Anesthesiological Management of Ventilation With Laryngeal Mask in Patients Undergoing Endoscopic Retrograde Cholangiopancreatography (ERCP) and Endoscopic Ultrasound Procedures
Phase: NA
Conditions: Anesthesia, Airway Device, C.Surgical Procedure; Gastrointestinal
Sponsor: Ospedale San Raffaele

CLINICAL TRIAL PROTOCOL 
 
STUDY NUMBER:  
 
STUDY TITLE: Anesthesiological management of ventilation with laryngeal mask in patients undergoing endoscopic 
retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound procedures. 
 
VERSION NUMBER: 1   
 
 
 
 
 
 
DATE: December 28th, 2017 
 
COMPOUND: Laryngeal mask versus no device in ERCP and endoscopic ultrasound procedures 
 
Promoter: xxx 
 
Principal Investigator: xxx 
 
 
 
 
 
 
Signature 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                  ________________________________ 
 

Seomask 
version n° 1  
 
 
 
December 28th, 2017 
 
 
2
 
TABLE OF CONTENTS 
1. 
SYNOPSIS ................................................................................................................................................ 3 
2. 
FLOW CHART .......................................................................................................................................... 6 
3. 
INTRODUCTION AND RATIONALE ........................................................................................................... 7 
4. 
STUDY OBJECTIVES ................................................................................................................................. 8 
5. 
STUDY DESIGN ........................................................................................................................................ 8 
6. 
SELECTION OF PATIENTS ........................................................................................................................ 8 
7. 
TREATMENTS .......................................................................................................................................... 8 
8. 
STUDY PROCEDURES .............................................................................................................................. 9 
9. 
PATIENT SAFETY ..................................................................................................................................... 9 
10. 
TEMPORARY OR DEFINITIVE TREATMENT DISCONTINUATION .............................................................. 9 
11. 
STATISTICAL CONSIDERATIONS .............................................................................................................. 9 
12. 
ETHICAL AND REGULATORY CONSIDERATIONS .................................................................................... 10 
13. 
DATA MANAGEMENT ........................................................................................................................... 10 
14. 
DATA PROTECTION ............................................................................................................................... 10 
15. 
CLINICAL TRIAL RESULTS ....................................................................................................................... 10 
16. 
BIBLIOGRAPHIC REFERENCES ............................................................................................................... 10 
 
 

Seomask 
version n° 1  
 
 
 
December 28th, 2017 
 
 
3
  
1. SYNOPSIS  
COMPOUND:  Laryngeal mask versus no device in endoscopic retrograde cholangiopancreatography (ERCP) 
and endoscopic ultrasound procedures 
STUDY No.: Seomask1 
 
Anesthesiological management of ventilation with laryngeal mask 
in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic 
ultrasound procedures 
TRIAL LOCATION 
P.I. Dott. xxx 
  
Department of Anesthesia and Intensive Care  
STUDY OBJECTIVE(S)  
Primary: Partial Pressure of Carbon Dioxide (PaCO2) at the end of the 
endoscopic procedure 
  
Secondary:                            
- Number needing pressure support ventilation (PSV) in the treatment group 
- pH, Partial Pressure of Oxygen (PaO2) at the end of the procedure                    
-Time to recover after the procedure 
-Satisfaction of the procedure operator 
-Satisfaction of the patient 
STUDY DESIGN  
Single Centre 
Comparative  
No profit 
1:1 randomized  
Single blind (patient) 
STUDY POPULATION             
Main selection criteria: 
INCLUSION CRITERIA                                                                                                       
-age >18 years 
-written informed consent 
-elective  ERCP and endoscopic ultrasound procedure                                             
EXCLUSION CRITERIA 
-pregnancy 
-contraindication to propofol  administration 
-contraindication to mask insertion (e.g. malformation) 
- emergency operation (not scheduled)  
- preexisting causes of hypoventilation (e.g. cronic obstructive pulmonary 
disease, neuromuscular disease…) 
Total expected number of 
patients: 
60 
INVESTIGATIONAL 
PRODUCT(S) 
 
LMA® Gastro™ Cuff Pilot™ 
The device allows the access to the esophagus with separation of the 
airways. 
The ventilation tube has an anatomical shape and a laryngeal mask (LMA) at 
the extremity. The cuff is adaptable to the pharyngeal shape with an open in 
front of the larynx. It has a parallel channel for the endoscope that ends 
under the cuff at the level of the upper esophageal sphincter (UES). 
EFFICACY CRITERIA 
Primary: Partial Pressure of Carbon Dioxide (PaCO2) at the end of the 
endoscopic procedure  

Seomask 
version n° 1  
 
 
 
December 28th, 2017 
 
 
4
  
Secondary:       
- Number needing pressure support ventilation (PSV) in the treatment group   
- pH and PaO2 at the end of the procedure                                                                 
-Time to recover after the procedure 
-Satisfaction of the procedure operator 
-Satisfaction of the patient 
- Completion of the endoscopic procedure 
SAFETY CRITERIA 
No risk for the study subjects is expected 
STUDY PROCEDURES 
Patients undergoing ERCP and endoscopic ultrasound will be screened the 
day before the procedure during the routine anaesthesiological visit. Eligible 
patients will be enrolled. 
Immediately before the procedure patients will be allocated according to a 
simple randomization list to a treatment group and a control group. Patients 
will be blinded about the treatment, since they will be unconscious during 
the procedure (single blind study). 
Patients in the control group will receive the standard anaesthesiological 
management of ERCP-patients, which is based on total intravenous 
anesthesia with propofol target controlled infusion (TCI) in spontaneous 
breathe without any airway devices. 
In patients in the treatment group a  laryngeal mask (LMA) specifically 
designed to permit gastroiontestinal endoscopy will be inserted after the 
induction of sedation. This allows for expiratory end tidal CO2 (ETCO2) 
monitoring and assisted ventilation if needed. 
In both groups anesthesia induction and maintenance will be performed 
according to a TCI protocol with a tailored site-effect target between 4 and 6 
mcg/ml.  Treatment group will receive PSV in case of ETCO2 raising above 50 
mmHg. At the end of the endoscopic procedure an arterial gas analysis will 
be performed.  Patients will be awakened as usual and then monitored in 
recovery room until full recovery. Data will be collected intraoperatively and 
during the recovery room stay.  
The study will start after Ethical Committee approval. 
STATISTICAL 
CONSIDERATIONS 
The PaCO2 in the treatment group is expected to be around 45 mmHg, due 
to the study design.  A clinically significant hypoventilation is indicated by a 
PaCO2 around 50 mmHg and could be expected in the control group. We aim 
at observing such a 5 mmHg PaCO2 difference between groups with power 
90% and alpha=0.05.  PaCO2 SD during sedation is considered around 5 
mmHg 1.  
This yields a calculated  44 patients (22 per group). 
We decide to enroll 60 patients (30 per group) taking into account dropouts 
and possible  non-normality. 
Continuous data will be reported as mean±SD[median(IQR)] and compared 
with the Student t tests on the equality of means or with the Wilcoxon rank-
sum test (Mann-Whitney  two-sample statistic) if not normal. Normality will 
be tested by visual inspection and with the Shapiro-Wilk W test for 
normality. 
Categorical data will be reported as number(percentage) and compared with 
the Pearson's chi-squared test Fisher's exact test if appropriate. 
DURATION OF STUDY 
PERIOD 
6 months 
 
 
 

Seomask 
version n° 1  
 
 
 
December 28th, 2017 
 
 
5
 
 
 
 

Seomask 
version n° 1  
 
 
 
December 28th, 2017 
 
 
6
2. FLOW CHART 
 
 
SCREENING PHASE 
(day -1) 
TREATMENT PHASE 
(day 0) 
RECOVERY ROOM 
PHASE 
(day 0) 
Clinical Examination 
X 
X 
X 
Laboratory Testing 
(and pregnancy test) 
X 
X 
 
Inclusion/Exclusion 
Criteria 
X 
X 
 
Informed Consent 
X 
 
 
Randomization 
 
X 
 
Investigational Device 
Use 
 
X 
 
AE /SAE recording 
(if any): 
 
X 
X 
 
 
 

Seomask 
version n° 1  
 
 
 
December 28th, 2017 
 
 
7
3.  INTRODUCTION AND RATIONALE  
Diagnostic and operative procedures of upper gastrointestinal (GI) tract are very common in all patients. 
The associated level of discomfort is extremely different and often subjective, but some procedures are 
difficult to tolerate because of long duration, prone position or significant stimulation of the upper airways.  
In case of obstructive jaundice suspicious for pancreatic lesion which needs cythopatologic determination, 
endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound are often performed 
at once. The endoscopic probe is conducted in duodenum, an endoscopic ultrasound and some biopsys are 
performed and then the biliary tract is investigated with a contrast agent injected from the papilla of Vater. 
Ducts dilatation or prosthesis placement can be performed if necessary. The more the complexity, the 
longer the procedure.  
The procedure is generally performed with deep sedation. Many pharmacologic regimens are available and 
described in literature. Our institute adopts propofol target controlled infusion (TCI), setting a tailored 
target between 4 and 6 mcg/ml. This protocol usually guarantees unconsciouseness and unresponsiveness 
of patients. Propofol is a handy intravenous hypnotic drug but the main adverse event is dose-related 
respiratory depression. Pre-existing reasons for hypoventilation can exacerbate this event. Specific 
categories prone to this condition are the elderly and the cronic obstructive pulmonary disease-patients. 
The possibility to ventilate the patient with a pressure support ventilation (PSV) is an interesting 
perspective. Laryngeal mask (LMA) is a useful tool when an invasive ventilation is not necessary and when 
neuromuscular block is not required. 
This specific type of LMA allows to separate the gastric and respiratory tract and, allows the 
anesthesiologist to support patient’s ventilation as (and only if) necessary. 
 
BACKGROUND and PRELIMINARY DATA 
A review of 33.854 GI endoscopy in Scotland underlines  that for upper GI endoscopy in ASA 3-5 patients, 
the participation of an anesthesiologist, particularly for airway management and sedation, is mandatory. 
Complications can occur during the procedure and the percentage of death is 0.059%.2 
A recent trial concerning the use of a gastro-laryngeal tube for airway management versus no devices 
found higher satisfaction, less degree of desaturation and faster recovery after anesthesia in the treatment 
group.3 
Another study regarding a novel method of positive pressure ventilation (mask adaptor) in upper GI 
procedures reported an incidence of 3/30 (10%) carbon dioxide end-tidal (ETCO2) > 50 mmHg4. This value 
exceeds the normal range of  35-45 mmHg and has several physiological implications (e.g. cerebral 
vasodilatation, tachycardia, lethargy) 
 
ORIGINALITY OF THE PROPOSAL 
Patients in spontaneous breathe without airway devices could reach a high level of carbon dioxide (CO2) 
totally unknown to the anesthesiologist which has no tool to measure it. The introduction of a LMA in 
upper GI procedures could improve not only the monitoring but also the management of these patients. 
Literature has very few examples of airway management during GI procedures. Nowadays, new devices 
have been patented and are currently used in anesthesia. Our proposal is to introduce LMA in GI endoscopy 
to improve patient and clinicians satisfaction, reduce procedure-related complications and shorten 
recovery after anesthesia.  
 
MAIN EXPECTED RESULTS AND IMPACT 
This randomized controlled trial aims to demonstrate a beneficial effect of LMA in GI endoscopic 
procedure. In details we hypothesize: 
- a faster recovery because of maintenance of normal level of CO2. 
-a higher satisfaction for patient, anesthesiologist and endoscopic operator because of deep level of 
sedation also in more fragile population 
- an increased safety for all patients and in particular in the specific population at significant risk for 
hypoventilation 

Seomask 
version n° 1  
 
 
 
December 28th, 2017 
 
 
8
The results of this study can support the use of LMA in all ERCP and/or GI endoscopic procedures also in 
other centers.  
 
4. STUDY OBJECTIVES  
 
4.1 Primary 
Partial Pressure of Carbon Dioxide (PaCO2) at the end of the endoscopic procedure  
4.2 Secondary 
Secondary endpoints will be: 
- Number needing pressure support ventilation (PSV) in the treatment group 
- pH and PaO2 at the end of the procedure 
-Time to recover after the procedure 
-Satisfaction of the endoscopy operator 
-Satisfaction of the patient 
 
5.  STUDY DESIGN 
5.1 Description of the protocol  
This is a monocentric randomized controlled trial of superiority of LMA use in GI endoscopic procedures. 
Randomization is centralized. The study is single blind (patient).  The study is no-profit. 
5.2 Duration of study  
Every patients undergoing scheduled ERCP and endoscopic ultrasound will be screened and consecutive 
eligible patients will be enrolled. The study starts after randomization and ends after discharge from the 
recovery room. 
 
6.  SELECTION OF PATIENTS 
6.1 Number of patients planned : 60 
6.2 Inclusion criteria  
-age >18 years 
-written informed consent 
-elective ERCP and endoscopic ultrasound procedures 
6.3 Exclusion criteria  
-pregnancy 
-emergency procedure 
-contraindication to propofol administration 
-contraindication to mask insertion (e.g. malformation) 
-preexisting causes of hypoventilation (e.g. cronic obstructive pulmonary disease, neuromuscular disease…) 
 
7. TREATMENTS  
7.1 Investigational Medicinal Product (IMP)  
All patients in both groups will receive propofol TCI with a tailored target between 4 and 6 mcg/ml until the 
end of the procedure. 
The treatment group will also receive LMA insertion after induction of anesthesia and ETCO2 monitoring. In 
case of hypoventilation with an ETCO2 higher than 50 mmHg the patient will receive PSV to normalize this 
value. 
Both group will receive a laboratory testing (periferal arterial sample) at the end of the procedure, when 
the patient is still sedated, to obtain important data about ventilation. 
7.2 Other products 
Intraoperatively, there will not be any limitation to the use of any drugs as in general practice. 
7.3 Description of blinding methods. 
All the patients will be blinded to treatment assignment for the duration of the study. This study is single 
blind. 
7.4 Method of assigning patients to treatment group (if applicable)  

Seomask 
version n° 1  
 
 
 
December 28th, 2017 
 
 
9
Randomization will be performed centrally by a simple randomization list.   
7.5 Responsibilities  
There is no specific drug under investigation. 
7.6 IMP accountability and compliance  
There is no drug company involved and there is no specific drug under investigation. 
 
8. STUDY PROCEDURES  
Subjects will be allocated according to a simple randomization list. Data will be collected by the 
investigators or trained colleagues.  
After periferal venous catheter insertion and vital parameters monitoring, patients will receive propofol TCI 
with a tailored target between 4 and 6 mcg/ml. The treatment group will receive LMA insertion and ETCO2 
monitoring throughout the procedure. In case of hypoventilation, with an ETCO2 above 50 mmHg, the 
patient will be supported as necessary with PSV. The control group will not receive any airway device, 
according to the standard treatment. At the end of the procedure, both group will receive a laboratory 
testing (periferal arterial sample), when the patient is still sedated. Vital parameters monitoring will 
continue in recovery room. Patients will be discharge as usual with an Aldrete score > 9. 
Data will be collected during the procedure and in recovery room. 
Data will be stored in electronic database without mention to patient’s name. 
8.1 Efficacy 
The primary endpoint of the study will be the PaCO2 at the end of the endoscopic procedure.  
Secondary endpoints will be: 
- Number needing pressure support ventilation (PSV) in the treatment group 
-pH and PaO2 at the end of the procedure 
-Time to recover after the procedure 
-Satisfaction of the procedure operator 
-Satisfaction of the patient 
- Completion of the endoscopic procedure 
 
9. PATIENT SAFETY 
No risk for the study subjects is expected. 
 
10. TEMPORARY OR DEFINITIVE TREATMENT DISCONTINUATION 
Does not apply. 
 
11. STATISTICAL CONSIDERATIONS 
11.1 Determination of sample size 
 The PaCO2 in the treatment group is expected to be arounf 45 mmHg, due to the study design.  A clinically 
significant hypoventilation is indicated by a PaCO2 around 50 mmHg and could be expected in the control 
group. We aim at observing such a 5 mmHg PaCO2 difference between groups with power 90% and 
alpha=0.05.  PaCO2 SD during sedation is considered around 5 mmHg (Yamakage M, Kamada Y,   Toriyabe 
M, Honma Y, Namiki A. Changes in respiratory pattern and arterial blood gases during sedation with 
propofol or midazolam in spinal anesthesia.  J Clin Anesth 1999; 11:375–9). 
This yields a calculated 44 patients (22 per group). 
We decide to enroll 60 patients (30 per group) taking into account dropouts and possible non-normality. 
 
11.2 Statistical Methods  
All data will be analyzed according to the intention-to-treat principle, beginning immediately after 
randomization. Data will be stored electronically and analyzed by use of the R software ( R Development 
Core Team (2008). R: A language and environment for  statistical computing. R Foundation for Statistical 
Computing,  Vienna, Austria. ISBN 3-900051-07-0, URL http://www.R-project.org.).  
All data analysis will be carried out according to a pre-established analysis plan. 

Seomask 
version n° 1  
 
 
 
December 28th, 2017 
 
 
10
Continuous data will be reported as mean±SD[median(IQR)] and compared with the Student t tests on the 
equality of means or with the Wilcoxon rank-sum test (Mann-Whitney  two-sample statistic) if not normal. 
Normality will be tested by visual inspection and with the Shapiro-Wilk W test for normality. 
Categorical data will be reported as number(percentage) and compared with the Pearson's chi-squared test 
Fisher's exact test if appropriate. 
 
11.3 Interim analysis 
Not needed. 
 
12. ETHICAL AND REGULATORY CONSIDERATIONS 
This clinical trial will be conducted in accordance with the Helsinki declaration, all applicable amendments 
and the guidelines for Good Clinical Practice.  This clinical trial will be conducted in compliance with all 
international laws and regulations, and national laws and regulations of the country in which the clinical 
trial is performed, as well as any applicable guidelines. 
12.1 Informed Consent  
The investigator, or a trained colleague will fully inform the patient about all the aspects of the clinical trial, 
in language and terms the subject is able to understand. Patients will be informed about the possibility to 
withdraw from the study. Written informed consent will be obtain and it will be stored together with 
Investigator’s file. A copy of the consent will be given to the patient. 
12.2 Independent Ethics Committee Approval (IRB/IEC)  
This clinical trial protocol as well as the Informed Consent have been submitted to the Ethics Committee. 
12.3 Responsibilities of the investigator(s)  
The investigator undertakes to perform the clinical trial in accordance with this clinical trial protocol, ICH 
/Good Clinical Practice and the applicable regulatory requirements.  
The investigator will provide any missing information requested in the Case Report Form (CRF). 
12.4 Responsibilities of the sponsor/promoter 
Does not apply. 
 
13.  DATA MANAGEMENT  
13.1 Source Documents 
According to the ICH /Good Clinical Practice, the monitoring team must check the Case Report Form entries 
against the source documents. 
13.2 Case Report Forms (CRFs) 
It is the responsibility of the investigator to maintain adequate and accurate web based CRFs (a printed 
copy is attached to this application). All CRFs will be completed electronically in their entirety to ensure 
accurate interpretation of data.  
 
14. DATA PROTECTION 
Data will be stored in electronic database without indicating the name of the patients (a numeric code will 
be used). 
The promoter (OSR) has the ownership of the data, in particular stored and secured by the Department of 
Anesthesia. 
15. CLINICAL TRIAL RESULTS 
The Promoter will be responsible for preparing a Clinical Study Report.  
When the data from all investigational sites have been fully analyzed, the results of the clinical trial will be 
communicated to all the investigators and to Competent Authority. 
 
16. BIBLIOGRAPHIC REFERENCES  
1. Yamakage M,  Kamada Y, Toriyabe M, et al. Changes in respiratory pattern and arterial blood gases 
during sedation with propofol or midazolam in spinal anesthesia.  J Clin Anesth 1999; 11:375–9 
 

Seomask 
version n° 1  
 
 
 
December 28th, 2017 
 
 
11
2. Thompson A. M., Wright D. J., Murray W., et al. Analysis of 153 deaths after upper gastrointestinal 
endoscopy:room for improvement? Surg endosc 2004; 18: 22–25 
 
3. Daşkaya H., Uysal H., Çiftçi T. et al, Use of the gastro-laryngeal tube in endoscopic retrograde 
cholangiopancreatography cases under sedation/analgesia. Turk J Gastroenterol 2016; 27: 246-51 
 
4.Cong Y., Sun X., Mask adaptor-a novel method of positive pressure ventilation during propofol deep 
sedation for upper GI endoscopy. Gastrointestinal Endoscopy 2008; 68: 127-31