A Double-Blind, Randomized, Crossover Design Study To Compare The Rocuronium Reversal By Sugammadex To Succinylcholine For Electroconvulsive Therapy (ECT)
Phase: PHASE2
Conditions: Neuromuscular Blockade
Sponsor: University of California, San Francisco

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 
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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.