Trial Title:
Seattle Biopsy Protocol Versus Wide-Area Transepithelial Sampling in Patients With Barrett's Esophagus Undergoing Surveillance
NCT ID:
NCT05530343
Condition:
Barrett Esophagus
Barretts Esophagus With Dysplasia
Esophageal Adenocarcinoma
Conditions: Official terms:
Adenocarcinoma
Barrett Esophagus
Conditions: Keywords:
Barrett's Esophagus
Esophageal Adenocarcinoma
Dysplasia
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Crossover Assignment
Primary purpose:
Screening
Masking:
Single (Outcomes Assessor)
Intervention:
Intervention type:
Diagnostic Test
Intervention name:
Seattle protocol
Description:
Participants undergo 4-quadrant biopsies with standard biopsy forceps taken at 2 cm
intervals. For participants undergoing a confirmatory endoscopy for cases in which
discordant results are noted (WATS3D positive for dysplasia/cancer and Seattle biopsy
negative for dysplasia/cancer), repeat biopsies will be taken at 1 cm intervals along
with target biopsies from any visible lesions.
Arm group label:
Seattle protocol, then WATS3D brushings.
Arm group label:
WATS3D brushings, then Seattle Protocol.
Intervention type:
Diagnostic Test
Intervention name:
WATS3D brushings
Description:
Participants undergo 2 WATS3D biopsies of every 5 cm segment of Barrett's esophagus,
starting from the gastroesophageal junction and moving proximally through the entire
segment of Barrett's.
Arm group label:
Seattle protocol, then WATS3D brushings.
Arm group label:
WATS3D brushings, then Seattle Protocol.
Summary:
The purpose of this research study is to learn about the best approach to sample patients
with known or suspected Barrett's esophagus (BE) by comparing the standard Seattle biopsy
protocol to sampling using wide area transepithelial sampling (WATS3D).
Barrett's esophagus is a common condition that is used to spot patients at increased risk
of developing a type of cancer in the esophagus (swallowing tube) called esophageal
adenocarcinoma. The 5-year survival rate is as low as 18% for patients who get esophageal
adenocarcinoma, but the rate may be improved if the cancer is caught in its early stages.
Barrett's esophagus can lead to dysplasia, or precancerous changes, which occurs when
cells look abnormal but have not developed into cancer. If the abnormal cells increase
from being slightly abnormal (low-grade dysplasia), to being very abnormal (high-grade
dysplasia), the risk of developing cancer (esophageal adenocarcinoma) goes up. Therefore,
catching dysplasia early is very important to prevent cancer.
Endoscopic surveillance is a type of procedure where endoscopists run a tube with a light
and a camera on the end of it down a patients throat and remove a small piece of tissue.
The piece of tissue, called a biopsy, is about the size of the tip of a ball-point pen
and is checked for abnormal cells and cancer cells.
Patients are being asked to be in this research study because they have been diagnosed
with BE or suspected to have BE, and will need an esophagogastroduodenoscopy (EGD).
Patients with BE undergo sampling using the Seattle biopsy protocol during which samples
are obtained from the BE in a four quadrant fashion every 2 cm along with target biopsies
from any abnormal areas within the BE. Another sampling approach is WATS3D which utilizes
brushings from the BE.
While both of these procedures are widely accepted approaches to sampling patients with
BE during endoscopy, there is not enough research to show if one is better than the
other.
Participants in this study will undergo sampling of the BE using both approaches (Seattle
biopsy protocol and WATS-3D); the order of the techniques will be randomized.
Up to 2700 participants will take part in this research. This is a multicenter study
involving several academic, community and private hospitals around the country.
Detailed description:
Methodology:
Patients with non-dysplastic Barrett's esophagus (BE) undergoing surveillance and
patients meeting criteria for screening for BE with columnar-lined esophagus detected at
endoscopy will be recruited in this multicenter randomized controlled trial.
All patients will undergo upper endoscopy using high-definition white light endoscopy and
electronic chromoendoscopy (NBI/FICE). The findings (detection of visible
lesions/abnormal mucosal or vascular pattern) with electronic chromoendoscopy will be
recorded.
Patients will be randomized to receive sampling using either the Seattle biopsy protocol
or WATS3D. The Seattle protocol will entail obtaining random biopsies every 2 cm in a
4-quadrant fashion. Biopsies will be taken from any visible lesion (no matter how subtle)
and will be submitted in separate jars and excluded from the comparative analysis of the
study. The WATS3D procedure will be conducted using a standardized protocol. Patients
will then receive sampling using the technique to which they were not assigned to by
randomization. This allows for all patients to receive standard of care (sampling using
the Seattle biopsy protocol), and to determine concordance between the two sampling
techniques acknowledging that one sampling technique could potentially affect the results
of other sampling technique.
In patients with discordant results (WATS3D positive and random biopsy negative), repeat
upper endoscopy with sampling using the Seattle biopsy protocol will be performed in an
attempt to confirm the findings noted at WATS3D. This will be performed in the
surveillance and screening population. Biopsy specimens will be submitted for
histopathologic examination for routine clinical care. For the purpose of this study, all
biopsy specimens will be sent to the Cleveland Clinic for interpretation by a central GI
pathologist who will be blinded to patient details and to reading by the WATS3D
pathologist.
Study Duration:
Interventions performed as described above will be performed during one endoscopic
procedure. The endpoints in this study will include progression to dysplasia, cancer,
need for endoscopic eradication therapy, and death.
Planned enrollment period: 2.5 years. Planned duration of the study: 3 years.
Study Centers:
To maximize the generalizability of results, this randomized controlled trial will be
conducted across different practice settings that include tertiary care centers, closed
healthcare networks and large community practices at approximately 14 sites.
Anticipated Number of Participants:
2298 (see Statistical Methodology below)
- 1982 to compare diagnostic yield of dysplasia between the two approaches in BE
patients undergoing surveillance
- 316 to compare diagnostic yield of intestinal metaplasia between the two approaches
in patients undergoing screening for BE
Statistical Methodology:
For a prospective randomized trial in detecting LGD, HGD or EAC comparing the Seattle
protocol, the current standard practice, to wide-area transepithelial sampling (WATS3D)
where all positive results for dysplasia or EAC with WATS3D sampling not detected on
Seattle biopsy protocol at index endoscopy will require confirmation by repeat sampling
using the Seattle biopsy protocol at repeat endoscopy, the following sample sizes were
calculated assuming α=0.05 and power of 0.8. All calculations are completed using PROC
POWER in SAS 9.4 for Fisher's exact test unless otherwise noted.
For the primary aim (surveillance population), the investigators will compare the
proportion of positive results between the Seattle protocol and WATS3D where all positive
results for dysplasia or EAC with WATS3D sampling not detected on Seattle biopsy protocol
at index endoscopy will require confirmation by repeat sampling using the Seattle biopsy
protocol at repeat endoscopy with either Pearson's chi-square test or Fisher's exact test
for proportions. Positive findings of dysplasia or EAC on WATS not detected on Seattle
biopsy protocol at index endoscopy or subsequent repeat endoscopy with sampling using the
Seattle biopsy protocol will not be considered as dysplasia or EAC detected by WATS for
the primary analysis. Previous pooled estimates indicated a 2.5% detection rate with
Seattle protocol and 4.9% with WATS3D, resulting in a need for 828 participants for each
arm (a total of 1656). However, the investigators are restricting to WATS3D cases which
are confirmed with target biopsy or Seattle protocol at the initial visit or a follow-up
sample when results are discordant. Assuming a 95% confirmation rate, 991 participants
are need for each arm to compare a 2.5% detection rate for Seattle protocol and 4.655%
for WATS3D (a total of 1982).
For the primary aim (screening population), the investigators will compare the proportion
of positive results between techniques to which patients are randomized with Fisher's
exact test for proportions. Previous pooled estimates indicated a 40% intestinal
metaplasia detection rate with Seattle protocol and 60% with WATS3D. However, the
investigators are restricting to WATS3D cases which are confirmed with target biopsy or
Seattle protocol at the initial visit or a follow-up sample when results are discordant.
Assuming a 95% confirmation rate, 158 participants are need for each arm to compare a 40%
detection rate for Seattle protocol and 57% for WATS3D (a total of 316).
The investigators will conduct one interim analysis using Lan and DeMet's alpha spending
function approximating O'Brien-Fleming boundaries. Based the sample size estimates above,
the investigators expect the interim analysis will occur after the data for 991
participants (50% enrollment) has been collected. This interim analysis will be
restricted to the primary aim in the surveillance population. No interim analysis will be
conducted to address the primary aim in the screening population. In the case where study
enrollment does not stop early due to efficacy, all participating physicians will be
blinded to the results of this interim analysis.
As a secondary analysis, the investigators will use results from both the randomized
procedure and the follow-up procedure with the protocol to which patients were not
randomized to perform a paired analysis of the concordance between the two diagnostic
tests. Although an important analysis for determining whether WATS3D could be used
instead of the Seattle protocol, due to the risk of the initial biopsy affecting these
results of the follow up procedure this is a secondary analysis. Given the sample size of
1982 for the primary outcome, there is greater than 99.9% power to detect a difference in
the paired results between proposed discordant proportions of 0.3575% for Seattle
protocol positive and WATS3D negative to 3.11% for WATS3D positive and Seattle protocol
negative using McNemar's test for paired nominal data. These discordant proportion
estimates are derived from prior pooled data for dysplasia detection rates of 4.9% for
WATS3D alone and 2.5% for Seattle protocol alone, with the discordant proportions of test
results derived from data reported in Vennalaganti assuming that only 80% of WATS3D
positive and Seattle protocol negative cases are verified with targeted follow-up
biopsies to confirm the diagnosis.
The comparison of yield of dysplasia will also be conducted based on expert pathology
review for biopsy and WATS3D specimens. The overall proportion of cases with visible
lesions with their associated pathology results will be recorded and will not be a part
of the analyses comparing the diagnostic yield of dysplasia between the Seattle biopsy
protocol with WATS3D.
The primary outcome comparing diagnostic yield of any dysplasia and intestinal metaplasia
between the two randomized arms will use either Pearson's chi-square or Fisher's exact
test for portions. The secondary analysis for paired data will use McNemar's test and
will exclude cases that were WATS3D positive but could not be confirmed by a concurrent
(Seattle protocol) or follow-up endoscopic biopsies using the Seattle biopsy protocol. A
sensitivity analysis will be completed which includes WATS3D positive cases that did not
have diagnostic confirmation with biopsy. Comparison for the detection of intestinal
metaplasia between the two strategies will use McNemar's test for paired data including
all cases.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Surveillance Population
- Undergoing surveillance endoscopy for a diagnosis of non-dysplastic Barrett's
esophagus (NDBE, based on last endoscopic procedure; patients with prior history of
low-grade dysplasia/indefinite for dysplasia with NDBE at last endoscopy can be
included)
- Barrett's esophagus (BE) length of at least M1
- English and Spanish speaking
- Able to comprehend and complete the consent form
- Age18-89 years
- Life-expectancy of at least 2 years
Screening Population
- Undergoing endoscopy for screening of BE
- BE length of at least M1
- English and Spanish speaking
- Able to comprehend and complete the consent form
- Age 18-89 years
- Expected life-expectancy of at least 2 years
Physicians
-All participating sites will include physicians who are trained in the use of WATS3D and
certified by the site PI. All endoscopists will need to complete a minimum of three cases
to be eligible to participate in the study.
Exclusion Criteria:
Surveillance Population
- BE patients undergoing surveillance or evaluation for endoscopic eradication therapy
(EET) for prior diagnosis of BE related dysplasia or esophageal adenocarcinoma (EAC)
- Active erosive esophagitis with LA Grade B or higher
- Esophageal varices
- Prior history of EET
- Prior history of esophageal or gastric surgery, except for uncomplicated
fundoplication
- Pregnancy
Screening Population
- BE patients undergoing surveillance or evaluation for EET for prior diagnosis for
BE-related dysplasia or EAC
- Active erosive esophagitis with LA Grade B or higher
- Esophageal varices
- Prior history of esophageal or gastric surgery, except for uncomplicated
fundoplication
- Pregnancy
Gender:
All
Minimum age:
18 Years
Maximum age:
89 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Arizona Centers of Digestive Health
Address:
City:
Gilbert
Zip:
85295
Country:
United States
Status:
Recruiting
Contact:
Last name:
Mankanwal Sachdev, MD
Email:
msachdev@azcdh.com
Investigator:
Last name:
Mankanwal Sachdev, MD
Email:
Principal Investigator
Investigator:
Last name:
Virender Sharma, MD
Email:
Sub-Investigator
Facility:
Name:
UCLA / Jonsson Comprehensive Cancer Center
Address:
City:
Los Angeles
Zip:
90024
Country:
United States
Status:
Recruiting
Contact:
Last name:
Raman Muthusamy, MD
Email:
raman@mednet.ucla.edu
Contact backup:
Phone:
310-825-1892
Investigator:
Last name:
Venkataraman Muthusamy, MD
Email:
Principal Investigator
Investigator:
Last name:
Adarsh M Thaker, MD
Email:
Sub-Investigator
Investigator:
Last name:
Kevin A Ghassemi, MD
Email:
Sub-Investigator
Facility:
Name:
Kaiser Permanente
Address:
City:
Oakland
Zip:
94611
Country:
United States
Status:
Recruiting
Contact:
Last name:
Howard Chang, MD
Email:
howard.y.chang@kp.org
Investigator:
Last name:
Howard Chang, MD
Email:
Principal Investigator
Investigator:
Last name:
Gene Ma, MD
Email:
Sub-Investigator
Investigator:
Last name:
Mitchell Liverant, MD
Email:
Sub-Investigator
Facility:
Name:
University of Colorado Anschutz Medical Campus
Address:
City:
Aurora
Zip:
80045
Country:
United States
Status:
Recruiting
Contact:
Last name:
Alexa DeBord, MS
Phone:
303-724-0432
Email:
alexa.debord@cuanschutz.edu
Contact backup:
Last name:
Sandra Boimbo, MPH
Phone:
303-724-8892
Email:
sandra.boimbo@cuanschutz.edu
Investigator:
Last name:
Sachin Wani, MD
Email:
Principal Investigator
Investigator:
Last name:
Steven Edmundowicz, MD
Email:
Sub-Investigator
Investigator:
Last name:
Mihir Wagh, MD
Email:
Sub-Investigator
Investigator:
Last name:
Paul Menard-Katcher, MD
Email:
Sub-Investigator
Facility:
Name:
Connecticut Clinical Research Institute
Address:
City:
Bristol
Zip:
06010
Country:
United States
Status:
Recruiting
Contact:
Last name:
Salam Zakko, MD
Email:
szakko@connecticutgi.org
Investigator:
Last name:
Salam Zakko, MD
Email:
Principal Investigator
Investigator:
Last name:
Peter Bloom, MD
Email:
Sub-Investigator
Investigator:
Last name:
Liam Zakko, MD
Email:
Sub-Investigator
Investigator:
Last name:
Daniel Smiley, MD
Email:
Sub-Investigator
Investigator:
Last name:
Mark Versland, MD
Email:
Sub-Investigator
Investigator:
Last name:
Eddy Castillo, MD
Email:
Sub-Investigator
Investigator:
Last name:
David Chaletsky, MD
Email:
Sub-Investigator
Facility:
Name:
Suncoast Endoscopy of Sarasota
Address:
City:
Sarasota
Zip:
34239
Country:
United States
Status:
Recruiting
Contact:
Last name:
Scott Corbett, MD
Phone:
941-320-7327
Email:
scott.corbett@FDHS.com
Contact backup:
Last name:
Lisa Underwood
Phone:
941-952-1145
Phone ext:
203
Email:
lunderwood@suncoastendoscopy.com
Investigator:
Last name:
Scott Corbett, MD
Email:
Principal Investigator
Facility:
Name:
Northwestern University
Address:
City:
Chicago
Zip:
60611
Country:
United States
Status:
Recruiting
Contact:
Last name:
Srinadh Komanduri, MD
Phone:
312-933-4873
Email:
sri-komanduri@northwestern.edu
Contact backup:
Last name:
Justeena Jojo
Phone:
312-926-4977
Email:
justeena.jojo@northwestern.edu
Investigator:
Last name:
Srinadh Komanduri, MD
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Recruiting
Contact:
Last name:
Prasad Iyer, MD
Phone:
507-266-4338
Email:
iyer.prasad@mayo.edu
Contact backup:
Last name:
Melissa Passe
Phone:
(507) 255-8693
Email:
passe.melissa@mayo.edu
Investigator:
Last name:
Prasad Iyer, MD
Email:
Principal Investigator
Investigator:
Last name:
Cadman Leggett, MD
Email:
Sub-Investigator
Investigator:
Last name:
Chamil Codipilly, MD
Email:
Sub-Investigator
Facility:
Name:
Long Island Jewish Medical Center
Address:
City:
New Hyde Park
Zip:
11040
Country:
United States
Status:
Recruiting
Contact:
Last name:
Molly Stewart, BS
Phone:
718-470-4667
Email:
Mstewart8@northwell.edu
Investigator:
Last name:
Arvind Trindade, MD
Email:
Principal Investigator
Facility:
Name:
Weill Cornell Medicine
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Felice Schnoll-Sussman, MD
Email:
fhs2001@med.cornell.edu
Investigator:
Last name:
Felice H Schnoll-Sussman, MD
Email:
Principal Investigator
Investigator:
Last name:
Philip O Katz, MD
Email:
Sub-Investigator
Investigator:
Last name:
Amir Soumekh, MD
Email:
Sub-Investigator
Facility:
Name:
University of Rochester
Address:
City:
Rochester
Zip:
14642
Country:
United States
Status:
Recruiting
Contact:
Last name:
Vivek Kaul, MD
Email:
vivek_kaul@urmc.rochester.edu
Investigator:
Last name:
Vivek Kaul, MD
Email:
Principal Investigator
Investigator:
Last name:
Shivangi Kothari, MD
Email:
Sub-Investigator
Facility:
Name:
University of North Carolina at Chapel Hill
Address:
City:
Chapel Hill
Zip:
27599
Country:
United States
Status:
Recruiting
Contact:
Last name:
Nicholas Shaheen, MD
Email:
nicholas_shaheen@med.unc.edu
Contact backup:
Last name:
Katie Danis
Phone:
(919) 843-5884
Investigator:
Last name:
Nicholas J Shaheen, MD
Email:
Principal Investigator
Investigator:
Last name:
Swathi Eluri, MD
Email:
Sub-Investigator
Investigator:
Last name:
Cary C Cotton, MD
Email:
Sub-Investigator
Facility:
Name:
Geisinger Medical Center
Address:
City:
Danville
Zip:
17822
Country:
United States
Status:
Recruiting
Contact:
Last name:
Harshit Khara, MD
Email:
hskhara@geisinger.edu
Investigator:
Last name:
Harshit Khara, MD
Email:
Principal Investigator
Investigator:
Last name:
Joshua Obuch, MD
Email:
Sub-Investigator
Facility:
Name:
Gastrointestinal Associates, PC
Address:
City:
Knoxville
Zip:
37909
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kathy Karnes, BSN, RN
Phone:
865-558-0687
Email:
kkarnes@gihealthcare.com
Investigator:
Last name:
John M Haydek, MD
Email:
Principal Investigator
Investigator:
Last name:
Raj I Narayani, MD
Email:
Sub-Investigator
Start date:
October 3, 2022
Completion date:
March 2026
Lead sponsor:
Agency:
University of Colorado, Denver
Agency class:
Other
Source:
University of Colorado, Denver
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05530343
