Conditions: Microlaryngoscopy Rigid Bronchoscopy
Keywords: deeply anesthetized ideal surgical exposure muscle relaxation Adults
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 79
Healthy volunteers: yes

Brief summary:
Use of Muscle relaxant and reversal with Sugammadex at end of airway procedures will reduce the time to extubation after end of procedure

Detailed description:
This is a prospective, clinical interventional, randomized single blinded single center study.

Hypotheses:

Primary Hypothesis: Use of Muscle relaxant and reversal with Sugammadex at end of airway procedures will reduce the time to extubation after end of procedure

Secondary Hypotheses:

Surgeon will report optimal surgical conditions for ease of exposure

Have less hemodynamic changes in the OR and PACU. ∆ in BP, HR and CO2 from base-line and incidence /frequency of 20% change in BP from baseline vitals (baseline= pre-induction vitals)

Decrease the amount of inhaled anesthetics

Decreased narcotics needed intra-operatively and post operatively

Decrease the total OR time

Subjects will meet ALDRETE PACU discharge criteria quicker in the PACU

Subject will have less adverse events and severe adverse events such as - hypotension, arrhythmia, hypoxia, stridor and re-intubation.

We note that the nurses in PACU will be blinded to whether the subjects were in Group 1 or 2.

Group 1: Inhaled anesthetics: sevoflurane at 1 MAC, remifentanil and intubation with rocuronium at 0.6-1.2 mg/kg (vitals maintained within 20% of baseline). Group 1 will receive reversal with neostigmine (0.04 mg/kg and glycopyrrolate (0.01 mg/kg)

Group 2: Inhaled anesthetics: sevoflurane at 1 MAC, remifentanil and intubation with rocuronium at 0.6 -1.2 mg/kg (vitals maintained within 20% of baseline). Group 2 will receive reversal with sugammadex 4mg/kg

Both groups will receive standard anti-nausea prophylaxis - Ondansetran and Decadran intraoperative.

After induction, the amount of inhaled anesthetic and remifentanil used will be titrated based on hemodynamic parameters (maintained within 20% from baseline) and a BIS monitor.

All subjects will have TOF testing done every 5 minutes throughout the procedure and tabulated in the Electronic Medical Record (EMR).

At the end of the procedure patient will be extubated when the subject meets the following criteria:

Tidal volume : \> 5 cc /Kg Respiratory rate: \>8 /min O2sat \> 95% ON 100% inspired oxygen

With vitals at 20% of baseline. Extubation will begin when the surgeon states, "We are done". This usually coincides with the withdrawal of the scope. The start and end times for extubation will be recorded in the Electronic Medical Record.

The PACU nurses will evaluate ALDRETE discharge criteria and make a note in the electronic medical records for the subject discharge time from PACU. The nurses in PACU will be the only evaluators of the subject who will be blinded to the two groups

Arms:
arm 1: Reversal of Paralysis in Microlaryngoscopy procedures: Inhaled anesthetics: sevoflurane at 1 MAC, remifentanil and intubation with rocuronium at 0.6-1.2 mg/kg (vitals maintained within 20% of baseline). Standard anti-nausea prophylaxis - Ondansetran and Decadran intraoperative.After induction; amount of inhaled anesthetic and remifentanil used will be titrated based on hemodynamic parameters (maintained within 20% from baseline) and a BIS monitor.TOF testing done every 5 minutes:Group 1 will receive reversal with neostigmine (0.04 mg/kg and glycopyrrolate (0.01 mg/kg) arm 2: Reversal of Paralysis in Microlaryngoscopy procedures: Inhaled anesthetics: sevoflurane at 1 MAC, remifentanil and intubation with rocuronium at 0.6-1.2 mg/kg (vitals maintained within 20% of baseline). Standard anti-nausea prophylaxis - Ondansetran and Decadran intraoperative.After induction; amount of inhaled anesthetic and remifentanil used will be titrated based on hemodynamic parameters (maintained within 20% from baseline) and a BIS monitor.TOF testing done every 5 minutes: Group2 will receive reversal with sugammadex 4mg/kg

Interventions: intervention 1: Sugammadex intervention 2: neostigmine intervention 3: glycopyrrolate
Intervention descriptions: intervention 1: receive reversal with sugammadex 4mg/kg intervention 2: receive reversal with neostigmine 0.04 mg/kg intervention 3: receive reversal with glycopyrrolate (0.01 mg/kg)

Protocol document:
Prot_SAP_000.pdf: 
       
 
 
 
Use of Sugammadex for Reversal of Paralysis in Microlaryngoscopy  
 
NCT03111121 
 
01Sep2016 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


       
 
 
 
 
 Investigator Studies Program(MISP)Protocol Template
 
Requirements for Submitting a Full Proposal 
 
 
Section #1 - MISP Protocol Identification 
 
Study Title: 
  
The title of the protocol should include study design, indication and, where applicable, dosage, 
dosage form, and comparative agent(s). 
 
Use of Sugammadex for Reversal of Paralysis in Microlaryngoscopy  
 
 
Request Date: 
September 1 2016 
Institution Name 
 
West Virginia University 
Investigator 
Contact 
Information: 
- Full address  
- Phone No. 
- Fax  No. 
- e-mail address 
 
Pavithra Ranganathan, MD 
1 Medical Center Drive P. O. Box 8255 
Morgantown, WV 26506 
office (304)598-4929 coordinator: (304)598-4737 
Fax (304)-598-4930 
ranganathanp@wvumedicine.org 
 
 
 
 
 
 


       
 
Section #2- Core Protocol 
 
2.1 Objectives & 
Hypotheses  
 
 
 
 
2.1 List the objectives.  
 
Outcome measures measured in the two groups: 
 
Primary outcome 
 
Time to extubation after end of procedure 
 West Virginia University Hospitals use an electronic medical record 
(EMR) to chart the end of the procedure.  When the surgeon states 
“We are done”, always at withdrawal of the scope, extubation 
begins.  From the time we chart end of procedure to the time of 
extubation is the extubation time.  The start and end times for 
extubation will be recorded in the EMR. 
 
The OR time is billed in 15 minute increments and it is a tremendous 
cost saving even for every 5 minutes saved.  It is anticipated that 
extubation using sugammadex will provide at least a 5 min reduction 
in extubation time when compared to the combination of 
neostigmine and glycopyrrolate (8, 11).  This translates to a possible 
45.8 % reduction (12, 13, 14).  
 
 
 Secondary outcomes 
 
1. Subjective interpretation of optimal surgical conditions as evaluated 
by the surgeon for ease of exposure graded from  1-10 ( 1 being 
difficult and 10 being the best  surgical conditions) 
2. Hemodynamic parameters – intra-op and post-op. ∆ in BP, HR and 
CO2  from base–line and incidence /frequency of 20% change in BP 
from baseline vitals ( baseline= pre-induction vitals) 
3. Respiratory parameters – intra op and post op 
4. Inhaled anesthetic concentration  intra-op 
5. Narcotics required intra op and post op  
6. Total OR time 
7. Time taken to meet ALDRETE criteria in PACU 
8. Time to discharge from PACU 
9. Any adverse event and severe adverse events such as - hypotension, 
arrhythmia, hypoxia, stridor and re-intubation will be compared in 
both groups 


       
2.1.1 List the clinical hypotheses.  
 
Hypotheses: 
 
Primary Hypothesis: Use of Muscle relaxant and reversal with 
Sugammadex at end of airway procedures will reduce the time to 
extubation after end of procedure 
 
 
Secondary Hypotheses:            
 
➢ Surgeon will report optimal surgical conditions for ease of exposure 
➢ Have less hemodynamic changes in the OR and PACU. ∆ in BP, HR and 
CO2  from base–line and incidence /frequency of 20% change in BP 
from baseline vitals (baseline= pre-induction vitals) 
➢ Decrease the amount of inhaled anesthetics  
➢ Decreased narcotics needed intra-operatively and post operatively 
➢ Decrease the total OR time 
➢ Subjects will meet ALDRETE PACU discharge criteria quicker in the 
PACU  
➢ Subject will have less adverse events and severe adverse events such 
as - hypotension, arrhythmia, hypoxia, stridor and re-intubation. 
 
2.2 Background & 
Rationale, 
Significance of 
Selected Topic & 
Preliminary Data  
 
Microlaryngoscopy and rigid bronchoscopy for vocal cord and tracheal 
procedures causes an intense sympathetic response during the procedure 
(1). Abrupt increases in heart rate, blood pressure can be seen in these 
procedures(1). Patients have to be extremely still for these highly stimulating 
procedures and hence have to be deeply anesthetized(2) (3). Ideal surgical 
exposure often depends on relaxation of muscles of mastication. Most of 
these procedures are done as outpatient procedures and many of these 
patients have significant co-morbidity. 
Deeply anesthetizing these patients can cause profound hypotension which 
can worsen the medical status of the patient and have longer PACU stay and 
can cause increased post-operative complications. 
Muscle relaxation with non-depolarizing muscle relaxants are rarely used in 
these procedures as the duration of action of the muscle relaxant is 
significantly longer than the actual procedure and time to extubation from 
end of procedure is significantly longer than without using muscle relaxation 
or a Succinylcholine drip.(4)  
Muscle relaxants are synergistic with inhaled anesthetics, and narcotics. 
Hence, the total amount of anesthetics and narcotics used can be 
significantly reduced when combined with muscle relaxants if we are able to 


       
fully reverse the paralysis at the end of the procedure.(5) 
 
2.3 Study Design 
 
 
This is a prospective, clinical interventional, randomized single blinded single 
center study.  We note that the nurses in PACU will be blinded to whether 
the subjects were in Group 1 or 2. 
 
After IRB approval, subjects will be consented in the clinic by the PI or CO-I 
for the study.  
 
After written consent is obtained and a copy provided to the subject; the 
following inclusion and exclusion criteria will be reviewed. The subject must 
meet all inclusion criteria and no exclusion criteria to qualify for the 
treatment phase. The subject that does not qualify will not be included in 
this study. 
Inclusion Criteria: 
➢ Age 18 years or older,  
➢ ASA physical status I-III 
➢ Ability to give written informed consent.  
 
Exclusion criteria: 
➢ Known or suspected neuromuscular disease/pre-existing weakness, 
➢ Creatinine clearance less than 30 ml/min,  
➢ Bradycardia of less than 40 beats/min, 
➢ Pregnancy, breast feeding women, 
➢ Known or suspected allergy to BRIDION® (sugammadex), neostigmine 
or rocuronium. 
➢ Patients with contraindications towards sugammadex, neostigmine 
or rocuronium 
➢ Patients included in another trial within the last 30 days 
➢ Patients with legal guardians or surrogate decision making 
➢ Patients who refuse to use non-hormonal contraceptive method or 
back-up method of contraception (such as condoms and spermicides) 
for the next 7 days if receiving sugammadex.  Ref (6)  
 
 
Patients will be randomized, using a block randomization scheme, to one of 
the two anesthetic groups.  The block randomization scheme will use 
random block sizes varying from 2 to 6 patients per block.  Subjects will 


       
receive a unique study id number (subject 1: i.e. 0001-{3 initial i.e. A-B-C}).  
The randomization scheme will be developed by the statistician; the master 
list of study ids and reversal treatment allocations will be held by the PI and 
research coordinator.  Strict adherence to the sequence of treatment 
allocations will be maintained. 
 
Group 1: Inhaled anesthetics: sevoflurane at 1 MAC, remifentanil and 
intubation with rocuronium at 0.6-1.2 mg/kg (vitals maintained within 20% 
of baseline).  Group 1 will receive reversal with neostigmine (0.04 mg/kg and 
glycopyrrolate (0.01 mg/kg)  
 
Group 2: Inhaled anesthetics: sevoflurane at 1 MAC, remifentanil and 
intubation with rocuronium at 0.6 -1.2 mg/kg (vitals maintained within 20% 
of baseline). Group 2 will receive reversal with sugammadex 4mg/kg  
 
Both groups will receive standard anti-nausea prophylaxis – Ondansetran 
and Decadran intraoperative. 
 
After induction, the amount of inhaled anesthetic and remifentanil used will 
be titrated based on hemodynamic parameters (maintained within 20% from 
baseline) and a BIS monitor.  
 
All subjects will have TOF testing done every 5 minutes throughout the 
procedure and tabulated in the Electronic Medical Record (EMR). 
 
At the end of the procedure patient will be extubated when the subject 
meets the following criteria: 
 
Tidal volume : > 5 cc /Kg 
Respiratory rate: >8 /min 
O2sat > 95% ON 100% inspired oxygen 
 
With vitals at 20% of baseline.  Extubation will begin when the surgeon 
states, “We are done”.  This usually coincides with the withdrawal of the 
scope.  The start and end times for extubation will be recorded in the 
Electronic Medical Record. 
 
 
The PACU nurses will evaluate ALDRETE discharge criteria and make a note 
in the electronic medical records for the subject discharge time from PACU. 
The nurses in PACU will be the only evaluators of the subject who will be 
blinded to the two groups 
 
 


       
Independent Data and Safety Committee Monitoring: 
Data and safety monitoring is a requirement of our institutional IRB (WVU 
IRB) and is standard for all clinical studies.  Independent Data and Safety 
Monitoring Committee: Individuals not involved with the study will review 
the data and make recommendations to continue or stop the study to the 
Principal Investigator.  
 
Following the WVU IRB Independent Data and Safety Monitoring Plan, a 
quality assurance audit will be performed by the IDSMC when 20% of the 
patients have been recruited (n=17).  This audit will include, but not be 
limited to, the review of informed consent process, eligibility confirmation, 
adherence to protocol procedures and treatment plans, pharmacy records 
and storage, and regulatory documentation. Adverse events and severe 
adverse events such as - hypotension, arrhythmia, hypoxia, stridor and re-
intubation will be compared in both groups. 
 
No analysis related to or involving the primary outcome is required or will 
be performed at this time.  
 
ADVERSE EVENT ASSESSMENT: any unfavorable and unintended medical 
occurrence, symptom or disease temporally associated with the use of a 
medical treatment of the subjects whether or not it is associated related to 
the medical treatment. The Principal Investigator will identify and make 
adverse events assessments. Adverse events and severe adverse events such 
as - hypotension, arrhythmia, hypoxia, stridor and re-intubation will be 
compared in both groups. 
 
 
SINGLE BLIND: The nurses in PACU will be the only evaluators of the subject 
who will be blinded to the two groups. The PACU nurses will evaluate 
ALDRETE discharge criteria and make a note in the electronic medical 
records for the subject discharge time from PACU. 
 
Subject total: 84 completed 
 
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 subjects.  At most, the Web site will 
include a summary of the results. 
 
 


       
2.4 Study Flowchart 
 
After contract signed and IRB approval 
 
 
 
Timetable of Investigation: 
 
Year 0.25 
September 
2016 – 
December 
2016 
Year 1 
January 2017 – December 2017 
 
Q4 
Q1 
Q2 
Q3 
Q4 
IRB approval/ 
Renewal 
 
 
 
 
 
Subject 
Screening/Enrollment 
 
 
 
 
 
Data Collection 
 
 
 
 
 
Statistical Analysis 
 
 
 
 
 
Writing/Presentation 
 
 
 
 
 
 
 
 
2.5 Study 
Procedures 
 
Screening: After IRB approval, Subjects will be consented in the clinic by 
the PI or CO-I for the study.  
 
After consenting: The following inclusion and exclusion criteria will be 
reviewed. The subject must meet all inclusion criteria and no exclusion 
criteria to qualify for the treatment phase. The subject that does not qualify 
will not be included in this study. 
 
Inclusion Criteria: 
➢ Age 18 years or older,  
➢ ASA physical status I-III 
➢ Ability to give written informed consent.  
 
Exclusion criteria: 
➢ Known or suspected neuromuscular disease/pre-existing weakness, 
➢ Creatinine clearance less than 30ml/min,  
➢ Bradycardia of less than 40 beats/min, 
➢ Pregnancy, breast feeding women, 
➢ Known or suspected allergy to BRIDION® (sugammadex), neostigmine 
or rocuronium. 
➢ Patients with contraindications towards sugammadex, neostigmine 


       
or rocuronium,  
➢ Subjects included in another trial within the last 30 days 
➢ Patients with legal guardians or surrogate decision making.  
➢ Patients that refuses to use non-hormonal contraceptive method or 
back-up method of contraception (such as condoms and spermicides) 
for the next 7 days if receiving sugammadex 
 
Treatment Phase: Surgery 
Subjects will receive a unique study id number (subject 1: i.e. 0001-{3 initial 
i.e. A-B-C}) if surgery is performed. 
 
Patients will be randomized, using a block randomization scheme, to one of 
the two groups, as outlined in the Study Design section.  Strict adherence to 
the sequence of treatment allocations will be maintained.  
 
Group 1: Inhaled anesthetics: sevoflurane at 1 MAC, remifentanil and 
intubation with rocuronium at 0.6-1.2 mg/kg (vitals maintained within 20% 
of baseline).  Group 1 will receive reversal with neostigmine (0.04 mg/kg and 
glycopyrrolate (0.01 mg/kg)  
 
Group 2: Inhaled anesthetics: sevoflurane at 1 MAC, remifentanil and 
intubation with rocuronium at 0.6 -1.2 mg/kg (vitals maintained within 20% 
of baseline). Group 2 will receive reversal with sugammadex 4mg/kg  
 
Both groups will receive standard anti-nausea prophylaxis – Ondansetran 
and Decadran intraoperative. 
 
After induction; amount of inhaled anesthetic and remifentanil used will be 
titrated based on hemodynamic parameters (maintained within 20% from 
baseline) and a BIS monitor.  
 
All subjects will have TOF testing done every 5 minutes throughout the 
procedure and tabulated in the EMR. 
 
 
Follow-Up: PACU 
 
The PACU nurses will evaluate ALDRETE discharge criteria and make a note 
in the electronic medical records for the subject discharge time from PACU. 
The nurses in PACU will be the only evaluators of the subject who will be 
blinded to the two groups 
 
Adverse events and serious adverse events such as - hypotension, 
arrhythmia, hypoxia, stridor and re-intubation will be followed until 


       
resolution or 30 days post treatment by phone call from research 
coordinator (16). 
 
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 subjects.  At most, the Web site will 
include a summary of the results. 
 
 
Subject total: 84 completed 
 
2.6 Study Duration 
The estimate time for subject enrollment is 12 months, publication and 
presentation of data will follow completion of data analysis. 
 
2.7 Statistical 
Analysis and 
Sample Size 
Justification  
Power/Sample Size: 
 
All patients have a clearly defined time at which extubation begins and ends 
(See Section 2.3, Study Design).  There will be no patients with unobserved 
end points (e.g. no loss to follow-up, attrition, or right censoring).  
Additionally, the Data and Safety Monitoring does not require the analysis of 
the primary research question prior to the completion of the study (See 
Section 2.3, Study Design, Data and Safety Monitoring subsection).   
 
Based on these considerations, powering for the primary outcome of 
extubation time used the log-rank test, Schoenfeld’s method, and balanced 
allocation of patients to each group (9-10).  With minimum power of 80%, an 
alpha-level of 0.05, and an effect size of 0.542, a total of 84 patients are 
required providing 42 patients per group.   
 
The effect size was derived using median times-to-extubation to estimate 
the hazard ratio.  An estimate of the median extubation time for 
sugammadex is 6.4 minutes (8, 11) with a minimum differential of 5.4 
minutes for the combination of neostigmine and glycopyrrolate (i.e. 11.8 
min).  The 5.4 min differential is twice the differential between sugammadex 
and pyridostigmine (8), and is motivated by longer extubation times for 
neostigmine and glycopyrrolate when compared against pyridostigmine (15).  
The anticipated minimal differential has positive clinical and financial 
ramifications (Section 2.1 Objective & Hypotheses). 
 
 
 
 
 
 
Statistical Analysis: 
 


       
We will use univariate statistics (e.g. mean, median, standard deviation, 
interquartile range) to summarize the collected data.  Balance between the 
two groups for key patient variables (see Section 2.1 for examples) will be 
assessed using a two-sided two-sample t-test using unequal variances and 
the Welch modification to the degrees of freedom.  For categorical variables, 
the Chi-square test will be used.  If non-parametric tests or exact methods 
are required, we will use the Mann-Whitney U test and the Fisher-Freeman-
Halton exact test respectively. 
 
The primary comparison of extubation time between the two groups will be 
assessed using the Kaplan-Meier method and log-rank test.  Statistical 
significance will be assessed using a two-sided test with an alpha-level of 
0.05. All statistical analysis will be performed using the R software 
environment for statistical computing and graphics (7). 
 
2.8 Specific Drug 
Supply 
Requirements  
Phase 4 study: Drug: BRIDION®, sugammadex, will be supplied by Merck: 
Budget for cost for research in-patient pharmacist to receive drug from 
Merck, dispense drug, keep research accountability, and keep blind for 
research study is included at $70/subject. 
2.9 Adverse 
Experience 
Reporting 
Phase 4 study: FDA policy on reporting Form 3500 
 
 
2.10 Itemized Study 
Budget  
Please see attached budget  
2.11 References 
(1) Cardiac complications of microsurgery of the larynx: etiology, incidence 
and prevention. Strong MS, Vaughan CW, Mahler DL, Jaffe DR, Sullivan RC, 
Laryngoscope. 1974 Jun; 84(6):908-20. 
 
(2) Anesthesia for laryngoscopy. Benjamin B. Ann Otol Rhinol Laryngol. 1984 
Jul-Aug; 93(4 Pt 1):338-42.   
 
(3) Effects of anesthetic technique on the hemodynamic response to 
microlaryngeal surgery. Ayuso A, Luis M, Sala X, Sánchez J, Traserra J Ann 
Otol Rhinol Laryngol. 1997 Oct; 106(10 Pt 1):863-8. 
 
(4) Assessment of depth of anesthesia and postoperative respiratory 
recovery after remifentanil- versus alfentanil-based total intravenous 
anesthesia in patients undergoing ear–nose–throat surgery. Anesthesiology. 
2001; 94:211–7. 
 


       
(5) Basics of Anesthesia–sixth edition Ronald C. Miller page 152 
(pharmacodynamics responses) 
 
(6) Package circular for BRIDION (sugammadex) U.S. approval 2015 
 
(7) R Development Core Team (2016): R: A Language and Environment for 
Statistical Computing, R Foundation for Statistical Computing, Vienna, 
Austria, URL http://www.R-project.org, ISBN 3-900051-07-0. 
 
(8) Eui-Seok Park, Byung Gun Lim*, Won-Joon Lee and Il Ok Lee.  
Sugammadex facilitates early recovery after surgery even in the absence of 
neuromuscular monitoring in patients undergoing laryngeal microsurgery: a 
single-center retrospective study.  BMC Anesthesiology (2016) 16:48.  DOI 
10.1186/s12871-016-0221-2 
 
(9) David W. Hosmer, Stanley Lemeshow, Susanne May (2008),  Applied 
Survival Analysis: Regression Modeling of Time-to-Event Data, 2nd Ed.  Wiley 
Series in Probability and Statistics, John Wiley & Sons, Hobooken, NJ, USA. 
[Section 9.7, pp 340-346] 
 
(10) David Collett (2003), Modelling Survival Data in Medical Research, 2nd 
Ed.  Chapman & Hall/CRC, Boca Raton, Florida, USA.  [Section 10.2.1, pp 302-
304] 
 
(11) Vymazal T, Krecmerova M, Bicek V, Lischke R. Feasibility of full and rapid 
neuromuscular blockade recovery with sugammadex in myasthenia gravis 
patients undergoing surgery – a series of 117 cases. Therapeutics and Clinical 
Risk Management. 2015;11:1593-1596. doi:10.2147/TCRM.S93009. 
 
(12) Paton F1, Paulden M, Chambers D, Heirs M, Duffy S, Hunter JM, 
Sculpher M, Woolacott N 2010 Oct 8.:Sugammadex compared with 
neostigmine/glycopyrrolate for routine reversal of neuromuscular block: a 
systematic review and economic evaluation. Br J Anaesth. 2010 
Nov;105(5):558-67. doi: 10.1093/bja/aeq269. Epub 
 
(13) D Chambers, M Paulden, F Paton,M Heirs, S Duffy, D Craig, J Hunter,J 
Wilson, M Sculpher and N Woolacott: Sugammadex for the reversal of 
muscle relaxation in general anaesthesia: a systematic review and economic 
assessment: Health Technology Assessment 2010; Vol. 14: No. 39 
 
(14)Chambers D1, Paulden M, Paton F, Heirs M, Duffy S, Hunter JM, Sculpher 
M, Woolacott N.:Sugammadex for reversal of neuromuscular block after 
rapid sequence intubation: a systematic review and economic assessment. 
Br J Anaesth. 2010 Nov;105(5):568-75. doi: 10.1093/bja/aeq270. Epub 2010 


       
Oct 11. 
 
(15)Edoardo De Robertis,1 Geremia Zito Marinosci,1 Giovanni Marco 
Romano,1 Ornella Piazza,2 Michele Iannuzzi,1 Fabrizio Cirillo,1 Stefania De 
Simone,3 and Giuseppe Servillo1The use of sugammadex for bariatric 
surgery: analysis of recovery time from neuromuscular blockade and 
possible economic impact: Clinicoecon Outcomes Res. 2016; 8: 317–322. 
Published online 2016 Jun 29.  doi: 10.2147/CEOR.S109951:PMCID: 
PMC4934482:Table 2 : Pharmacological data and costs of reversal drugs 
 
(16)Boon M1, Martini C1, Broens S1, van Rijnsoever E2, van der Zwan T3, 
Aarts L1, Dahan A4: Improved postoperative oxygenation after antagonism 
of moderate neuromuscular block with sugammadex versus neostigmine 
after extubation in 'blinded' conditions: Br J Anaesth. 2016 Sep;117(3):410-1. 
doi: 10.1093/bja/aew246. 
 
 
 
  
2.12 Publication 
Plan 
 
 
Publications in Anesthesiology Journal and presentations at ASA meetings in 
fall of 2017 and/or Spring 2018 
 
2.13 Curriculum 
Vitae 
 
Please see Attached in vision tracker  
2.13 Protocol 
Submission for 
Investigator-
Initiated Studies  
U.S. protocols should be submitted by US investigators directly or through 
the Global Research Specialist at  www.merckiisp.com   
 
Non U.S. protocols should be submitted to the MSD office by the 
investigators. 
 

ICF_001.pdf: 
 
 
 
 
 
Use of Sugammadex for Reversal of Paralysis in Microlaryngoscopy 
 
 
NCT03111121 
 
01Sep2016 
 


 
Human Research Protocol 
More Than Minimal Risk Form 
(With HIPAA) 
 
 
More than Minimal Risk  
Consent and HIPAA Form 
 
 
 
Principal Investigator 
Department 
Study Title 
Pavithra Ranganathan, MD 
Anesthesiology 
Use of Sugammadex for Reversal of Paral1,1sis in Micro laryngoscopy 
 
Co-lnvestigator(s) 
Kathrine Allen MD; Matthew Ellison MD; Tanya Fancy MD; Jason Paul 
Mcchesney MD; Hassan H. Ramadan MD; Rusha Patel MD; Jason L. Shepherd MD; Walter Kielkowski CRNA; J. 
Sean Morris CRNA; Kelly Myers CRNA; Michael I<. Ritchie, MD; Payam Heiraty, MD; Jeffson Chung MD; Kristin 
Dragan, MD and D. Chad Sizemore, MD 
 
 
 
Sponsor 
 
Contact 
Person: 
Investigator initiated: Merck Investigator Studies Program (MISP) 
 
Pavithra Ranganathan, MD 
1 Medical Center Drive Department of Anesthesiology 
P. 0. Box 8255 Morgantown, WV 26506 
 
This is not a consent form for surgery or anesthesia. Your surgeon and/or anesthesiologist will 
provide a separate consent form for those procedures. 
 
 
 
 
In the event you experience any side effects or injury related to this research, you should contact Dr. 
Ranganathan or Dr. Ellison at (304) 598-4929. (After hours contact: Anesthesia at (304) 598-4000 ext. 76263. If 
you have any questions, concerns, or complaints about this research, you can contact Dr. Ranganathan at 
(304)598-4929. 
 
For information regarding your rights as a research subject, to discuss problems, concerns, or suggestions 
related to the research, to obtain information or offer input about the research, contact the Office of Research 
Compliance at (304) 293-7073. 
In addition, if you would like to discuss problems, concerns, have suggestions related to research, or would like 
to offer input about the research, contact the Office of Research Integrity and Compliance at 304-293-7073. 
 
 
 
West Virginia University 


Human Research Protocol 
 More Than Mlinimal Risk Form 
(With HIPAA) 
 
 
' 
1; 
Introduction 
You,____________________, have been asked to participate in this research study, which has been explained 
to you by ______________________________________________.  This study is being conducted by Dr. 
Ranganathan Department of Anesthesiology at West Virginia University with funding support and Sugammadex 
(Bridion®) provided by Merck Investigator Studies Program. 
 
 
 
Purpose(s) of the Study 
The main purpose for this study is to collect data on the use of muscle relaxants and 2 types of Food And Drug 
Administration (FDA) approved reversal agents (1- Neostigmine, 2- Sugammadex) to see if Sugammadex will  
reduce the time to removal of breathing tube after the end of surgical procedures with micro laryngoscopy 
(examination of the airway, interior of the larynx with a laryngoscope with binocular magnification) as 
explained to you by your surgeon. 
 
Researchers will collect data on the time when the surgeons are done with the procedure to the time the 
breathing tube is removed from the  airway. The surgeons' reports as optimal surgical conditions for ease 
looking at  your airway, changes in vital signs if there is any from your baseline vital signs, amount of 
anesthetics used, total amount narcotics needed intra-operatively and post operatively, the total Operating 
Room time, PACU time and adverse events. 
 
WVU expects to enroll approximately 84 completed subjects. WVU is the only site. 
 
 
Description of Procedures 
This study involves collecting data on subjects that are going to have a procedure that require 
intubation and examination of airway and related airway structures. 
You are eligible to participate  in this study since you  are  going to  have  a  procedure to  look at  your throat,  
vocal cords and voice box structures. You are also eligible because you are 18 years of age or older and don't 
have an allergy to any of the medications that we may use as part of your anesthetic. 
Screening phase:  You  will discuss this consent with the  research staff  in the  clinic or surgery suite. You  may 
take a copy of this form home to read and make a decision prior to your procedure date. 
Participation is voluntary and if you decide to participate please inform the staff who will go through the 
consent process with you. 
 
 
 


Human Research Protocol 
More Than Minimal Risk Form 
(With HIPAA) 
 
 
 
Treatment phase: Surgery 
 
You will have your surgery as your surgeon requires and you will be randomized (like flipping a coin) into 1 of 2 
groups: Both groups will receive standard of care treatments. The research team will collect data on the 
groups. You will be given a unique study ID number, i.e. 0001-ABC, to  help keep your identification confidential. 
The  principal  investigator and study coordinator will have access to the master code that links you to the 
research code. It will be on a computer 
and is password protected. 
 
 
Both groups will receive a standard general anesthetic. Both groups will receive all other standard 
medications given as part of a general anesthetic. 
 
Group 1 will receive reversal of paralysis with a medication called 
neostigmine. Group 2 will receive Reversal of paralysis with a medication 
called Sugammadex. 
Follow-up: 
 
Post anesthesia care unit (PACU): 
The nursing staff will document when you are ready for discharge from this area. These nurses will not know 
what group you are in. That information will be kept confidential and coded. 
You may receive a phone call within 30 days if you have had an adverse event such as low blood pressure, 
palpitations, shortness of breath, low oxygen levels after procedure, or needed to be re-intubated (replace tube  in 
throat  to  help you breath). If  you  have  not  had  an  adverse  event you will  be finished  with  the  study after 
discharge from the  post anesthesia care unit. 
Your participation may be terminated by the investigator  without  regard to  your consent at  any time if the  
investigator feels it is necessary. 
 
 
Risks and Discomforts 
Drugs often have side effects. The drugs used in this program may cause all, some, or none of the side effects 
listed. In addition, there  is always the  risk of  uncommon  or  previously  unknown  side effects.   There  may  be  
reasonably foreseeable invasive or non-invasive risks or discomforts due to your surgery. You will discuss and 
sign a surgery consent with your surgeon. 
 
Neostigmine Side effects 
Serious side effects may include: muscle weakness, slurred speech, vision problems, feeling like you 
might pass out, severe stomach cramps or diarrhea, trouble breathing, cough with mucus, fast or slow 
heart rate, convulsions, 


 
Human Research Protocol 
More Than Minimal Risk Form 
(With HIPAA) 
 
 
Less serious side effects may include: headache, drowsiness, mild nausea, vomiting, gas, urinating more than usual, cold 
sweat, warmth or tingly feeling, mild rash or itching. 
 
Sugammadex Side effects 
Most common side effects seen in >10% of subjects are vomiting, pain, nausea, and head ache. 
Some serious side effects may include slow heart rate, low blood pressure and allergy to the medication. 
 
This study may involve risks to the unborn child. For this reason, women who are pregnant will not be accepted. 
You must use a medically approved method of birth control while you are on this study and 7 days after receiving 
Sugammadex. 
 
 
Men who are able to father a child should never have unprotected sex with a woman while in this study because it is not 
known if the drug is present in semen or sperm. 
 
Alternatives 
You do not have to participate in this study. 
 
Benefits 
You may not receive any direct benefit from this study. The knowledge gained from this study may eventually benefit 
others. 
 
Financial Considerations 
Sugammadex will be provided by Merck Investigator Studies Program at no cost to you, if you receive it. 
There are no special fees for participating in this study, but any expense associated with current therapy or treatment of 
side effects will be billed to you or to your insurance company. 
 
 
Voluntary Compensation 
If you are injured as a result of this research, treatment will be available.  Responsibility for this treatment  will be borne 
by you or your insurance company.  In the event that you are physically injured as a result of participating in this 
research, care will be available. You will, however, be responsible for the charges for the care. There is no commitment 
to provide any compensation for research-related injury. You should realize, however, that you have not released this 
institution from liability for negligence. Please contact the investigator, Ranganathan at 304-598-4929 if you are injured 
or for further information. 
 
Confidentiality 
Any information about you that is obtained as a result of your pa1iicipation in this research will be kept as confidential as 
legally possible. Your research records and test results, just like hospital records, may be subpoenaed by court order or 


Human Research Protocol 
More Than Minimal Risk Form 
(With MIPAA) 
 
 
may be inspected by the study sponsor or federal regulatory aut11oriiies (including the FDA if applicable) without your 
additional consent. 
 
A description of this clinical trial will be available on www.ClinicalTrials.gov, as required by US law. This website will not 
include information that can identify you. At most, the website will include a summary of the results. You can search this 
website at any time. 
 
HIPAA 
We know that information about you and your health is private. We are dedicated to protecting the privacy of that 
information. Because of this promise, we must get your written authorization (permission) before we may use or 
disclose your protected health information or share it with others for research purposes. 
 
You can decide to sign or not to sign this authorization section. However, if you choose not to sign this authorization, 
you will not be able to take part in the research study. Whatever choice you make about this research study will not 
have an effect on your access to medical care. 
Persons/Organizations Providing the Information 
Patient/West Virginia University Hospitals 
 
Persons/Organizations Receiving the Information 
 
o 
The research site(s) carrying out this study. This includes UHA or UHA Affiliated, WVU, WVU Hospitals. 
It also includes each site's research staff and medical staff 
o 
Health care providers who provide services to you as part of this research study. 
o 
The United State Department of Health and Human Services (which includes the National Institutes of 
Health (NIH), Food and Drug Administration (FDA)) and other groups that have the right to use the 
information as required by law. 
o 
Merck and the people and companies that they use to oversee, manage, or conduct the research. 
o 
The members and staff of any Institutional Review Board (IRB) that oversees this research study. 
o 
West Virginia University Office of Research Compliance and Office of Sponsored Programs. 
The Following Information Will Be Used 
Information from your existing medical records and new information about you that is created or collected during the 
study such as: history and physicals, clinic visit notes, nursing and staff notes, laboratory results, x-rays, El<G results, 
demographic data, pulmonary tests, imaging scans and study forms. 
 
 
 
 
\'


 
 
Human Research Protocol 
More Than Minimal Risk form 
(With HIPAA) 
 
 
 
 
 
The Information is Being Disclosed for the Following Reasons 
 
o 
Review of your data for quality assurance purposes 
c 
Publication of study results (without identifying you) 
 
 
 
You May Cancel this Authorization at Any Time by Writing to the Principal Investigator 
Pavithra Ranganathan, MD at 1 Medical Center Drive Department of Anesthesiology P. 0. Box 8255 Morgantown, 
WV 
26506 
If you cancel this authorization, any information that was collected already for this study cannot be 
withdrawn. Once information is disclosed, according to this authorization, the recipient may re disclose it 
and then the information may no longer be protected by federal regulations. 
You  have a  right to see  and  make copies of your medical  records. You will  not  be  able to see or copy 
your records related to the study until the sponsor has completed all work related to the study. At that 
time you may ask to see the  study doctor's files related to your participation in the  study and  have 
the  study doctor correct any information about you that is wrong. 
 
This authorization will expire at the end of the study unless you cancel it before that time. 
 
Voluntary Participation 
Participation in this study is voluntary.  You are  free to withdraw your consent to participate in this study at any 
time. 
 
Refusal to participate or withdrawal will not affect your care and will involve no penalty to you. Refusal to 
participate or withdrawal will not affect your future care, or your employee status at West Virginia University. 
In the event new information becomes available that may affect your willingness to participate in this 
study, this information will be  given to you so that you can make an informed decision about whether or 
not to continue your participation. 
 
You have been giv n the opportunity to ask questions about the research, and you have received 
answers concerning areas you did not understand. 
 
Upon signing this form, you will receive a copy. 
 
I willingly consent to participate in this research. 


Human Research Protocol 
More Than Minimal Risk Form 
(With MIPAA) 
 
 
 
V 
 
 
 
 
Signatures 
 
 
Signature of 
Subject,  
 
 
 
 
  
______________________________ 
Date 
Time 
              Printed Name 
 
 
The participant has had the opportunity to have questions addressed. The participant 
willingly agrees to be in the study. 
 
Signature of Investigator or Co-Investigator 
_______________________________________________________________________________________________________________________________________________ 
 
 
Date 
Time 
 
Printed Name ____________________________________________________________________