Evaluation of 19-gauge vs 21-gauge EBUS TBNA in Assessing Thoracic Lymphadenopathy
Phase: NA
Conditions: Enlarged Lymph Nodes (Excluding Infective)
Sponsor: HealthPartners Institute

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Study Title: Evaluation of 19-gauge vs 21-
gauge EBUS TBNA in assessing thoracic 
lymphadenopathy  
 
NCT # NCT03657849 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Participant Contact Narrative: Evaluation of 19-gauge vs 21-gauge EBUS TBNA in assessing thoracic 
lymphadenopathy  
1. Summary: 
Endobronchial ultrasound-guided transbronchial needle aspirate (EBUS-TBNA) is a technique used to 
take samples of body tissue inside the chest without having to undergo an operation. 
During this procedure, a special telescope (called a bronchoscope) is inserted through the mouth into 
the airways. Ultrasound technology allows the doctor to see the structures just outside the airway. By 
being able to see the structures outside the airway, the doctor is able to safely pass a fine needle 
through the airway to take samples of abnormal tissue. 
 
EBUS-TBNA is used to take samples of tissue from the mediastinum. The mediastinum is the part of the 
chest between the lungs, and contains the heart, gullet, windpipe and lymph nodes. This area of the 
body is usually difficult to access without open surgery, hence the use of EBUS-TBNA. EBUS-TBNA may 
be used to investigate enlarged lymph nodes. This may be due to tuberculosis, sarcoidosis or cancer. 
 
Currently, smaller 21-gauge and larger 19-gauge needles are used during the EBUS-TBNA procedure at 
Regions Hospital. The purpose of this study is to find out which needle is better in finding the 
explanation for the enlarged lymph nodes, minimizing complications and any follow up procedures that 
may be necessary if we are unable to get enough tissue during the EBUS-TBNA procedure (surgical 
sampling, radiological sampling, and/or follow-up imaging).  
2. Study Aims: 
Using the larger 19-gauge needle instead of 21-gauge needle during EBUS TBNA will have higher yield 
without increasing complications 
Primary outcome: 
- 
19-gauge needle yield vs 21-gauge needle yield (true positive + true negative)/total) 
Secondary outcome: 
- 
Number of adequate samples by rapid onsite evaluation (ROSE) 
- 
cytology assessment of sample size 
- 
adequacy for molecular testing for lung cancer  
H1: 19-gauge needle will have at least 7% higher absolute yield than 21-gauge needle (current yield for 
21-g needle is 83%) 
3. Background, Rationale, Significance: 
Endobronchial ultrasound (EBUS) transbronchial needle aspiration (TBNA) is regarded as the preferred 
initial sampling method in assessment of mediastinal and hilar lymph adenopathy [1]. There are several 
needle sizes available commercially (25-, 22-, 21-, or 19-gauge). The size of the needle may affect the 

V3_29 Aug 2018 
quantity of tissue obtained, degree of tissue trauma, and amount of aspirated blood; each of which can 
affect the diagnostic yield. 
The 2016 CHEST guidelines [2], recommended the use of either 21- or 22-gauge needle during EBUS 
TBNA due to similar performance in the published literature but were unable to comment on other 
needle sizes due to lack of data. Since then few retrospective publications evaluated the recently 
available 19-gauge needle [3-8]. Biswas et al. repeated EBUS TBNA using 19-G needle in addition to 21-G 
needle for those patients with an initial negative 21-G EBUS TBNA but have high suspicion for 
sarcoidosis. The 19-G needle identified granulomas in all 11 patients compared to only 2 in the 21-G 
needle [4]. All these publications showed similar safety to smaller needles without increased bleeding 
risk.  
One of the drawbacks of EBUS TBNA is the loss of the histological structure due to smaller needle size, 
leading to lower yield in diagnoses that require preserving the cell structure to make the diagnosis, such 
as lymphomas (yield 68%) and sarcoidosis (yield 78%) compared to malignancy (yield 90%) [2, 9].  
When EBUS does not yield diagnosis, or doesn’t provide adequate tissue for molecular testing, patients 
are usually subjected to further diagnostic testing including repeat imaging studies, and commonly 
proceeding with more invasive procedures or surgical operations to obtain tissue, which in addition to 
delaying the diagnosis, causes significant distress for the patients and increase the cost.  
We believe that using 19-G needle during EBUS TBNA will improve the diagnostic yield overall and lead 
to more rapid diagnosis with fewer procedures for the patients which would improve patient’s 
satisfaction and decrease overall cost. The use of a 19-G needle could also result ultimately in fewer 
total passes which would typically result in less time under sedation for the patient. 
4. Approach: 
a. Study design:  
This is a prospective, diagnostic accuracy study. For each lymph node sampled, we will alternate 
between the 19-g and the 21-g with each pass. Typically, an average of 5 passes is done in each 
lymph node (though number ranges from 3-12 based on physician judgment), for the study a 
minimum of 3 passes with each needle will be requested to provide adequate tissue for comparison. 
The choice of needle for the first pass will be randomized. More passes will be allowed with 
alternating needles based clinicians’ judgment. Tissue obtained with the 19-g needles will be 
compared to tissue obtained with the 21-g needles with regards to diagnosis yield and adequacy for 
molecular testing. 
b. Population: 
i. 
Inclusion/Exclusion criteria 
Inclusion: 
- 
Age 18 years or older 
- 
Able to provide informed consent 
- 
Referred for EBUS TBNA sampling at Regions Hospital 
Exclusion:  
- 
On therapeutic warfarin, plavix or ticagrelor in the last 5 days 

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- 
INR >1.8, platelets <50K (evaluated at enrollment if patient has had them drawn as part 
of standard of care) 
ii. 
Sample size: 
A total of 50 patients will be enrolled, with an average of 1.7 lymphnodes sampled in each 
patient. Patients will be a convenience sample of patients referred to have the EBUS-TBNA 
procedure at Regions Hospital during the study period. 
c. Data collection process 
i. 
Process steps for identification of patients or records 
All patients referred for EBUS TBNA sampling at Regions Hospital who meet the 
inclusion/exclusion criteria will be approached to be enrolled. These patients will be 
identified by one of the study investigators. Of note, the exclusion criteria for INR and 
platelets will have been drawn and evaluated as part of standard of care only, based on 
the concern for coagulopathy. These are not required to be drawn for study enrollment. 
All physicians who perform this procedure at Regions Hospital are listed as investigators 
on this study. 
ii. 
Recruitment 
Subjects will be identified based on referral for EBUS TBNA procedure at Regions 
Hospital by one of the study investigators. Because all physicians who perform the EBUS 
TBNA procedure at Regions are study investigators, one of the investigators will be 
aware of every patient referred to have this procedure. Upon becoming aware of a 
patient referred for this procedure, the study investigator will discuss the procedure 
with the patient.  
iii. 
Consent 
After initial discussion of the procedure (standard of care), the investigator will describe 
the option to participate in the study as part of the procedure. The consent will be 
provided and reviewed with the patient/family, explaining the study verbally. The 
patient undergoing the procedure will provide consent for him- or herself and will be 
given sufficient time to privately review the consent form and discuss potential 
involvement in the study with any family members or LAR, as applicable. The 
investigator will again meet with the patient to address any questions and discuss 
enrollment. If appropriate, the investigator will obtain consent from the patient and 
begin the study procedures. 
iv. 
Data Sources: 
Data will be obtained before, during, and after the procedure. Demographic data will be 
obtained prior to the procedure via EMR. Number of passes with each size needle will 
be recorded in-person following each procedure. Diagnosis yield and adequacy for 
molecular testing will be obtained following the procedure, from the investigator 
performing the procedure and from pathology lab analysis as recorded in the EMR and 
communicated to the investigator per standard practice for this procedure. 
Complications will be assessed in-person during the procedure and following the 
procedure via review of the patient’s EMR 24+ hours after the procedure. 
d. Interventions, treatments 

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The EBUS-TBNA procedure is done with both 19-g and 21-g needles as standard of care. The 
conduct of the procedure with both needle sizes in a systematic manner with concurrent data 
collection as described above is specific to the study. This procedure is conducted at Regions 
Hospital by the listed study investigators. The procedure typically takes between 20 and 90 
minutes to complete, during which time the patient is under moderate sedation. During a 
standard procedure, the physician always performs at least four passes, sometimes more 
depending on the adequacy of the tissue being obtained. The average is 5.5 passes per lymph 
node. Participation in the study will likely result in an additional 1 to 2 total passes per patient. 
The randomization aspect of this study involves randomizing which needle size the physician 
starts with, with subsequent passes alternating between the two needle sizes. Initial needle size 
will be randomized using research randomizer. The randomization assignments for each study ID 
number will be kept in a document accessible by all investigators for use during enrollments. 
The investigators will not be blinded to the randomization assignment but the subjects will not 
be informed of which needle size they were assigned to start with. 
e. Outcome/endpoint and other variable definitions, and instruments used 
Variable Name 
Data Source 
Purpose 
Measurement Scale 
Ethnicity  
EMR 
Covariate 
Categorical 
Age and gender 
EMR 
Covariate 
Categorical 
BMI 
EMR 
Covariate 
Categorical 
Primary admission 
diagnosis  
EMR 
Covariate 
Categorical 
Secondary diagnoses 
EMR 
Covariate 
Categorical 
Passes with 21-g needle 
In-person CRF 
Covariate 
Continuous 
Passes with 19-g needle 
In-person CRF 
Covariate 
Continuous 
Total lymph nodes 
sampled 
In-person CRF 
Covariate 
Continuous 
Total sample yield 19-g 
In-person CRF 
Outcome 
Continuous 
Total sample yield 21-g 
In-person CRF 
Outcome 
Continuous 
Number of adequate 
samples by rapid onsite 
evaluation (ROSE) 
In-person CRF 
Outcome 
Continuous 

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Adequacy for molecular 
testing for lung cancer 
In-person CRF 
Outcome 
Binary 
Follow-up procedures 
required 
EMR 
Outcome 
Categorical 
Complications 
(hypotension, hypoxia, 
bleeding, other) 
In-person CRF/EMR 
Outcome 
Categorical 
Total time sedated for 
procedure 
In-person CRF/EMR 
Covariate 
Continuous 
 
f. Statistical analysis plan: 
 
As each needle will be used for every lymph node evaluated, we will assume a paired data 
structure for analytic strategies.  First, demographics and relevant patient factors in the study sample 
will be summarized using descriptive statistics.  Bivariate comparisons (by needle gauge) will be 
conducted using McNemar tests, paired t-tests, or alternatives appropriate for paired data as dictated 
by the nature of each variable.  If more flexibility is required (e.g., covariates for adjustment, specific 
correlation structure, random intercepts/slopes for patient clustering), we will specify linear mixed 
effects regression models to evaluate yield by needle gauge.  For secondary aims (complications, etc.) 
we will employ descriptive analyses – no formal hypotheses will be tested. 
 
g. Power analysis: 
 
Assuming 85 paired samples (50 patients * 1.7 lymph nodes), a one-sided α=0.05, and a 
standard deviation in yield of 10%, we expect 80% power to detect a mean difference of 2.7%.  Given 
our anticipated yields of 83% (21g) and 90% (19g; 7% increase), we expect sufficient power to detect a 
statistically significant difference in average yield by needle gauge. 
 
h. Strengths and Limitations: 
 
Strengths of the study include: 
- 
All physicians who perform the EBUS-TBNA procedure at Regions Hospital are investigators 
on this study, therefore we anticipate being able to approach all qualifying patients for 
enrollment. 
- 
Both needle sizes are currently used as standard of care, based on physician discretion. Use 
of these needles in the study is not far from the current standard of care and could inform a 
more standardized methodology for needle size in the future 
 
Limitations of the study include: 

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- 
Providers will not be blinded to needle gauge 
- 
Difficult to attribute complications to a single needle gauge, given both will be administered 
- 
As described above, procedural variation depends on physician judgment, which could bias 
results if judgment is differential with respect to needle gauge and/or yield 
 
5. Setting/Environment/Organizational feasibility 
This study will be conducted at Regions Hospital. Subjects will be identified by EBUS providers upon 
referral for the procedure. A letters of support from Dr. Kealy Ham, Department head of Critical 
Care Medicine at Regions Hospital, is included with this application. We do not anticipate that the 
use of both needle sizes during the procedure will significantly affect the resources or personnel 
utilized during these procedures.  
 
The Critical Care Research Center staff will be responsible for IRB correspondence and data 
management after collection. Study investigators are very involved with the study and have strong 
communication with the CCRC staff. The CCRC has conducted numerous studies in collaboration 
with the Regions Hospital Critical Care Medicine department. 
This study fits with the organizational goals at Regions Hospital because it may help to improve 
patient satisfaction, decrease patient time under anesthesia, and decrease cost of diagnosis for 
subjects being evaluated with the EBUS TBNA procedure.  
Investigator training: All investigators who will be performing the EBUS TBNA procedure are already 
trained in the conduct of the procedure and are already familiar with the use of both needle sizes. 
Prior to the start of the study data collection period, the investigators will attend a training meeting 
during which the specifics of the protocol will be reviewed and any questions discussed. A checklist 
will be made for use by the investigators during enrollments and investigators will be trained on this 
checklist and on the data collection instruments. Research staff will remain in close contact with the 
investigators and have a 24/7 research number where they can contact a research staff member.  
Investigators will notify CCRC research staff upon completion of enrollments and data collection for 
each patient. The research staff will collect all enrollment and data collection paperwork from the 
investigator. Data will be entered on a per-patient basis into an excel spreadsheet on the internal 
CCRC shared drive. Physical copies of patient study paperwork will be kept in a locked file cabinet in 
the CCRC, which is a limited access room that requires badge access with specific permission. 
6. Risks and Benefits 
Risks of EBUS-TBNA procedure 
The risks described in this section are related to the EBUS-TBNA procedure, whether done as 
standard of care or as part of this research study. Bronchoscopy is generally a safe procedure with 
about 1 in 100 patients reporting a complication. Complications related to the bronchoscopy 
procedure can be related to sedation for the procedure or directly from the bronchoscope. 
Complications related to sedation are hypoxia and hypotension, while those related to 
bronchoscopy are bronchospasm, laryngospasm, nausea, vomiting, bleeding due to scope trauma, 
abnormal heart rhythm, and fainting. Complications specifically related to EBUS-TBNA are collapse 
of the lung and bleeding.  

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An additional risk to subjects is the potential for a breach in patient confidentiality. All study 
personnel involved in data collection and analysis are trained in GCP, including issues of 
confidentiality. All study materials will be kept in a locked file cabinet in a badge-access room with 
limited access and on secure servers, also with limited access. In addition, subjects will be identified 
in the database by a study number and links to specific identifiers will be kept in a separate secure 
location. Database files will be maintained on a password protected computer in a secure location 
and backed up remotely.  
Benefits 
Subjects may or may not benefit from being in this study.  Because of the possibility of getting more 
tissue with the larger needle, subjects may be able to avoid further testing that may have been 
necessary if the smaller needle only was used. 
 
We hope the information learned will help other patients undergoing EBUS-TBNA for enlarged 
lymph nodes in the future. 
 
7. Data Confidentiality and Privacy 
All reports and study materials will be identified only by a subject identification number to maintain 
subject confidentiality. Tissue samples obtained through the procedure will be identified as per 
standard procedure for Regions Hospital. These tissue samples will not be retained in any way 
outside of standard protocol and will not be labeled with the subject’s study ID number. A master 
database linking the patient name & MRN will be maintained on a secure, password protected 
server in the CCRC. The CCRC uses a secure, electronic system that is currently used at Regions 
Hospital and is approved by IS&T Security. Any paper case report forms will be stored in locked file 
cabinets in the CCRC. The CCRC is a locked, protected department with limited badge access for 
security purposes.  
 
8. Timeline 
Submission  
 
 
 
 
April 2018 
Review and Approval  
 
 
 
April-May 2018 
Training  
 
 
 
 
 
May 2018 
Data Collection 
 
 
 
 
June 2018-February 2019 
Data Analysis  
 
 
 
 
March-April 2019 
Manuscript Preparation and Submission 
 
May-June 2019 
 
9. Dissemination/Sharing Results/Integration and Impact 
We will submit results to an appropriate academic meeting, such as the Society for Critical Care 
Medicine and plan to publish the results in a journal targeting critical care medicine, i.e. Journal of 
Critical Care or Critical Care Medicine. We plan to disseminate results both throughout Regions and 

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the greater organization. This will include departmental and leadership meetings with the 
departments participating in this research.  
 
10. References 
1. 
Detterbeck, F.C., et al., Executive Summary: Diagnosis and management of lung cancer, 3rd ed: 
American College of Chest Physicians evidence-based clinical practice guidelines. Chest, 2013. 
143(5 Suppl): p. 7S-37S. 
2. 
Wahidi, M.M., et al., Technical Aspects of Endobronchial Ultrasound-Guided Transbronchial 
Needle Aspiration: CHEST Guideline and Expert Panel Report. Chest, 2016. 149(3): p. 816-35. 
3. 
Hsu, L.H., et al., Comparison of 19-gauge eXcelon and WANG MW-319 transbronchial aspiration 
needles. Thorac Cancer, 2016. 7(2): p. 264-70. 
4. 
Biswas, A., et al., Comparison of the yield of 19-G eXcelon core needle to a 21-G EBUS needle 
during endobronchial ultrasound guided transbronchial needle aspiration of mediastinal lymph 
nodes for the detection of granulomas in cases of suspected sarcoidosis. J Thorac Dis, 2017. 9(9): 
p. E864-E866. 
5. 
Gnass, M., et al., Initial Polish experience of Flexible 19 gauge Endobronchial Ultrasound-Guided 
Transbronchial Needle Aspiration. Adv Respir Med, 2017. 85(2): p. 64-68. 
6. 
Herath, S. and W.A. Cooper, The novel 19G endobronchial USS (EBUS) needle samples processed 
as tissue "core biopsies" facilitate PD-L1 and other biomarker testing in lung cancer specimens: 
case report and the view point from the Respiratory Physician and the Pathologist. Respirol Case 
Rep, 2017. 5(6): p. e00271. 
7. 
Trisolini, R., et al., Endobronchial ultrasound-guided transbronchial needle aspiration with the 
flexible 19-gauge needle. Clin Respir J, 2017. 
8. 
Tyan, C., et al., Flexible 19-Gauge Endobronchial Ultrasound-Guided Transbronchial Needle 
Aspiration Needle: First Experience. Respiration, 2017. 94(1): p. 52-57. 
9. 
Silvestri, G.A., et al., Methods for staging non-small cell lung cancer: Diagnosis and management 
of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice 
guidelines. Chest, 2013. 143(5 Suppl): p. e211S-e250S.