraoperative anesthesia care team. 
 
 
6.1 
CRITERIA FOR SUBJECT ELIGIBILITY 
 
6.2 
Subject Inclusion Criteria 
 
1) Adult patients age 18 years of age or greater who are capable of giving consent 
2) Undergoing surgical procedures of expected length ≤ 8 hours requiring NMB 
 
6.3 
Subject Exclusion Criteria 
 
1) Pregnancy 
2) History of documented anaphylaxis or contraindication to any of the study medications 
3) Active coronary disease with a positive cardiac stress test 
4) History of severe chronic obstructive pulmonary disease (COPD) defined as an FEV1 < 
50% of predicted 
5) Serum Creatinine ≥ 2.0 mg/dL 
6) Severe hepatic dysfunction accompanied by coagulopathy 
Definiton: 
 
• 
Known liver diease AND 
• 
INR >1.5 (except for patients on anticoagulants) AND 
• 
Platelet count <100,000/µL without other obvious cause 
7) Chronic sustained-release opioid use for > 2 weeks duration pre op (in the 30 days prior 
to surgery) 
8) Use of toremifene 
9) Significant cognitive impairment or documented psychologic impairment 
10) Myasthenia gravis or other neuromuscular disease 
11) Patients who are not eligible for standard anesthetic induction, eg, those needing rapid 
sequence induction or awake fiberoptic bronchial intubation. 
12) American Society of Anesthesiologists (ASA) Status > 3 
 
 
 
7.0 
RECRUITMENT PLAN 
 
Potential research subjects will be identified by a member of the patient’s treatment team, the 
protocol investigator, or research team at MSKCC. If the investigator is a member of the 

Memorial Sloan Kettering Cancer Center 
IRB Number: 17-207 A(7) 
Approval date: 17-Jul-2019 
Page 14 of 27 
 
 
 
 
treatment team, s/he will screen their patient’s medical records for suitable research study 
participants and discuss the study and their potential for enrolling in the research study. 
 
The principal investigator may screen the medical records of patients with whom they do not 
have a treatment relationship for the limited purpose of identifying patients who would be 
eligible to enroll in the study and to record appropriate contact information in order to 
approach these patients regarding the possibility of enrolling in the study. 
 
All patients scheduled to undergo surgical procedures booked for ≤ 6 hours who meet 
eligibility criteria will be approached for participation in the study during the surgical or 
anesthesia preoperative visit by a member of the research team. Patients using hormonal 
contraceptive therapy will be cautioned to use another method of birth control for 7 days 
postoperatively. 
The eligibility and exclusion criteria do not discriminate either explicitly or implicitly against 
gender, race or ethnicity. Consent will be obtained by the attending surgeon. Details 
pertinent to the trial, expected outcomes and potential risks and adverse outcomes will be 
discussed in detail before enrollment. Informed consent will be obtained and documented in 
the patient’s chart. The patients will then be registered and assigned a unique identification 
number. Study subjects will not receive any compensation for participation in the study. 
There will not be any additional costs for the patients derived from participation. 
 
During the initial conversation between the investigator/research staff and the patients, the 
patient may be asked to provide certain health information that is necessary to the 
recruitment and enrollment process. The investigator/research staff may also review portions 
of their medical records at MSKCC in order to further assess eligibility. They will use the 
information provided by the patient and/or medical record to confirm that the patient is  
eligible and to contact the patient regarding study enrollment. If that patient turns out to be 
ineligible for the research study, the research staff will destroy all information collected on the 
patient during the initial conversation and medical records review, except for any information 
that must be maintained for screening log purposes. 
In most cases, the initial contact with the prospective subject will be conducted either by the 
treatment team, investigator or the research staff working in consultation with the treatment 
team. The recruitment process outlined presents no more than minimal risk to the privacy of 
the patients who are screened and minimal PHI will be maintained as part of a screening log. 
For these reasons, we seek a (partial) limited waiver of authorization for the purposes of (1) 
reviewing medical records to identify potential research subjects and obtain information 
relevant to the enrollment process; (2) conversing with patients regarding possible 
enrollment; (3) handling of PHI contained within those records and provided by the potential 
subjects; and (4) maintaining information in a screening log of patients approached (if 
applicable). 
 
 
8.1 
PRETREATMENT EVALUATION 

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Page 15 of 27 
 
 
 
 
All patients will be evaluated by an attending surgeon from the appropriate service. Once 
eligibility is assessed, the patient will be approached regarding participation in the trial. Prior 
to the operation, the following will be performed (all standard before any operation). 
 
• 
The patient will sign informed consent for the surgery 
• 
The patient will have a complete history and physical examination within 4 weeks of 
surgery 
• 
Patient demographics will be recorded 
• 
Preoperative testing, which may include a basic metabolic panel, complete blood 
count, and coagulation profile per surgical service guidelines will be performed within 
4 weeks of surgery 
• 
Electrocardiogram and chest xray will be obtained if required per institutional 
guidelines 
• 
Formal medical evaluation for preoperative clearance will be obtained for any patient 
whose history warrants 
• 
For women between the ages of 11 and 50, a negative serum pregnancy test within 
30 days prior to surgery or a negative urine pregnancy test on the morning of surgery 
will be required, as per MSKCC guidelines 
 
 
9.1 
TREATMENT/INTERVENTION PLAN 
 
Patients participating in this trial will undergo routine anesthetic and perioperative care. None of the 
interventions are outside the scope of standard perioperative care. 
• 
An intravenous catheter will be placed. 
• 
An arterial line will be placed if deemed necessary. 
• 
Continuous monitoring of heart rate, blood pressure, ECG (leads II, V5), end tidal 
CO2 (etCO2), oxygen saturation (SpO2), depth of neuromuscular blockade, 
temperature, urine output and blood loss will be recorded. 
• 
The anesthetic will proceed according to current standard management using 
rocuronium as the paralytic agent. 
• 
NMB will be maintained at a TOF count of 1-2 twitches after recovery from the 
induction dose. 
• 
Intraoperative  labs will be drawn as deemed necessary by the anesthesia provider. 
• 
If the intraoperative trigger for blood products is reached (7mg/dl), or the attending 
surgeon or anesthesia provider deems it necessary, appropriate blood products will 
be transfused. 
• 
At the conclusion of fascial closure, NMB will be reversed with the trial drug, 
sugammadex (2 mg/kg) or neostigmine (0.05mg/kg up to 5mg) and glycopyrrolate 
(0.2mg [1ml] for each ml of neostigmine used) both of which are approved reversal 
agents on the MSKCC formulary. The drugs will be labeled in the anesthetic record at 
IRB Protocol 17-207 Study Drug A (NEO/GLYCO) or B (SUG). 
• 
The patient will be emerged and extubated when TOF count reaches 4/4 with no 
perceived fade and traditional extubation criteria are met. 

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• 
If the patient has not reached extubation criteria by 30 minutes after administration of 
study drug, s/he may be transported to the PACU with the ETT in place and timing of 
extubation will be documented in PACU. 
• 
Additional dosing of reversal agents will not be allowed. 
• 
At 30 minutes (+/-5) after arrival to the PACU, after routine vital signs are assessed, 
the patient will be questioned and examined by a trained clinician who is blinded to 
the study drug for the quality of post operative recovery as described above. A PACU 
RN or APP, blinded to randomization and also trained by the PI, may assist in the 
assessments. 
• 
The same parameters will be assessed at 60 and 120 minutes (+/- 5) after admission 
to the PACU then RTD will be assessed every 30 minutes until the patient meets 
eligibility  criteria. 
• 
Time to RTD from PACU will be documented (Primary Outcome) and PACU costs will 
be calculated. 
• 
The subjective parameters will be scored out of 7 and muscle strength will be 
recorded. 
 
The trial period is concluded in the PACU when the patient meets PACU discharge criteria. 
 
10.1 EVALUATION DURING TREATMENT/INTERVENTION 
 
Preoperative data 
• 
Name 
• 
Medical record number 
• 
Case number 
• 
Date of birth 
• 
Weight 
• 
Height 
• 
Laboratory values (basic metabolic panel, CBC, coags if requested by surgeon) 
• 
Medications 
Intraoperative  data 
• 
Standard intraoperative monitoring will be carried out for all patients 
• 
Volume and types of fluids given intraoperatively 
• 
Estimated blood loss and urine output 
• 
Total dose of rocuronium used and time of last dose 
• 
Time of surgical fascial closure 
• 
Intraoperative  complications, if any 
• 
Depth of NMB (TOF count) at the time of reversal agent administration 
• 
Time and quality of NMB reversal (TOF count, presence of fade) 
• 
Time extubation criteria are met (See appendix 1) 

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• 
Time of extubation whether or not TOF count 4/4 with no perceived fade is metTime 
patient leaves OR (or is deemed ready to leave OR by intraoperative anesthesia care 
team in the event of PACU hold) 
• 
Time of arrival to PACU 
 
At 30, 60 and 120 minutes (+/-5) after arrival to the PACU, the patient will be assessed for 
symptoms and complications relevant to this patient population.   In addition to the below, patients 
will be assessed for the presence of any adverse events per MSKCC standard PACU care. In the 
PACU, the patient is covered by nursing at a ratio of 1:1 or 1:2 with continuous bedside evaluation of vital 
signs, hemodynamics and telemetry in a critical care setting. Patients are assessed as per nursing protocol and 
any adverse events that come up are addressed and documented by the nurse and the APP, possibly the 
attending and a CIS event note is written. This is the standard of MSK post operative care and documentation 
in the PACU. We will review these records for inclusion  in our adverse events reporting. 
 
Patients will be asked to report: 
 
a. difficulty with breathing (yes/no) 
b. presence of diplopia or other visual disturbances (yes/no) 
c. difficulty with speaking (yes/no) 
d. difficulty with swallowing  (yes/no) 
e. the presence of nausea or vomiting  (yes/no) 
f. 
the presence of pain (yes/no) 
g. feeling worried or anxious (yes/no) 
h. presence of muscle strength at the biceps brachii muscle (Oxford Scale, 
Appendix 1) 
 
Except for the evaluation of muscle strength, the assessments will be made in a binary fashion. 
 
• 
Time PACU discharge criteria (Appendix 1) are met 
At discharge from PACU 
• 
Cost of PACU stay from admission to Ready to Discharge 
 
 
 
11.0 
TOXICITIES/SIDE EFFECTS 
 
The potential toxicities/side effects of this study pertain to those potentially and specifically 
associated with each operative procedure. Side effects from each of the study drugs are 
infrequent and may include bradycardia, nausea, anaphylaxis  and hypersensitivity. Patients 
will be assessed in PACU for any adverse events and documented as described above. 
 
All complications will be prospectively recorded and any complication felt to be due to the 
reversal medication will be reported to the IRB within 5 days. An anesthesia research study 
assistant will query the Memorial Sloan-Kettering Surgical Secondary Events Program 
Database at 30 days post-operatively for any potential morbidity data for patients enrolled in 

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Page 18 of 27 
 
 
 
 
the study. We do not expect any adverse events or side effects from the study medications 
that are not evident immediately after administration. 
 
 
12.1 CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT 
 
The primary objective of this study is to determine whether SUG, as compared to NEO 
decreases time for patients to be ready for discharge from the PACU and associated cost 
savings as well as quality of patient recovery from NMB. 
 
Secondary patient-reported parameters being evaluated are: 
 
a. difficulty with breathing 
b. presence of diplopia or other visual disturbances 
c. difficulty with speaking 
d. difficulty with swallowing 
e. the presence of nausea or vomiting 
f. 
the presence of pain 
g. feeling worried or anxious 
h. presence of muscle strength at the biceps brachii muscle (Oxford Scale, 
Appendix 1) 
• 
Time patient meets PACU discharge criteria (Appendix 1) 
 
All questions except the Oxford Scale muscle strength assessment will be answered in a 
binary yes/no fashion. 
 
These parameters will be evaluated in the PACU at 30, 60 and 120 minutes (+/- 5) after 
arrival. RTD from PACU will be assessed at 30 minute intervals until criteria are reached. 
At discharge from PACU, the cost of the PACU stay from admission to ready to discharge 
will be calculated including the cost of the study medication when unblinding occurs. 
We do not anticipate any obstacles to assessing patient response or inclusion in the study 
results. 
 
 
13.0 
CRITERIAFOR REMOVAL FROM STUDY 
 
A subject may be removed from the study at any time if the attending surgeon or  anesthesia 
provider deems it necessary for patient safety, or if the patient expresses desire to be removed. We 
do not expect any toxicity associated with the study intervention. 
 
 
14.0 
BIOSTATISTICS 

Memorial Sloan Kettering Cancer Center 
IRB Number: 17-207 A(7) 
Approval date: 17-Jul-2019 
Page 19 of 27 
 
 
 
 
This is a randomized assessor blinded study comparing two reversal agents: neostigmine (NEO, 
control arm) and sugammadex (SUG, intervention arm) in terms of time for and quality of recovery 
after reversal of NMB. We plan to enroll 202 patients (101 in each treatment arm) with planned 
moderate length surgical procedures requiring paralysis. The primary outcome is the duration 
between administration of NMB reversal agent and the time the patient is ready for discharge from 
PACU (PACU discharge criteria, Appendix  1). 
 
The sample size calculation is first based on a hypothesized ratio of 0.80 in SUG to NEO mean 
duration (i.e., the mean duration between NMB reversal agent and ready for PACU discharge under 
SUG  is 20% shorter than the mean duration under NEO). This hypothesis based on the ratio of 
means can then be translated into a hypothesis about the difference in mean duration on the log 
scale for the purpose of sample size calculation and interim and final analyses. This approach was 
used because there is no published literature with the necessary statistics in this particular 
population of interest. 
 
Stating the hypothesis as a ratio requires specification of (1) the hypothesized ratio and (2) the 
coefficient of variation (CV = standard deviation divided by mean) to describe the amount of 
variability relative to the mean. The hypothesized ratio of 0.80 in SUG to NEO mean duration is 
within the range of estimated reduction in other populations37,38. Literature also report CV between 
0.2 and 0.4 in the outcome measures among other populations, so we proceed with a more 
conservative choice of CV of 0.5 for this study. Hence, the hypothesis based on the ratio of 0.8 and 
CV of 0.5 is equivalent to a two-sample t-test assuming logged-mean of 0 under NEO versus -0.223 
under SUG, with the standard deviation of 0.472. 
Based on the two-sample t-test of two means on log scale and two-sided alpha of 0.05, a total 
sample size of 192 patients who undergo surgery yields 90% power to detect the desired differences 
in logged-means, or equivalently, a ratio of 0.8 in SUG to NEO mean duration. This sample size also 
allows for an interim analysis halfway through enrollment, using O’Brien-Fleming boundaries with 
Lan de Mets spending function for both efficacy and futility. If p≤0.002 at the interim analysis, 
enrollment will stop with the conclusion that PACU stay is significantly different between the 
treatments. If 0.002<p<0.846, the trial will continue to full enrollment, and we will conclude that the 
treatments are significantly different if p<0.049. We increase the sample size by 5% (total 202 
patients) to address drop outs or missing primary outcomes due to any reason (e.g., surgery did not 
occur). Evaluable patients are those randomized, completed surgery, and are able to provide the 
primary outcome of duration between administration of NMB reversal agent and ready to discharge 
from PACU. 
Analysis of the primary outcome will utilize the two-sample t-test to compare the two randomized 
treatment arms in terms of the mean duration between reversal of NMB to ready for PACU 
discharge on the log scale. The conclusion will also be presented in terms of the ratio. The primary 
analysis will be performed under the intent-to-treat (ITT) principle, including all randomized patients 
in the evaluable set. The analysis of the primary outcome will be repeated with modified ITT to 
exclude patients with intraoperative/PACU complications (e.g., unable to extubate). 
 
In reviewing institutional data, the average number of patients who die in the PACU is 1 every 5+ 
years, and return to OR from PACU is approximately 1 every year. In the rare case that patients 

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Page 20 of 27 
 
 
 
 
could only contribute only partial information on the primary endpoint, we may pursue survival 
analysis approach instead, comparing the duration until ready to PACU discharge, and censored at 
time of PACU exit other than meeting discharge criteria, taking into account potential informative 
censoring. Accrual rate is 8-16 per month, and the study is expected to be completed in 
approximately one to two years. 
Secondary outcomes related to the quality of post-operative recovery during PACU stay will be 
measured at 30, 60 and 120 minutes (+/-5) after arrival to the PACU. Secondary patient-reported 
outcomes will be analyzed using the mixed-effects models with random effects (patient-level) and 
fixed effects (time point of measurement and arm assignment). Outcomes measured on a 
continuous scale will be analyzed with the identity link in the longitudinal models, while binary 
outcomes will be analyzed with logit link: Oxford scale of muscle strength at the biceps brachii 
muscle (0-5 likert scale, Appendix 1); quality of life measures relevant to the current study will be 
summarized analyzed separately, such as difficulty with breathing, presence of pain, and feeling 
worried or anxious (yes/no for occurrence of each item, Appendix 1). These analyses are  
exploratory because they are of secondary interest and we do not estimate statistical power. The 
age of patients in the oncological surgical category may be higher than general anesthesia cases as 
a whole. Age affects pharmacokinetics and pharmacodynamics and hence may bias the treatment 
effect (Br J Anaesth 2011 PMID 21531745). As an exploratory objective, we will perform subgroup 
analyses of the primary and secondary objectives only among the elderly patients (>70 years old).39 
As such, randomization of patients will be stratified by age (<70 years vs ≥ 70 years). 
 
Costs associated with the use of each drug and relationship to the duration of PACU stay will be 
compared between the two treatment arms. Costs of drugs and PACU stay (from arrival to ready for 
discharge) will be obtained from pharmacy and administration. As of June 19, 2016, the cost of each 
reversal medication is $80 for NEO ($50 NEO and $30 Glyco prefilled syringes) and $90 for SUG 
200mg. Cost of PACU stay from admission to ready for discharged will be estimated based on the 
15-minute PACU costs quoted by administration (includes surgeon and anesthesia provider’s 
reimbursement, facility fees etc.). The net cost of SUG (and NEO) is calculated as the drug’s 
acquisition cost minus the value of any reduction in PACU recovery with the drug. Cost analyses will 
be conducted based on pairwise threshold analyses, which addresses the question “how much 
reduction in recovery time would SUG need to achieve, and with what value per minute of staff time, 
to justify its additional acquisition price?” 40 
The rate of removal will be reported with the study results. Patients who are removed from the study 
intraoperatively will be continued to be followed unless consent is withdrawn. Pulmonary and airway 
complications in the PACU will be summarized by arms. Any complications which occur will be 
documented and submitted as potential SAEs as outlined in Section 17.2. 
 
The evaluable criterion also includes the type of recording device used intraoperatively: randomized 
patients who are on any recording device other than the SunStim monitors will be considered 
inevaluable (and excluded from anlyses) due to non-reproducible/unreliable  recordings. These 
patients will be replaced in the study. 

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15.1 
RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION PROCEDURES 
 
15.2 
Research Participant Registration 
 
 
Confirm eligibility  as defined in the section entitled  Inclusion/Exclusion  Criteria. Obtain 
informed consent, by following  procedures  defined in section entitled  Informed  Consent 
Procedures. During the registration  process registering  individuals  will be required to 
complete a protocol specific Eligibility  Checklist. The individual  signing the Eligibility 
Checklist is confirming whether or not the participant  is eligible  to enroll in the study. 
Study staff are responsible  for ensuring that all institutional  requirements  necessary to 
enroll a participant  to the study have been completed. See related Clinical Research 
Policy and Procedure #401 (Protocol Participant  Registration). 
 
 
15.3 
Randomization 
 
This is an assessor and patient only blinded randomized trial comparing sugammadex  
versus neostigmine. There will be a total of 202 patients recruited for this study, 101 in each 
arm, consented during a preoperative clinic appointment. Randomization will be stratified by 
age (<70 years vs ≥ 70 years). After eligibility is established and consent is obtained, patients 
will be registered by the CRCs in the Clinical Trials Management System (CTMS) and 
randomized using the Clinical Research Database (CRDB). Only the anesthesia research 
team (CRMs and CRCs) and the anesthesia care team in the OR will have access to the 
unblinded treatment assignments. 
16.1 
DATA MANAGEMENT ISSUES 
 
A clinical research coordinator (CRC) will be assigned to the study. The responsibilities of the 
CRCinclude project compliance, patient registration, assistance with data collection, 
abstraction and entry, data reporting, regulatory monitoring, problem resolution and 
prioritization and coordination of the activities of the protocol study team. The CRC will be 
integrated into current weekly and monthly meetings where complications are recorded, 
procedures reviewed and outcomes documented. The PI’s will personally meet with the CRC 
on a weekly basis to assist with and review the collection and entry of data. 
 
All data to be collected are listed within Section 10.0, and will only be used for the purposes 
of the study. It will be maintained in a confidential clinical research database by research 
study personnel only under the direct supervision of the principal investigator. The database 
will be kept in a password protected computer and will not be transferred outside the hospital 
network. A minimum dataset will be kept in CRDB. The data will be linked to the patients by 
means of unique tracking subject numbers, the key to which will also be password protected 
and only to be accessed by research personnel. Data will be reported to the IRB as required. 
We estimate accrual to be approximately 2-4 patients per week allowing completion and 
reporting of the study within 1-2 years. 

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16.2 
Quality Assurance 
 
Weekly registration reports will be generated to monitor patient accruals and completeness 
of registration data. Routine data quality reports will be generated to assess missing data 
and inconsistencies. Accrual rates and extent and accuracy of evaluations and follow up will 
be monitored periodically throughout the study period and potential problems will be brought 
to the attention of the study team for discussion and action. 
 
Random sample data quality and protocol compliance audits will be conducted by the study 
team at a minimum of two times per year, more frequently if indicated. 
 
The principal investigator will maintain final responsibility for the maintenance, quality and 
integrity of all data collection during the study and during the final analysis of data. Breaches 
of protocol, problems with eligibility,  informed consent or discrepancies in data accuracy will 
be reported to the IRB at MSKCC as required. 
16.3 
Data and Safety Monitoring 
 
The Data and Safety Monitoring (DSM) Plans at Memorial Sloan-Kettering Cancer Center 
were approved by the National Cancer Institute in September 2001. The plans address the 
new policies set forth by the NCI in the Document entitled ”Policy of the National Cancer 
Institute for Data and Safety Monitoring of Clinical Trials,” which can be found at:  
http://cancer.gov/clinicaltrials/conducting/dsm -guidelines. The DSM Plans at MSKCC were 
established and are monitored by the Office of Clinical Research. The MSKCC Data and 
Safety Monitoring Plans can be found on the MSKCC Intranet at:  
http:/mskweb5.mskcc.org/intranet/assets/tables/content/359709/DSMPlans07.pdf. 
 
There are several different mechanisms by which clinical trials are monitored for data, safety 
and quality. There are institutional processes in place for quality assurance (e.g. protocol 
monitoring, compliance and data verification audits, therapeutic response, and staff 
education on clinical research QA) and departmental procedures for quality control. In 
addition, there are two institutional committees that are responsible for monitoring the 
activities of our clinical trials programs. The committees: Data and Safety Monitoring 
Committee (DSMC) for Phase I and II clinical trials, and the Data and Safety Monitoring 
Board (DSMB) for Phase III clinical trials, report to the Center’s Research Council and 
Institutional Review Board. 
 
During the protocol development and review process, each protocol will be assess ed for its 
level of risk and degree of monitoring required. Every type of protocol (e.g. NIH sponsored, in 
house sponsored, industrial sponsored, NCI cooperative group, etc.) will be addressed and 
the monitoring procedures will be established at the time of protocol activation. 
17.1 
PROTECTION OF HUMAN SUBJECTS 
 
▪ 
The responsible principal investigator (PI) will ensure that this study is conducted in 
agreement with the declaration of Helsinki (Tokyo, Venice, Hong King, Somerset 

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West and Edinburgh amendments). The study will seek to protect the rights of human 
subjects in every way. 
▪ 
The potential risks, including adverse drug reactions and potential benefits in terms of 
post operative recovery will be discussed in detail with the patients. 
▪ 
Potential side effects will also be discussed with the patients. 
▪ 
No patient will be required to participate in the study and participation, or refusal to do 
so, will not affect the patient’s care or treatment. 
▪ 
The patient will not incur any financial cost as a result of participation in the study. 
▪ 
Participation will be purely voluntary, and subjects will not be reimbursed for 
participation in the study. 
▪ 
Throughout the study, patient confidentiality will be maintained. No results of the 
study will be presented or discussed in a fashion that will allow identification of a 
particular patient in the study. 
▪ 
All adverse events will be fully disclosed to the IRB in a timely fashion as required. 
 
17.2 
Privacy 
 
The consent indicates that individualized  de identified information collected for the purposes 
of this study may be shared with other qualified researchers. Only researchers who have 
received approval from MSK will be allowed to have access to this information which will not 
include protected health information, such as the participant’s name, except for dates. It is 
also stated in the Research Authorization that their research data may be shared with other 
qualified  researchers. 
MSK’s Privacy Office may allow the use and disclosure of protected health information 
pursuant to a completed and signed Research Authorization form. The use and disclosure of 
protected health information will be limited to the individuals described in the Research 
Authorization form. A Research Authorization form must be completed by the Principal 
Investigator and approved by the IRB and Privacy Board (IRB/PB). 
17.3 
Serious Adverse Event (SAE) Reporting 
 
An adverse event is considered serious if it results in ANY of the following outcomes: 
• 
Death 
• 
A life-threatening adverse event 
• 
An adverse event that results in inpatient hospitalization or prolongation of existing 
hospitalization 
• 
A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• 
A congenital anomaly/birth defect 
• 
Important Medical Events (IME) that may not result in death, be life threatening, or 
require hospitalization may be considered serious when, based upon medical judgment, 
they may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition 

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Note: Hospital admission for a planned procedure/disease treatment is not considered an 
SAE. 
 
SAE reporting is required as soon as the participant starts investigational 
treatment/intervention. SAE reporting is required for 30-days after the participant’s last 
investigational treatment or intervention. Any events that occur after the 30-day period that is 
unexpected and at least possibly related to protocol treatment must be reported. 
 
Please note: Any SAE that occurs prior to the start of investigational treatment/intervention 
and is related to a screening test or procedure (i.e., a screening biopsy) must be reported. 
 
All SAEs must be submitted in PIMS. If an SAE requires submission to the HRPP office per 
IRB SOP RR-408 “Reporting of Serious Adverse Events’, the SAE report must be submitted 
within 5 calendar days of the event. 
 
. 
 
The report should contain the following information: 
 
• 
The date the adverse event occurred 
• 
The adverse event 
• 
The grade of the event 
• 
Relationship of the adverse event to the treatment(s) 
• 
If the AE was expected 
• 
Detailed text that includes the following 
o A explanation of how the AE was handled 
o A description of the subject’s condition 
o Indication if the subject remains on the study 
• 
If an amendment will need to be made to the protocol and/or consent form 
• 
If the SAE is an Unanticipated Problem 
 
 
17.2.1 
 
There is no additional SAE reporting information required by the drug supplier. 
 
18.1 
INFORMED CONSENT PROCEDURES 
 
Before protocol-specified procedures are carried out, consenting professionals will explain  
full details of the protocol and study procedures as well as the risks involved to participants 
prior to their inclusion in the study. Participants will also be informed that they are free to 
withdraw from the study at any time. All participants must sign an IRB/PB-approved consent 
form indicating their consent to participate. This consent form meets the requirements of the 
Code of Federal Regulations and the Institutional Review Board/Privacy Board of this Center. 
The consent form will include the following: 

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IRB Number: 17-207 A(7) 
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Page 25 of 27 
 
 
 
 
1. The nature and objectives, potential risks and benefits of the intended study. 
2. The length of study and the likely follow-up required. 
3. Alternatives to the proposed study. (This will include available standard and 
investigational therapies. In addition, patients will be offered an option of supportive 
care for therapeutic studies.) 
4. The name of the investigator(s) responsible for the protocol. 
5. The right of the participant to accept or refuse study interventions/interactions and to 
withdraw from participation at any time. 
Before any protocol-specific procedures can be carried out, the consenting professional will 
fully explain the aspects of patient privacy concerning research specific information.  In 
addition to signing the IRB Informed Consent, all patients must agree to the Research 
Authorization component of the informed consent form. 
Each participant and consenting professional will sign the consent form. The participant must 
receive a copy of the signed informed consent form. 
 
 
19.0 
REFERENCES 
 
1. 
Zhang B, Hepner DL, Tran MH, Friedman M, Korn JR, Menzin J. Neuromuscular blockade, 
reversal agent use, and operating room time: retrospective analysis of US inpatient 
surgeries. Curr Med Res Opin. 2009;25(4):943-950. 
2. 
Ali HH, Utting JE, Gray C. Stimulus frequency in the detection of neuromuscular block in 
humans. Br J Anaesth. 1970;42(11):967-978. 
3. 
Ali HH, Utting JE, Gray TC. Quantitative assessment of residual antidepolarizing block. II. Br 
J Anaesth. 1971;43(5):478-485. 
4. 
Ali HH, Utting JE, Gray TC. Quantitative assessment of residual antidepolarizing block. I. Br 
J Anaesth. 1971;43(5):473-477. 
5. 
Kopman AF, Yee PS, Neuman GG. Relationship of the train-of-four fade ratio to clinical signs 
and symptoms of residual paralysis in awake volunteers. Anesthesiology. 1997;86(4):765- 
771. 
6. 
Debaene B, Plaud B, Dilly MP, Donati F. Residual paralysis in the PACU after a single 
intubating dose of nondepolarizing muscle relaxant with an intermediate duration of action. 
Anesthesiology.  2003;98(5):1042-1048. 
7. 
Eikermann M, Groeben H, Husing J, Peters J. Predictive value of mechanomyography and 
accelerometry for pulmonary function in partially paralyzed volunteers. Acta 
anaesthesiologica  Scandinavica. 2004;48(3):365-370. 
8. 
Naguib M, Kopman AF, Ensor JE. Neuromuscular monitoring and postoperative residual 
curarisation: a meta-analysis. Br J Anaesth. 2007;98(3):302-316. 
9. 
Lien CA, Kopman AF. Current recommendations for monitoring depth of neuromuscular 
blockade. Current opinion in anaesthesiology. 2014;27(6):616-622. 
10. 
Berg H, Roed J, Viby-Mogensen  J, et al. Residual neuromuscular block is a risk factor for 
postoperative pulmonary complications. A prospective, randomised, and blinded study of 
postoperative pulmonary complications after atracurium, vecuronium and pancuronium. Acta 
anaesthesiologica  Scandinavica. 1997;41(9):1095-1103. 
11. 
Eikermann M, Groeben H, Husing J, Peters J. Accelerometry of adductor pollicis muscle 
predicts recovery of respiratory function from neuromuscular blockade. Anesthesiology. 
2003;98(6):1333-1337. 

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20.0 
APPENDICES 
 
• 
Appendix 1: Postoperative Assessment Form