Clinical trial NCT03829618
Conditions: Bronchiectasis Adult Mediastinal Lymphadenopathy Pneumonia Chest--Diseases Infiltrates Bronchopulmonary Disease Cancer, Lung
Sponsor: Milton S. Hershey Medical Center
Start date: 2019-04-01; Completion date: 2020-08-31
Enrollment: 29 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to assess if there is decrease in cough during flexible bronchoscopy and endobronchial ultrasound when different modes of lidocaine administration are used. The modes of administration being evaluated are topical, nebulized and atomized.

Detailed description:

Arms: arm 1: 16 ml of 1% lidocaine sprayed in 4 ml aliquots to vocal cords, midtrachea, left main stem bronchus and right main stem bronchus. arm 2: 2% lidocaine dosed at 2mg/kg with max dose of 160mg nebulized via jet nebulizer in operating room over ten minutes. arm 3: 2% lidocaine dosed at 2mg/kg with max dose of 160mg nebulized via vibrating mesh nebulizer in operating room over ten minutes.
Interventions: intervention 1: Topical lidocaine intervention 2: Nebuliser solution intervention 3: Nebuliser Suspension
Intervention descriptions: intervention 1: 1% lidocaine topically applied in 4 mL aliquots intervention 2: 2% lidocaine dose at 2 mg/kg (max 160 mg) applied via jet nebulizer intervention 3: 2% lidocaine dosed at 2 mg/kg (max 160 mg) applied via vibrating mesh nebulizer

Protocol documents:
Prot_SAP_000.pdf: 
Page 1 of 18 (V.04/27/2017)
HRP-592 - Protocol for Human Subject 
Research with Use of Test Article(s)
Protocol Title:
Comparison of Lidocaine Administration during Flexible Bronchoscopy and Endobronchial Ultrasound: Topical vs 
Nebulized vs Atomized.
Principal Investigator:
Name: Jennifer W. Toth, MD
Department: Pulmonary, Allergy and Critical Care, Division of Interventional Pulmonary
Telephone: 717.531.6757
E-mail Address: jtoth@pennstatehealth.psu.edu
Version Date:
December 18th, 2018
Clinicaltrials.gov Registration #:
Important Instructions for Using This Protocol Template:
1.
Add this completed protocol template to your study in CATS IRB (http://irb.psu.edu) on the “Basic Information” 
page, item 7. 
2.
This template is provided to help investigators prepare a protocol that includes the necessary information needed 
by the IRB to determine whether a study meets all applicable criteria for approval. 
3.
Type your protocol responses below the gray instructional boxes of guidance language.  If the section or item is 
not applicable, indicate not applicable.
4.
For research being conducted at Penn State Hershey or by Penn State Hershey researchers only, delete the 
instructional boxes from the final version of the protocol prior to upload to CATS IRB (http://irb.psu.edu).  For all 
other research, do not delete the instructional boxes from the final version of the protocol.
5.
When making revisions to this protocol as requested by the IRB, please follow the instructions outlined in the Study 
Submission Guide available in the Help Center in CATS IRB (http://irb.psu.edu) for using track changes. 
If you need help…
University Park and other campuses:
Office for Research Protections Human Research Protection Program
The 330 Building, Suite 205
University Park, PA 16802-7014
Phone: 814-865-1775
Fax: 814-863-8699
Email: irb-orp@psu.edu
College of Medicine and Hershey Medical Center:
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Hershey, PA 17033
(Physical Office Location: Academic Support Building Room 1140)
Phone: 717-531-5687
Fax number: 717-531-3937
Email: irb-hspo@psu.edu
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Table of Contents
1.
Objectives
2.
Background
3.
Inclusion and Exclusion Criteria
4.
Recruitment Methods
5.
Consent Process and Documentation
6.
HIPAA Research Authorization and/or Waiver or Alteration of Authorization
7.
Study Design and Procedures
8.
Subject Numbers and Statistical Plan
9.
Confidentiality, Privacy and Data Management 
10.
Data and Safety Monitoring Plan
11.
Risks
12.
Potential Benefits to Subjects and Others
13.
Sharing Results with Subjects
14.
Subject Stipend (Compensation) and/or Travel Reimbursements
15.
Economic Burden to Subjects
16.
Resources Available
17.
Other Approvals
18.
Multi-Site Research
19.
Adverse Event Reporting
20.
Study Monitoring, Auditing and Inspecting
21.
Future Undetermined Research: Data and Specimen Banking
22.
References
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1.
Objectives
1.1.
Study Objectives
The purpose of this feasibility study is to use a multimodal approach of general anesthesia 
supplemented by topical analgesia during flexible bronchoscopy and endobronchial ultrasound.  The aim 
is to determine if the administration of lidocaine via “spray as you go” vs. nebulizer would result in 
reduced severity of cough during the procedure and maximizing efficient sample acquisition while 
limiting the amount of general anesthetic given. The use of the vibrating mesh nebulizer is presumed to 
lead to an even distribution during lidocaine administration and thereby lead to decreased number of 
severe coughs during procedure improving efficiency of sample acquisition and reduce the dose of 
general anesthetic required.
1.2.
Primary Study Endpoints
The primary endpoint will assess if different modes of lidocaine administration (“spray as you go” vs 
nebulized vs atomized) decrease the severity of intraoperative coughing.  Severe coughs will be 
identified by the anesthesiologist and bronchoscopist as cough which results in pausing procedure 
and/or requiring repeated dosing of anesthetic.
1.3.
Secondary Study Endpoints
Secondary endpoints will include: additional amount(s) of fentanyl and propofol used to suppress cough 
during procedure, cough and sore throat post-procedure and time to emergence following the end of 
the procedure.
2.
Background
2.1.
Scientific Background and Gaps
Flexible bronchoscopy and endobronchial ultrasound with transbronchial needle aspiration are the 
most commonly performed procedures by a pulmonologist when assessing lung disease, mediastinal 
and hilar lymphadenopathy.  A combination of general anesthesia along with topical analgesia is 
important to maximize patient tolerance while limiting cough.  The use of lidocaine as a topical 
anesthetic has the benefit of reducing the overall depth of the anesthetic with minimal risk of 
complications related to systemic absorption. 
The current consensus statement on analgesia, anesthesia and sedation during bronchoscopy (Chest 
2005) recommend sedation with Propofol which allows for shorter patient recovery, analgesia with 
Fentanyl due to its quick onset of action, rapid peak effect and relatively short duration of effect as well 
as topical anesthesia using lidocaine to provide the optimal environment for bronchoscopy while also 
limiting potential risks.  Currently however, the optimal mode of administration of topical lidocaine has 
yet to be determined.
2.2.
Previous Data
A previous study by Dreher, M., et al. published in Respiration evaluated nebulized versus “spray as you 
go” application of lidocaine during flexible bronchoscopy.   This study selected patients undergoing 
diagnostic bronchoscopy with endobronchial or transbronchial biopsy.  All patients underwent general 
anesthesia and intubation prior to procedure, then were randomized to a topical lidocaine versus Enk 
Fiberoptic Atomizer Set.  Primary outcomes were the Aldrete score >9 to assess recovery after 
bronchoscopy and patient perceived tolerance with the visual analogue scale.  This study showed no 
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difference between the two groups, however the primary outcome was patient comfort during 
procedure and most patients had complete amnesia for the procedure.  Bronchoscopist and 
anesthesiologist evaluation of cough during procedure was not evaluated.
Another study by Stolz D., et al. published in Chest was a prospective, randomized, placebo controlled 
double blind trial which evaluated whether nebulized lidocaine provides additional benefit and reduces 
total anesthetic dose required during bronchoscopy in addition to topical lidocaine administration. 
Primary outcomes including both patient and operator visual analogue score for cough which were 
similar between groups. This however was not a comparison trial between different administration 
techniques of the lidocaine and included only flexible bronchoscopy patients, endobronchial ultrasound 
and biopsy patients were not included.
2.3.
Study Rationale
While the procedures of flexible bronchoscopy and endobronchial ultrasound is commonly performed to 
assess a wide range of lung disease, studies evaluating the mode of administration of topical lidocaine to 
prevent coughing and improve efficiency of the procedure have not yet been completed.  We propose a 
prospective, randomized, stratified sampling, open label study of topical vs nebulized vs atomized 
lidocaine during flexible bronchoscopy and endobronchial ultrasound.   Postoperative outcome 
assessors will be blinded to intraoperative therapy.  We propose to evaluate the different modes of 
administration of topical lidocaine and their effect on the number of severe coughs as per anesthesia 
and the bronchoscopist, total dosing of anesthesia, post-procedure cough and sore throat and 
complications related to lidocaine.
As there have been no studies in regards to the mode of lidocaine application in bronchoscopy, our 
study is a feasability study to identify if a difference is present between nebulized and topical groups.  If 
one is identified, we will plan to determine number needed to power a future superiority study.
3.
Inclusion and Exclusion Criteria
3.1.
Inclusion Criteria
The following inclusion criteria will be used:
1.
Diagnosis of mediastinal and/or hilar lymphadenopathy requiring endobronchial ultrasound 
evaluation and transbronchial needle aspiration.
2.
Diagnosis of pulmonary disease requiring flexible bronchoscopy
3.
Greater than 18 years of age. 
Vulnerable populations as identified in HRP-412, HRP-413, HRP-414, HRP-415, HRP-416 and HRP-417 will 
not be included in this study.
3.2.
Exclusion Criteria
The following exclusion criteria will be used:
1.
Any intervention beyond flexible bronchoscopy and EBUS/TBNA
2.
Inability to tolerate bronchoscopy.
3.
Patients that receive paralytics.
4.
Patients with neuromuscular diseases.
5.
Inability to consent for procedures.
6.
Allergies to lidocaine or any other drugs used in protocol.
7.
Existing renal insufficiency or liver disease
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3.3.
Early Withdrawal of Subjects
3.3.1.Criteria for removal from study
Withdrawn from the study if the bronchoscopy is terminated early due to patient safety 
concerns.  Withdrawn if the subject withdraws consent for the study or the procedure. Subjects 
will retain the right to withdrawal consent at any time without consequences of any kind, 
including the right to future treatment.  
There are no identified safety concerns, nor concerns of disease progression as this study will 
not interfere with diagnosis nor treatment.  Individuals enrolled in the study will continue to 
receive treatment consistent with accepted standard of care.  Based on study protocol 
diagnostic and outcome information will be obtained, but will not be used to alter medical 
decision making.
3.3.2.Follow-up for withdrawn subjects
Follow up by routine standard of care treatment.  The intervention of this study is limited and 
has no lasting effects therefore long term follow up is not required. 
Individuals that are withdrawn from the study will continue treatment and follow up visits 
consistent with standard of care.  Currently there is no anticipated need to replace individuals 
withdrawn from the study as there will be concurrent active recruitment.
4.
Recruitment Methods
4.1.
Identification of subjects
Identified from pool of patients who will already be undergoing with planned flexible bronchoscopy 
and/or endobronchial ultrasound by an interventional pulmonologist in the operating room setting.  
They will be identified by review of the operating room schedule and through the interventional 
pulmonology clinic.
4.2.
Recruitment process
Once potential subjects are identified from interventional pulmonology clinic or operating room 
schedule by the interventional pulmonology attending, patients will be evaluated and recommendations 
given prior to and independent of study enrollment.  Individuals that meet inclusion criteria during in 
person questioning will be referred to a study team member.  The team member will review the case 
and determine eligibility.  If eligible, the team member will review the study with the subject, and obtain 
consent.
4.3.
Recruitment materials
None.
4.4.
Eligibility/screening of subjects
Not applicable.
5.
Consent Process and Documentation
5.1.
Consent Process 
 
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5.1.1.Obtaining Informed Consent
5.1.1.1.Timing and Location of Consent
For outpatients, consent for this study will be obtained on Penn State Hershey 
Medical center premises, at the interventional pulmonology clinic.  Consent will 
be obtained immediately following a patient’s medical office visit, by an 
authorized study team member.  Consents will be obtained during normal clinic 
business hours.  During clinic hours, translation services and impartial witnesses 
are available. Family members typically attend clinic visits and will be 
encouraged to participate in the consent process.
For inpatients, consent for this study will be obtained in their designated 
hospital room the day before their scheduled procedure.  Consent will be 
obtained by an authorized study team member. Floor nurses as well as visiting 
family members will be available as impartial witnesses and will be encouraged 
to participate in the consent process.
For outpatients not previously seen in clinic, consent will be obtained in the pre-
operative care unit the day of the scheduled procedure. Consent will be 
obtained by an authorized study team member.  Family who are accompanying 
patient for procedure will be encouraged to participate in the consent process.
5.1.1.2.Coercion or Undue Influence during Consent
Consent will be obtained by the interventional pulmonologist who will be 
performing the procedure.  Nursing staff is readily available in the clinic, medical 
floor and preoperative area for witness of consent.  It will be explicitly stated 
that the care will not deviate from standard of care, and consent or abstention 
to this study will not affect the procedure they will receive, nor the level of 
medical care. If at any point the study subject expresses concern or 
unwillingness to proceed than the consent process will be terminated, not 
included in the study and explained that the same standard of care will be 
provided regardless. 
The current IRB approved consent form will be used.  Consent will be obtained 
following clinic visit in outpatient setting, after interventional pulmonology 
consult in inpatient setting and after procedure consent in pre-operative area, 
allowing detachment of the study and the medical care received. Patients are 
encouraged to have family members and other representatives present and will 
also be encouraged to stay for consent of the study.  Questions will be 
encouraged, and answered adequately.  Time will be given if the individual 
desires to discuss with family members or others. Voluntary enrollment will be 
explicitly stated.  There are many Penn State employees that will be available as 
impartial witnesses I all three settings.  Penn State translation services are 
available for non-English speaking individuals.  If at any point the individual 
communicates they do not want to take part in the study, the consent process 
will immediately terminate.    
5.1.2.Waiver or alteration of the informed consent requirement
Partial waiver will be obtained as per section 6.2 and 6.3.
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5.2.
Consent Documentation
5.2.1.Written Documentation of Consent
Written documentation of consent will be on the IRB approved consent form, and in an 
understandable language for the individual.  The individuals name will be printed on page 1 of 
the form, and the person or representative will print, sign and date the consent form.  The study 
team member obtaining consent will also print, sign and date, as well as the impartial witness.  
Finally a copy of the signed and dated consent will be given to the individual or representative 
and uploaded into the electronic medical record.  
5.2.2.Waiver of Documentation of Consent (Implied consent, Verbal consent, etc.)
Not applicable.
5.3.
Consent – Other Considerations 
5.3.1.Non-English Speaking Subjects
This study does not specifically target non-English speaking populations.  If non-English speaking 
individuals are encountered, current IRB approved non-English short forms will be used for 
Spanish, Vietnamese, Russian, Italian, and French.  The study team members obtaining consent 
will use English and translation performed to the desired language by the Penn State translation 
services.  
5.3.2.Cognitively Impaired Adults
5.3.2.1.Capability of Providing Consent
Capacity will be determined at time of consent for procedure.  If they do not have 
the capacity to consent for procedure, they will not be able to consent for the 
research study.
5.3.2.2.Adults Unable To Consent
Not applicable.
5.3.2.3.Assent of Adults Unable to Consent
Not applicable.
5.3.3.Subjects who are not yet adults (infants, children, teenagers) 
5.3.3.1.Parental Permission
Not applicable.
5.3.3.2.Assent of subjects who are not yet adults
Not applicable.
6.
HIPAA Research Authorization and/or Waiver or Alteration of Authorization
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6.1.
Authorization and/or Waiver or Alteration of Authorization for the Uses and Disclosures of PHI
Check all that apply:
 
Not applicable, no identifiable protected health information (PHI) is accessed, used or 
disclosed in this study. [Mark all parts of sections 6.2 and 6.3 as not applicable]
Authorization will be obtained and documented as part of the consent process. [If this is the 
only box checked, mark sections 6.2 and 6.3 as not applicable]
Partial waiver is requested for recruitment purposes only (Check this box if patients’ medical 
records will be accessed to determine eligibility before consent/authorization has been 
obtained). [Complete all parts of sections 6.2 and 6.3]
Full waiver is requested for entire research study (e.g., medical record review studies). 
[Complete all parts of sections 6.2 and 6.3]
Alteration is requested to waive requirement for written documentation of authorization 
(verbal authorization will be obtained). [Complete all parts of sections 6.2 and 6.3]
6.2.
Waiver or Alteration of Authorization for the Uses and Disclosures of PHI
6.2.1.Access, use or disclosure of PHI representing no more than a minimal risk to the privacy of the 
individual
6.2.1.1.Plan to protect PHI from improper use or disclosure
Information is included in the “Confidentiality, Privacy and Data Management” 
section of this protocol.
6.2.1.2.Plan to destroy identifiers or a justification for retaining identifiers 
Identifier will be retained through course of study as consent forms must be 
collected and stored.
6.2.2.Explanation for why the research could not practicably be conducted without access to and 
use of PHI
Information must be obtained from the subject’s electronic medical record during 
recruitment to determine eligibility and, in some cases, to confirm information 
discussed with the subject in regards to their medical history.
6.2.3.Explanation for why the research could not practicably be conducted without the waiver or 
alteration of authorization
The waiver is requested only for recruitment to determine subject eligibility to ensure 
that no medical conditions that fall into the exclusion criteria are present and would 
thus preclude enrollment. This waiver will minimize the enrollment of subjects’ who 
may ultimately fail to meet the study inclusion/exclusion criteria.
6.3.
Waiver or alteration of authorization statements of agreement
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Protected health information obtained as part of this research will not be reused or disclosed to any 
other person or entity, except as required by law, for authorized oversight of the research study, or for 
other permitted uses and disclosures according to federal regulations. 
The research team will collect only information essential to the study and in accord with the ‘Minimum 
Necessary’ standard (information reasonably necessary to accomplish the objectives of the research) 
per federal regulations. 
Access to the information will be limited, to the greatest extent possible, within the research team. All 
disclosures or releases of identifiable information granted under this waiver will be accounted for and 
documented.
7.
Study Design and Procedures
7.1.
Study Design
Patient is identified and consent is obtained in clinic, hospital room or pre-operative area.  In the Same 
Day Pre-Anesthesia Care Unit they will receive Robitussin DM 20 ml syrup orally (Dextromethorphan 
20mg) at least 60 minutes prior to bronchoscopy. 
Once in the main procedure room patients will be induced into an anesthetic state using the following 
medications and dosing ranges.  It will be titrated by anesthesiologist at bedside with goal to achieve 
hypnosis and apnea without profound bradycardia. The duration of the infusion is as required for the 
duration of the procedure. 
- Propofol (1-3 mg/kg bolus and infusion of 50-200 mcg/kg), fentanyl 25-50 mcg on induction and 
alfentanil as a continuous infusion will be given at a rate of 0.5-2 mcg/kg/min with 1-3 mcg/kg bolus 
every 2-5min if need for further cough suppression. The Propofol infusion will be titrated to maintain BIS 
values between 40-60 for the duration of the procedure. When it is anticipated that the procedure will 
conclude within the next 10 minutes, the Propofol and alfentanil infusions will be stopped.  
 Contingency Plan:  If despite the maximum dose of Propofol (150 mcg/kg/min) and alfentanil the 
patient continues to cough such that the procedure cannot be carried out, then Rocuronium will be 
administered IV (dose 20-40 mg at the discretion of the anesthesiologist) and its residual effect will be 
reversed using neostigmine (20-70 mcg/kg) and glycopyrrolate (10 mcg/kg) at the end of the procedure.
The patient’s airway will be managed using a laryngeal mask airway (LMA) (Ambu Aura-I Size 4 or 5).  
Their airways will be anesthetized using a maximum of 2 mg per kg (max dose 160mg) of lidocaine, 
administered by one of the following techniques below. Randomization will be completed by selection 
of unmarked envelope.
1. “Spray as you go” - 16mL of 1% lidocaine sprayed in 4 mL aliquots. One at the vocal cords, 
one at midtrachea, one at left main stem bronchus and one at right mainstream bronchus.
2. Nebulizer – 2 % (preservative free) lidocaine (dose 2mg/kg max dose 160 mg) will be 
administered via a jet nebulizer, in the operating room over ten minutes, followed by 
procedure immediately after. The patient will be sitting propped up and his SpO2, EKG and 
BP will be monitored during this time. The jet nebulizer supply tube will be connected to 
central oxygen at 6 L/min and the duration of nebulization will be dryness of the nebulizing 
chamber or max of 10 minutes.  [The Salter Series Small Volume Jet Nebulizer will be used.]
3. Vibrating Mesh Nebulizer –  2 % (preservative free) lidocaine (dose 2mg/kg max dose 160 
mg) will be administered via a vibrating mesh nebulizer, in the operating room over ten 
minutes, followed by procedure immediately after. The patient will be sitting propped up 
and his SpO2, EKG and BP will be monitored during this time. The jet nebulizer will be 
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connected to central oxygen at 6 L/min and the duration of nebulization will be dryness of 
the nebulizing chamber or max of 10 minutes. [The Aerogen Solo Vibrating Mesh Nebulizer 
will be used.]
Patient will undergo scheduled procedure of flexible bronchoscopy or endobronchial ultrasound 
examination.  During procedure, bronchoscopist and anesthesiologist will count the number of episodes 
of cough.  Cough is defined as a cough which requires intervention such as additional dose of anesthetic 
or requires a pause in the procedure.  During procedure, BIS monitor average, number of vasopressor 
interventions for MAP <60, induction time, procedure time and wake up time will be documented in the 
research record.
Following procedure, patient will be brought to post-op anesthesia care unit.  Time to discharge 
readiness will be collected as well as the responses of the patient to the following questions:
- sore throat: absent, mild, moderate, severe
- cough: absent, mild, moderate, severe
7.2.
Study Procedures
7.2.1.Visit 1
Study procedure is completed over the course of one day as described above in study design.
7.3.
Duration of Participation
Duration is time from consent signing until patient is medically ready for discharge.
7.4.
Test Article(s) (Study Drug(s) and/or Study Device(s))
7.4.1.Description
160mg of 1% lidocaine is approved by the FDA for anesthetizing tracheobronchial tree.  The 
mode of administration (spray as you go vs nebulized vs atomized) has been shown to have 
similar safety profile however efficacy has not been determined.
7.4.2.Treatment Regimen
Their airways will be anesthetized using 160mg of lidocaine, administered by one of the following 
techniques:
1. “Spray as you go” - 16mL of 1% lidocaine sprayed in 4 mL aliquots. One at the vocal cords, 
one at midtrachea, one at left main stem bronchus and one at right mainstream bronchus.
2. Jet Nebulizer – 8 mL of 2 % lidocaine administered via a jet nebulizer over ten minutes, 
followed by procedure immediately after.
3. Vibrating Mesh Nebulizer – 8 mL of 2 % lidocaine administered via a vibrating mesh 
nebulizer over ten minutes, followed by procedure immediately after.
7.4.3.Method for Assigning Subject to Treatment Groups
Subject forms will have administration mode documented and will be placed in sealed 
envelopes.  Immediately prior to procedure, envelope will be opened to determine which mode 
of lidocaine administration will be performed. Lauren Ventola will secure all envelopes within 
locked cabinet in Jennifer Toth’s office.  Subject will be told of their assigned treatment group.  
Inpatient/Outpatient will be a 50/50% stratification.
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7.4.4.Subject Compliance Monitoring
Not required to be monitored as medication is administered by the anesthesiologist or 
bronchoscopist prior to or during the procedure
7.4.5.Blinding of the Test Article
Mode of administration will not be blinded to anesthesiologist or bronchoscopist.
7.4.6.Receiving, Storage, Dispensing and Return 
7.4.6.1.Receipt of Test Article 
Lidocaine will be ordered from the pharmacy. The vibrating mesh nebulizer and 
jet nebulizer will be set up by anesthesiologist and spray as you go will be set up 
by OR staff and bronchoscopist.
7.4.6.2.Storage
Same medication obtained from pharmacy is used across all three groups, the 
mode of administration is only part changed and will be completed by 
anesthesiologist and/or bronchoscopist.
7.4.6.3.Preparation and Dispensing
Mode of administration will be determined day of procedure by selection of 
randomized, sealed envelopes containing subject form with administration 
mode.  The atomized and nebulized lidocaine will be prepared and administered 
by the anesthesiologist.  The “spray as you go” lidocaine will be prepared by the 
scrub nurse and administered by the bronchoscopist.  Preparation involves 
loading medication into administration devices.
Medication will not be dispensed directly to subject.
7.4.6.4.Return or Destruction of the Test Article
Not applicable.
7.4.6.5. Prior and Concomitant Therapy
Dextromethorphan syrup 90mg will be given 60 minutes prior to procedure. 
Post-procedure, subject will be able to use nebulized albuterol. No medications 
are contraindicated.
8.
Subject Numbers and Statistical Plan
8.1.
Number of Subjects
48 patients randomly assigned to lidocaine application technique (24 in topical, 12 in jet nebulizer and 
12 in vibrating mesh nebulizer). Among each group there will be stratification of flexible 
bronchoscopy/endobronchial ultrasound procedures and inpatient/outpatient.
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8.2.
Sample size determination
Not applicable.
8.3.
Statistical methods
Descriptive statistics will be used for continuous variables, and presented as medians and interquartile 
ranges.  Categorical variables will be expressed as percentages.  The estimated sample size within our 
institution is 48 patients.
9.
Confidentiality, Privacy and Data Management 
See Research Data Plan Review Form.
10.
Data and Safety Monitoring Plan
10.1. Periodic evaluation of data
Data will be evaluated half way through and at completion of study by primary investigator
10.2. Data that are reviewed
Data collected on subject forms with comparison to Red Cap data. 
10.3. Method of collection of safety information
Safety data will be collected at the time of the procedure by the primary investigator.
10.4. Frequency of data collection
With each procedure and data collection.
10.5. Individuals reviewing the data
The primary investigator as well as study team members.
10.6. Frequency of review of cumulative data
Half way through bronchoscopy data collection and at completion.  Safety data will be collected during 
each procedure. 
10.7. Statistical tests
Descriptive statistics will be used for continuous variables, and presented as medians and interquartile 
ranges.  Categorical variables will be expressed as percentages.  
10.8. Suspension of research
Will be based on safety data collection following each subject’s bronchoscopy.
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11.
Risks
There is the potential risk of loss of confidentiality with this study due to consent being required however no 
personal identifiers will be attached to the data we collect.  There is no other forseeable risk to the patients 
involved in this study.  All medications and procedures fall within standard treatment and standard of care.  The 
only variable will be the delivery method of the medication used during bronchoscopy.  There is no risk to the 
researchers or hospital staff either.  Loss of confidentiality is always a potential risk, but no protected health 
information will be maintained or collected, minimizing this risk. Risk of randomization is also present however 
all modalities are considered standard of care. 
12.
Potential Benefits to Subjects and Others
12.1. Potential Benefits to Subjects
No direct benefit to subjects.
12.2. Potential Benefits to Others
Benefit to society by determining what mode of application of lidocaine prevents severe cough and 
improves efficiency and decreases potential risks during flexible bronchoscopy and endobronchial 
ultrasound.
13.
Sharing Results with Subjects
Not applicable.
14.
Subject Stipend (Compensation) and/or Travel Reimbursements
Not applicable.
15.
Economic Burden to Subjects
15.1. Costs 
Not applicable.
15.2. Compensation for research-related injury
Not applicable.
16.
Resources Available
16.1. Facilities and locations
Pre-anesthesia care unit, floor room or interventional pulmonology clinic where consent process will 
take place.
Pre-anesthesia care unit where patient will receive dextromethorphan.
Main Procedure Room 1 where lidocaine will be administered and procedure completed. Will collect 
number of severe coughs, amount of anesthesia, time of procedure and wake up time.
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Post-anesthesia care unit where time to discharge readiness, patient cough severity and sore throat 
severity will be collected.
16.2. Feasibility of recruiting the required number of subjects
There are over 600 combined flexible bronchoscopies performed per year, and include a combination of 
basic bronchoscopy and EBUS.  
16.3. PI Time devoted to conducting the research
The PI will be responsible for oversight of recruitment, oversight of data entry accuracy, and primary 
data analysis. The PI will also have initial overview to ensure subject safety.  
16.4. Availability of medical or psychological resources
Not applicable.
16.5. Process for informing Study Team
The research team currently consists of the principal investigator and four co-investigators.  If additional 
members are added, they will be educated on the confidentiality and data management principles 
outlined in section 9.
17.
Other Approvals
17.1. Other Approvals from External Entities
Not applicable.
17.2. Internal PSU Committee Approvals
Check all that apply:
  Anatomic Pathology – Hershey only – Research involves the collection of tissues or use of pathologic 
specimens. Upload a copy of HRP-902 - Human Tissue For Research Form on the “Supporting 
Documents” page in CATS IRB. This form is available in the CATS IRB Library.
  Animal Care and Use – All campuses – Human research involves animals and humans or the use of 
human tissues in animals
  Biosafety – All campuses – Research involves biohazardous materials (human biological specimens 
in a PSU research lab, biological toxins, carcinogens, infectious agents, recombinant viruses or DNA or 
gene therapy). 
  Clinical Laboratories – Hershey only – Collection, processing and/or storage of extra tubes of body 
fluid specimens for research purposes by the Clinical Laboratories; and/or use of body fluids that had 
been collected for clinical purposes, but are no longer needed for clinical use. Upload a copy of HRP-901 
- Human Body Fluids for Research Form on the “Supporting Documents” page in CATS IRB. This form 
is available in the CATS IRB Library.
  Clinical Research Center (CRC) Advisory Committee– All campuses – Research involves the use of 
CRC services in any way.  
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  Conflict of Interest Review – All campuses – Research has one or more of study team members 
indicated as having a financial interest.
  Radiation Safety – Hershey only – Research involves research-related radiation procedures. All 
research involving radiation procedures (standard of care and/or research-related) must upload a copy 
of HRP-903 - Radiation Review Form on the “Supporting Documents” page in CATS IRB. This form is 
available in the CATS IRB Library.
  IND/IDE Audit – All campuses – Research in which the PSU researcher holds the IND or IDE or 
intends to hold the IND or IDE.
  Scientific Review – Hershey only – All investigator-written research studies requiring review by the 
convened IRB must provide documentation of scientific review with the IRB submission. The scientific 
review requirement may be fulfilled by one of the following: (1) external peer-review process; (2) 
department/institute scientific review committee; or (3) scientific review by the Clinical Research Center 
Advisory committee.  NOTE: Review by the Penn State Hershey Cancer Institute Scientific Review 
Committee is required if the study involves cancer prevention studies or cancer patients, records and/or 
tissues. For more information about this requirement see the IRB website at: 
http://www.pennstatehershey.org/web/irb/home/resources/investigator 
18.
Multi-Site Research
18.1. Communication Plans
Not applicable.
18.2. Data Submission and Security Plan
Not applicable.
18.3. Subject Enrollment
Not applicable.
18.4. Reporting of Adverse Events and New Information
Not applicable.
18.5. Audit and Monitoring Plans
Not applicable.
19.
Adverse Event Reporting
19.1. Adverse Event Definitions
For drug studies, incorporate the following definitions into the below responses, as written:
Adverse event
Any untoward medical occurrence associated with the use of the drug in humans, 
whether or not considered drug related
Adverse reaction
Any adverse event caused by a drug
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Suspected adverse 
reaction
Any adverse event for which there is a reasonable possibility that the drug caused 
the adverse event.  Suspected adverse reaction implies a lesser degree of 
certainty about causality than “adverse reaction”.

Reasonable possibility.  For the purpose of IND safety reporting, 
“reasonable possibility” means there is evidence to suggest a causal 
relationship between the drug and the adverse event.
Serious adverse 
event or Serious 
suspected adverse 
reaction
Serious adverse event or Serious suspected adverse reaction: An adverse event or 
suspected adverse reaction that in the view of either the investigator or sponsor, 
it results in any of the following outcomes: Death, a life-threatening adverse 
event, inpatient hospitalization or prolongation of existing hospitalization, a 
persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions, or a congenital anomaly/birth defect. Important 
medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the patient or subject and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition. 
Life-threatening 
adverse event or 
life-threatening 
suspected adverse 
reaction
An adverse event or suspected adverse reaction is considered “life-threatening” 
if, in the view of either the Investigator (i.e., the study site principal investigator) 
or Sponsor, its occurrence places the patient or research subject at immediate 
risk of death.  It does not include an adverse event or suspected adverse reaction 
that had it occurred in a more severe form, might have caused death.
Unexpected 
adverse event or 
Unexpected 
suspected adverse 
reaction.  
An adverse event or suspected adverse reaction is considered “unexpected” if it 
is not listed in the investigator brochure, general investigational plan, clinical 
protocol, or elsewhere in the current IND application; or is not listed at the 
specificity or severity that has been previously observed and/or specified.
19.2. Recording of Adverse Events
In accordance with applicable policies of The Pennsylvania State University Institutional Review Board 
(IRB), the investigator will report, to the IRB, any observed or reported harm (adverse event) 
experienced by a subject or other individual, which in the opinion of the investigator is determined to be 
(1) unexpected; and (2) probably related to the research procedures. Harms (adverse events) will be 
submitted to the IRB in accordance with the IRB policies and procedures.
19.3. Causality and Severity Assessments
The investigator will promptly review documented adverse events and abnormal test findings to 
determine 1) if the abnormal test finding should be classified as an adverse event; 2) if there is a 
reasonable possibility that the adverse event was caused by the study drug(s) or device(s); and 3) if the 
adverse event meets the criteria for a serious adverse event.
If the investigator’s final determination of causality is “unknown and of questionable relationship to the 
study drug(s) or device(s)”, the adverse event will be classified as associated with the use of the study 
drug(s) or device(s) for reporting purposes.  If the investigator’s final determination of causality is 
“unknown but not related to the study drug(s) or device(s)”, this determination and the rationale for the 
determination will be documented in the respective subject’s case history.
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19.4. Reporting of Adverse Reactions and Unanticipated Problems to the FDA  
19.4.1.
Written IND/IDE Safety Reports
Not applicable as new drug is not being studied, only comparison of mode of application.
19.4.2.
Telephoned IND Safety Reports – Fatal or Life-threatening Suspected Adverse 
Reactions
Not applicable as new drug is not being studied, only comparison of mode of application
19.5. Reporting Adverse Reactions and Unanticipated Problems to the Responsible IRB
In accordance with applicable policies of The Pennsylvania State University Institutional Review Board 
(IRB), the investigator will report, to the IRB, any observed or reported harm (adverse event) 
experienced by a subject or other individual, which in the opinion of the investigator is determined to be 
(1) unexpected; and (2) probably related to the research procedures. Harms (adverse events) will be 
submitted to the IRB in accordance with the IRB policies and procedures.
19.6. Unblinding Procedures
Modes of administration are not blinded.
19.7. Stopping Rules
Not applicable. 
20.
Study Monitoring, Auditing and Inspecting
20.1. Study Monitoring Plan
20.1.1.Quality Assurance and Quality Control
The principal investigator will be monitoring the conduct of the study throughout, data will be 
reviewed at 50% recruitment and 100% recruitment. 
20.1.2.Safety Monitoring
Adverse events will be identified and recorded on each subject form by the monitor and will be 
reviewed by the primary investigator who is present during all procedures.
 The Principal Investigator will confirm that all adverse events (AE) are correctly entered into 
the AE case report forms by the coordinator; be available to answer any questions that the 
coordinators may have concerning AEs; and will notify the IRB and/or DSMB of all applicable AEs 
as appropriate. All assessments of AEs will be made by a licensed medical professional who is an 
investigator on the research.
21.
Future Undetermined Research: Data and Specimen Banking
21.1. Data and/or specimens being stored
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Not Applicable. No specimens will be collected, and data will not be stored once this study is completed.
21.2. Location of storage
Not applicable
21.3. Duration of storage
Not applicable
21.4. Access to data and/or specimens
Not applicable
21.5. Procedures to release data or specimens
Not applicable
21.6. Process for returning results
Not applicable
22.
References
S Amini, S Peiman et al. The Effect of Dextromethorphan Premedication on Cough and Patient Tolerance During 
Flexible Bronchoscopy. J Bronchol Intervent Pulmonol 2017; 24: 263-267.
K Madan, S Biswal et al. 1% versus 2% Lignocaine for airway anesthesia in flexible bronchoscopy without 
lignocaine nebulization (LIFE). J Bronchol Intervent Pulmonol 2018; 00:000-000.
D Stolz, P C Hajed et al. Nebulized Lidocaine for Flexible Bronchoscopy. Chest 2005; 128; 1756-1760.
M Wahidi, et al. American College of Chest Physicians Consensus Statement on the Use of Topical Anesthesia, 
Analgesia and Sedation during Flexible Bronchoscopy in Adult patients. Chest 2011; 140 (5): 1342 – 1350
M Dreher, C Cornelissen, et al. Nebulized versus Standard Local Application of Lidocaine during Flexible 
Bronchoscopy: A Randomized Controlled Trial
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