Clinical trial NCT03532178
Conditions: Neuromuscular Blockade
Keywords: Electroconvulsive Therapy, Neuromuscular Blockade
Sponsor: University of California, San Francisco
Start date: 2019-01-01; Completion date: 2022-04-01
Enrollment: 44 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The investigators propose to compare the recovery of neuromuscular blockade from rocuronium reversal by sugammadex to succinylcholine in ECT.

Detailed description:
The proposed study is a single center, randomized, double-blind (patients, psychiatrists and outcome assessor), cross-over clinical trial comparing the recovery of neuromuscular blockade from rocuronium with reversal of sugammadex to succinylcholine in participants receiving ECT. The primary outcome will be the measurement of time when the first train-of-four (TOF) twitch (T1) returns to 90% of baseline. The secondary aims are to document the safety (adverse event rates) of rocuronium/sugammadex compared to succinylcholine in ECT patients. The exploratory aims are to establish the perioperative efficacy and efficiency of sugammadex reversal of rocuronium in ECT procedures in comparison with succinylcholine.

Arms: arm 1: rocuronium + sugammadex / succinylcholine + normal saline arm 2: succinylcholine + normal saline / rocuronium + sugammadex
Interventions: intervention 1: Group A. "Muscle relaxant #1": rocuronium + sugammadex; "Muscle relaxant #2": succinylcholine +saline intervention 2: Group B. "Muscle relaxant #2": succinylcholine +saline; "Muscle relaxant #1": rocuronium + sugammadex;
Intervention descriptions: intervention 1: The participants will be randomized to start with "Muscle relaxant #1" in the first study treatment, and will switch to "Muscle relaxant #2" in the second study treatment period. intervention 2: The participants will be randomized to start with "Muscle relaxant #2" in the first study treatment, and will switch to "Muscle relaxant #1" in the second study treatment period.

Protocol documents:
Prot_SAP_000.pdf: 
Protocol  
Number 17-22999 
Confidential 
Version #: 1 
Version Date: 11/03/2017 
Page 7 of 31 
Protocol Template Effective: 07 JAN 2015 
PROTOCOL SYNOPSIS 
TITLE 
A Double-Blind, Randomized, Crossover Design Study To Compare 
The Rocuronium Reversal By Sugammadex To Succinylcholine For 
Electroconvulsive Therapy (ECT)  
SPONSOR 
Chanhung Lee 
FUNDING 
ORGANIZATION 
Merck & Co, Inc. 
NUMBER OF SITES 
1 
RATIONALE 
The purpose of this study is to find out if a novel drug, sugammadex, 
can be used to reverse the muscle relaxation during the 
Electroconvulsive Therapy (ECT).  ECT exerts its therapeutic effect 
by inducing generalized seizures. To protect the patients from harmful 
seizure injury, neuromuscular blockade is used to control excessive 
muscle movement during the treatment.  Since the optimal length of 
therapeutic seizure effects is brief, fast recovery of the neuromuscular 
function after the treatment is desirable. 
Succinylcholine has been traditionally used in ECT for muscle 
relaxation because of its fast recovery after the procedure, but with 
obvious limitations and side-effects.  Rocuronium is a different 
muscle relaxant providing excellent blocking conditions and has been 
commonly used in surgery, but not in ECT because of its long 
duration of action. Sugammadex is a novel reversal drug for 
rocuronium,  which has recently been approved by the FDA. 
Sugammadex can reverse the action of rocuronium on neuromuscular 
blockade.   Researchers want to learn whether sugammadex can be 
used in combination with rocuronium to provide a timely recovery of 
neuromuscular function after the ECT treatment.  
STUDY DESIGN 
This is a randomized, double-blind, placebo-controlled phase 2 study. 
PRIMARY 
OBJECTIVE 
The primary objective is to further explore the pharmacology of 
sugammadex in electroconvulsive therapy (ECT) by measuring 
neuromuscular recovery time from sugammadex reversal of 
rocuronium, compared to traditionally used succinylcholine.   
SECONDARY 
OBJECTIVES 
Secondary aims are to document the safety and tolerability (adverse 
event rates) of rocuronium/sugammadex compared to succinylcholine 
in ECT patients, and to exploer perioperative efficacy and efficiency 
of sugammadex reversal of rocuronium in ECT procedures. 
NCT03532178


Protocol  
Number 17-22999 
Confidential 
 
Version #: 1 
Version Date: 11/03/2017 
Page 8 of 31 
Protocol Template Effective: 07 JAN 2015  
NUMBER OF 
SUBJECTS 
50 
SUBJECT 
SELECTION 
CRITERIA 
Inclusion Criteria: 
x 
Age ≥ 18 years 
x 
Eligible and scheduled for ECT 
x 
Has the capacity to consent for the study 
 
Exclusion Criteria: 
x 
Any acute major organ failure in the last 30 days 
x 
Any known or suspected neuromuscular disorders 
x 
Any history of allergic reaction or intolerance to sugammadex, 
rocuronium, or succinylcholine 
x 
Any conditions with severe renal impairment, including those 
requiring dialysis 
x 
Anyone currently taking hormonal contraceptives 
x 
Anyone taking anti-coagulants, including vitamin K 
antagonists, unfractionated heparin, low molecular weight 
heparinoids, rivaroxaban, and dabigatran 
 
TEST PRODUCT, 
DOSE, AND ROUTE 
OF 
ADMINISTRATION 
Sugammadex at 4 mg/kg, IV  
(after rocuronium is administered for ECT) 
 
CONTROL 
PRODUCT, DOSE 
AND ROUTE OF 
ADMINISTRATION 
Succinylcholine at 1 mg/kg IV  + normal saline IV   
  
DURATION OF 
SUBJECT 
PARTICIPATION 
AND DURATION OF 
STUDY 
Subjects will be on study for up to two treatments 
Screening:  up to 7 days 
Treatment:  standard procedure time ( about 2 hours) 
Follow-up:  24 hours by phone 
The total duration of the study is expected to be one month for subject 
recruitment and for final subject follow-up. 


Protocol  
Number 17-22999 
Confidential 
 
Version #: 1 
Version Date: 11/03/2017 
Page 9 of 31 
Protocol Template Effective: 07 JAN 2015  
CONCOMMITANT 
MEDICATIONS 
Allowed: 
Standard therapy for patients’ medical diseases is allowed except for 
treatments noted in the exclusion criteria described above and as noted 
in the prohibited medications section below.   
 
Prohibited: 
x 
hormonal contraceptives 
x 
anti-coagulants, including vitamin K antagonists, unfractionated 
heparin, low molecular weight heparinoids, rivaroxaban, and 
dabigatran 
 
EFFICACY 
EVALUATIONS 
 
PRIMARY ENDPOINT 
x 
Neuromuscular recovery time from sugammadex reversal of 
rocuronium, compared to traditionally used succinylcholine. 
SECONDARY 
ENDPOINTS 
x Explore perioperative efficacy and efficiency of sugammadex 
reversal of rocuronium in ECT procedures. 
OTHER 
EVALUATIONS 
 
SAFETY 
EVALUATIONS 
x Safety and tolerability (adverse event rates)  
 
PLANNED INTERIM 
ANALYSES  
An interim analysis is planned after approximately 30% of the patients 
have been enrolled and completed follow-up to assess safety and 
provide estimates of within and between patient variability in the 
recovery time of muscle relaxants.    The interim analysis for safety 
will be conducted by the study team. Serious adverse events will be 
monitored by the investigators on an ongoing basis throughout the 
study. 
STATISTICS 
Primary Analysis Plan 
This is a two-period, two-treatment, 2x2 cross-over study. Although it 
is highly likely that the washout period is adequate for eliminating the 
first order carry-over effects since all repeated procedures are 
scheduled at least 48 hours apart, which exceeds the duration for all 
the involved medications, we will exam the period and carryover 
effects using a term for time period and an interaction term between 
the treatment group and time period. Intent-to treat analyses will be 
used for primary and secondary outcomes.  For the primary outcome, 
the comparison of recovery time of T1 to 90% baseline, a continuous 
variable, between the groups of rocuronium /sugammadex and the 


Protocol  
Number 17-22999 
Confidential 
 
Version #: 1 
Version Date: 11/03/2017 
Page 10 of 31 
Protocol Template Effective: 07 JAN 2015  
succinylcholine /saline placebo, will be analyzed using the two sample 
t test.   
Rationale for Number 
of Subjects 
Based on the study by Lee, et al,8 comparing high dosage of  
rocuronium 1.2 mg/kg in combination with high dosage reversal of 
sugammadex 16mg/kg with succinylcholine 1mg/kg, the recovery 
time T1 to 90% in succinylcholine was 10.9 ± 2.4 minutes. The 
reported T1 to 90% 4mg/kg sugammadex reversed recovery counted 
from  time of rocuronium 0.6 mg/kg (the same proposed dosage as in 
our study) administration ranged from 6 to 9.3 minutes.5, 10   With our 
estimation of two-tailed α=0.05, β=0.2, the reported minimum mean 
difference of 1.6 (10.9 minus 9.3) minutes, SD of succinylcholine of 
2.4 minutes, the calculated sample size for a cross-over trial would be 
35.  
At UCSF, there are usually 60 ECT patients each year. With a 
conservative estimate of 75% consent rate, we will have at least 45 
patients to participate in the study. Even conservatively allowing a  
20% drop-off rate, we feel that our enrollment up to 50 will provide 
sufficient power for the study. 
 

ICF_001.pdf: 
[January, 2018]
PAGE 1 OF 8
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
CONSENT TO PARTICIPATE IN A RESEARCH STUDY
Study Title: A Double-Blind, Randomized, Crossover Design Study To Compare The 
Rocuronium Reversal By Sugammadex To Succinylcholine For Electroconvulsive Therapy (ECT) 
Research Project 
Director:
Chanhung Lee M.D., PhD, Professor of Anesthesia.  
UCSF, Box 1363  
e-mail: Chanhung.lee@ucsf.edu
This is a clinical research study.  Your study doctor(s), Chanhung Lee, Ronald Miller, Descartes 
Li, Tobias Marton and Ramotse Saunders, from the UCSF Departments of Anesthesia and 
Psychiatry, will explain the study to you.
Research studies include only people who choose to take part.  Please take your time to make 
your decision about participating.  You may discuss your decision with your family and friends 
and with your health care team.  If you have any questions, you may ask your study doctor.
You are being asked to take part in this study because you are scheduled for Electroconvulsive 
Therapy to treat depression and other mental disorders.
Why is this study being done?
The purpose of this study is to find out if a newer drug, sugammadex, can be used to help you to 
reverse the muscle relaxation during the Electroconvulsive Therapy (ECT).  ECT exerts its 
treatment effect by inducing generalized seizures. To protect the patients from harmful seizure 
injury, a muscle relaxation drug is used to control excessive muscle movement during the 
treatment.  Since the optimal length of treatment seizure effects is brief, fast recovery of the 
muscle function after the treatment is desirable.
Succinylcholine has been traditionally used in ECT for muscle relaxation because of its fast 
recovery after the procedure, but with obvious limitations and side-effects, including in patients 
with muscle diseases, as well as risks of increased potassium above normal levels, increased 
pressure inside the eyes, causing changes in the rhythm of heart beats.
Rocuronium is a different muscle relaxant providing excellent blocking conditions and has been 
commonly used in surgery, but not in ECT because of its long duration of action. Sugammadex 
is a novel reversal drug for rocuronium,  which has recently been approved by the FDA. 
Sugammadex can reverse the action of rocuronium on muscle relaxation.   Researchers want to 
learn whether sugammadex can be used in combination with rocuronium to provide a timely 
recovery of muscle function after the ECT treatment. 
This study is being funded, in part by Merck & Co, Inc., as well as UCSF departmental funds.  
The investigators have no financial or proprietary interests.
NCT03532178
12/10/2020


[January, 2018]
PAGE 2 OF 8
How many people will take part in this study?
 About 50 people scheduled for Electroconvulsive Therapy will take part in this study at UCSF.
What will happen if I take part in this research study?
Before you begin the main part of the study...
You will talk to your psychiatrists and anesthesiologists in the clinic and before the procedures, 
and the study will be explained to you.   
During the main part of the study...
On the day of the procedure, you will receive the normal ECT and standard care as you would 
otherwise take the treatment. There will be no change in your medical management, other than 
the study drugs for muscle relaxation and recording your recovery from it. You will be given the 
anesthesia exactly the same except the study medications for muscle relaxation and reversal. 
Each participant will be on the study for two ECT treatments. You will receive Muscle Relaxant 
#1 (the traditionally used succinylcholine +saline) for one ECT, and receive Muscle Relaxant #2 
(rocuronium + sugammadex) in the other ECT treatment period. 

The participants will be “randomized” to two groups: 
o
Group A will first receive “Muscle Relaxant #1” in one ECT, then switch to
“Muscle Relaxant #2” in the next study ECT treatment period
o
Group B will first receive “Muscle Relaxant #2” in one ECT, then switch to
“Muscle Relaxant #1” in the next study ECT treatment period

Randomization means that you are put into a group by chance.  A computer program will
place you in one of the groups.  Neither you nor your doctor can choose the group you
will be in.  You will have an equal chance of being placed in either group. The ECT
procedures will be identical, whether you are in group "A" or "B", except for the order of
the study drugs.

Double-blind means that neither the patients nor the psychiatrists or study outcome
assessors know the assignment of the treatment groups, but only the anesthesiologists
will know which medication is given to each patient.  This procedure is utilized to
prevent bias in research results.

The time from administration of the drugs to satisfactory recovery of muscle strength will
be measured in all study treatment groups.  Your ECT procedure, anesthesia medications
and devices, medical conditions, vital signs, time to meet discharge criteria in Post
Anesthesia Care Unit will be recorded as part of your normal care.


[January, 2018]
PAGE 3 OF 8

Study location: All study procedures will be done at Moffitt-Long Hospital of UCSF 
Medical Center as the same location where you normally receive your ECT treatment. 

You will receive a follow-up phone call to find out how you are doing on the next day after 
the study of your ECT procedure.
Study Plan
Another way to find out what will happen to you during the study is to read the chart below. Start 
reading at the top and read down the list, following the lines and arrows.
ECT treatments scheduled 
Eligibility, Consent and Enrollment
Medicines Used in This Study
“succinylcholine+saline” and “rocuronium + sugammadex” 
Randomize
(You will be in Group A or Group B)
Group A
1st ECT study:
Muscle Relaxant #1 
(succinylcholine+saline)
↓
2nd ECT study:
Muscle Relaxant #2        
(rocuronium + sugammadex)
Group B
1st ECT study:
Muscle 
Relaxant #2
(rocuronium + sugammadex)
↓
2nd ECT study:
Muscle Relaxant #1 
(succinylcholine+saline)


[January, 2018]
PAGE 4 OF 8
How long will I be in the study?
Participation in the study will take place in two of your ECT treatments. We would like to keep 
track of your medical condition for 24 hours after the treatment. We would like to do this by 
calling you on the telephone the next day to see how you are doing.   
Can I stop being in the study?
Yes. You can decide to stop at any time. Tell the study doctor if you are thinking about stopping 
or decide to stop. He or she will help you to stop in participation. 
The study doctor may stop you from taking part in this study at any time if he/she believes it is in 
your best interest, if you do not follow the study rules, or if the study is stopped.
What side effects or risks can I expect from being in the study?
You may have side effects while on the study. Everyone taking part in the study will be watched 
carefully for any side effects. However, doctors don't know all the side effects that may happen.  
Side effects may be mild or very serious. Your health care team may give you medicines to help 
lessen side effects. Many side effects go away soon after you stop taking the medication. In some 
cases, side effects can be serious, long lasting, or may never go away. 
You should talk to your study doctor about any side effects you experience while taking part in 
the study.
Risks and side effects related to rocuronium include those, which are:

Allergic reactions: a risk of having an abnormal reaction of the immune system to the
medication. Patients will be observed for an appropriate period of time after
administration.

Muscle weakness.

Conditions / Drugs may cause increased response or resistance to muscle relaxation.
Risks and side effects related to sugammadex include those, which are:
Likely

Nausea or vomiting was reported in 12 to 26% of people having surgery.

Increases in the blood clotting time of up to 25% was reported for up to 1 hour in healthy
volunteers.

Respiratory function monitoring and support is mandatory for patients until adequate
breathing is recovered.


[January, 2018]
 
PAGE 5 OF 8
Less Likely 

Insomnia was reported in 5% of surgical patients. 
Rare but serious

Allergic reaction has occurred in 0.3% of healthy volunteers. Patients will be observed for 
an appropriate period of time after administration.

Slow down of heart rate has been observed within minutes after administration. We will 
monitor for heart rate and blood pressure changes and administer treatment if clinically 
significant slow heart rate is observed.
Waiting times for re-administration of neuromuscular blocking agent for an emergency 
surgery within 24 hours after the study:  

A minimum waiting time is 5 minutes and rocuronium 1.2 mg/kg is to be administered.  
The onset of neuromuscular blockade from rocuronium  may be delayed and the duration 
of neuromuscular blockade may be shortened.  The recommended waiting time in patients 
with mild or moderate renal impairment for re-use of 0.6 mg/kg rocuronium after reversal 
should be 24 hours. If a shorter waiting time is required, the rocuronium dose for a 
new neuromuscular blockade should be 1.2 mg/kg.
For more information about risks and side effects, ask your study doctor.
Are there benefits to taking part in the study?
There may be no direct benefit to you from participating in this study.  However, this study will 
help doctors learn more about sugammadex application in ECT, and it is hoped that this 
information will help in the treatment of future patients undergoing ECT treatment.
What other choices do I have if I do not take part in this study?
Your other choices may include:

Getting treatment or care without being in a study. 
Please talk to your doctor about your choices before deciding if you will take part in this study.
How will information about me be kept confidential?
Participation in research involves some loss of privacy.  We will do our best to make sure that 
information about you is kept confidential, but we cannot guarantee total privacy.  Some 
information from your medical records will be collected and used for this study.    Your signed 
consent form and some of your research tests will be added to your UCSF medical record.  
Therefore, people involved with your future care and insurance may become aware of your 


[January, 2018]
PAGE 6 OF 8
participation and of any information added to your medical record as a result of your 
participation.  Study tests and information gathered directly from you by the researchers will be 
part of your research records but will not be added to your medical record.  Your personal 
information may be given out if required by law.  If information from this study is published or 
presented at scientific meetings, your name and other personal information will not be used.
Authorized representatives from the following organizations may review your research data for 
the purpose of monitoring or managing the conduct of this study:

Representatives of the Sponsor: Merck & Co, Inc.

Representatives of the University of California
Will any research-related cost be billed to me?
No.    The sponsor will provide sugammadex at no cost to you.
Will I be paid for taking part in this study?
You will not be paid for taking part in this study. In appreciation for your participation, and to 
help cover your parking or transportation expense, you will be given a prepaid debit card of 
$20.00 after each study visit is completed. 
What happens if I am injured because I took part in this study?
It is important that you tell your study doctor, Dr. Lee, Dr. Miller, Dr. Li, Dr. Marton or Dr. 
Saunders, if you feel that you have been injured because of taking part in this study. You can tell 
the doctors in person or call the study coordinator at (415) 476-1131. Treatment and 
Compensation for Injury:  If you are injured as a result of being in this study, the University of 
California will provide necessary medical treatment.  The costs of the treatment may be billed to 
you or your insurer just like any other medical costs, or covered by the University of California 
or the study sponsor Merck & Co, Inc., depending on a number of factors.  The University and 
the study sponsor do not normally provide any other form of compensation for injury.  For 
further information about this, you may call the office of the Institutional Review Board at 415- 
476-1814.
What are my rights if I take part in this study?
Taking part in this study is your choice. You may choose either to take part or not to take part in 
the study. If you decide to take part in this study, you may leave the study at any time. No matter 
what decision you make, there will be no penalty to you and you will not lose any of your regular 
benefits. Leaving the study will not affect your medical care. You can still get your medical care 
from our institution. 
We will tell you about new information or changes in the study that may affect your health or 
your willingness to continue in the study.


[January, 2018]
PAGE 7 OF 8
In the case of injury resulting from this study, you do not lose any of your legal rights to seek 
payment by signing this form.
Who can answer my questions about the study?
You can talk to your study doctor about any questions, concerns, or complaints you have about 
this study.  Contact your study doctor(s) Dr. Lee, Dr. Miller, Dr. Li, Dr. Marton, or Dr. Saunders, 
in person.  
If you wish to ask questions about the study or your rights as a research participant to someone 
other than the researchers or if you wish to voice any problems or concerns you may have about 
the study, please call the office of the Institutional Review Board at 415-476-1814 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law.  This Web site will not include information that can identify you.  At most, the 
Web site will include a summary of the results.  You can search this Web site at any time. 
************************************************************


PAGE 8 OF 8
CONSENT
You have been given copies of this consent form and the Experimental Subject's Bill of Rights to 
keep.
You will be asked to sign a separate form authorizing access, use, creation, or disclosure of 
health information about you.]
PARTICIPATION IN RESEARCH IS VOLUNTARY. You have the right to decline to 
participate or to withdraw at any point in this study without penalty or loss of benefits to which 
you are otherwise entitled.
If you wish to participate in this study, you should sign below.
Date
Participant's Signature for Consent
Date
Person Obtaining Consent