CASEII: Cytosponge Adequacy Study Evaluation II

• Sponsor: Medtronic - MITG (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02395471
• Collaborator: (none)
• Enrollment: 191
• Locations: 5
• Arms: 2
• Duration (Months): 34
• Patients Per Site: 38.2
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

This study will assess the Minimally Invasive Esophageal Cytology Collection System in Patients with Barrett's Esophagus or GERD Symptoms.

Condition or Disease	Intervention/Treatment	Phase
Barrett's Esophagus; GERD	Device: Cytosponge™ Cell Collection Device	N/A

Detailed Description

This is a cross-sectional study of subjects with Barrett's esophagus (BE) to assess the utility of the Cytosponge device as a non-endoscopic method for collecting surface cells from the esophagus. This study will enroll 2 groups of subjects: 1) Subjects presenting for routine endoscopic BE surveillance examinations (n=120), and 2) Subjects with gastroesophageal reflux disease (GERD) symptoms undergoing upper endoscopy for screening for BE (n=55). After informed consent, and on the same day as the endoscopic procedure, the subject will undergo administration of the Cytosponge device and complete a questionnaire. The subject will then undergo routine upper endoscopy, with assessment of BE (where applicable), and biopsy per accepted surveillance or screening recommendations. The Cytosponge will be placed in fixative and shipped to an accredited pathology laboratory for embedding in paraffin and hematoxylin and eosin (H&E) staining to assess the adequacy of the specimen. Further evaluation of the specimen may be performed using trefoil factor 3 (TFF3). If the Cytosponge tissue specimen is inadequate, the subject will be recalled for a repeat sponge procedure (not endoscopy) 30 days later. Routine care tissue biopsies will undergo standard processing and H&E staining at the home institution, with assessment by expert gastrointestinal pathologists. Subjects will be contacted via phone 7 days (+/- 2 days) after Cytosponge administration to complete additional questionnaires and assess adverse events.

Study Design

• Study Type: Interventional
• Actual Enrollment: 191 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Assessment of a Minimally Invasive Esophageal Cytology Collection System in Patients With Barrett's Esophagus or GERD Symptoms
• Study Start Date: Aug 1, 2015
• Actual Primary Completion Date: Apr 24, 2018
• Actual Study Completion Date: Jun 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Patient wth Barrett's Subjects presenting for routine endoscopic BE surveillance examinations	Device: Cytosponge™ Cell Collection Device; Cytosponge™ Cell Collection Device is indicated for use in the collection and retrieval of surface cells in the esophagus.
Experimental: Patients with GERD Subjects with gastroesophageal reflux disease (GERD) symptoms undergoing upper endoscopy for screening for BE	Device: Cytosponge™ Cell Collection Device; Cytosponge™ Cell Collection Device is indicated for use in the collection and retrieval of surface cells in the esophagus.

Outcome Measures

Primary Outcome Measures

1. Procedure Preference and Acceptability Questionnaire and Visual Analog Scale [Immediately post procedure up to 7 days +/- 3 days]

   The first primary objective of the study was to assess the acceptability of a novel, minimally invasive esophageal mucosal sampling technique, the Cytosponge™, in subjects undergoing surveillance of BE who have had at least a C1 or M3 segment confirmed, and 2) in subjects with GERD undergoing screening for BE. This includes measures of acceptability as demonstrated on the Impact of Event Scale, a Visual Analog Scale for Pain, and the subject's willingness to undergo repeat Cytosponge™ administration if it were offered to him/her. The Visual Analog Scale is measured from 0-100 scale for pain, 0 representing no pain and 100 representing the highest level of pain.

2. Number of Participants With Adequate Cytosponge™ Sample [Immediately post procedure up to 7 days +/- 3 days]

   To assess the adequacy of cytology samples obtained by Cytosponge in this population after 1 sampling, and after 2 samplings if first sample inadequate.

Secondary Outcome Measures

1. Operating Characteristics [Immediately post procedure up to 7 days +/- 3 days]

   The operating characteristics of this technique against a gold standard of upper endoscopy with biopsies for endoscopic surveillance in subjects with BE who demonstrate an adequate sample on Cytosponge assessment.

2. Cytosponge™ Operating Characteristics vs Worst Histology Ever [Immediately post procedure up to 7 days +/- 3 days]

   The second secondary objective was to assess the operating characteristics of Cytosponge™ against the worst ever histology documented in the subject.

3. Cytosponge™ Operating Characteristics as a Function of Baseline Histology [Immediately post procedure up to 7 days +/- 3 days]

   The third secondary objective was to assess the operating characteristics of Cytosponge™ as a function of baseline histology. At the outset of this study, no data was available regarding the accuracy of TFF3 in samples collected by Cytosponge™ in subjects with BE and more advanced disease (low-grade dysplasia and high-grade dysplasia). These subjects are at greatest risk for progression to cancer. We planned to collect pilot data on operating characteristics of the assay by degree of baseline dysplasia. We hypothesized that TFF3 would perform with similar operating characteristics in this group compared to non-dysplastic BE.

4. Summary of Abrasion, Bleeding, and Perforation Observed Via Endoscopy [Immediately post procedure up to 7 days +/- 3 days]

   The fourth secondary objective was to assess the degree of mucosal abrasion following Cytosponge™ administration, using a standardized scale. The incidence is presented in the data below for abrasion, bleeding and perforation observed during Endoscopy.

5. Ongoing Safety Measures [Immediately post procedure up to 7 days +/- 3 days]

   To collect and analyze ongoing safety measures of Cytosponge use in the target population.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Male or female subjects, age 18 and above.

2. Able to read, comprehend, and complete the consent form.

3. Clinically fit for an endoscopy.

4. 1. Previous confirmed diagnosis of Barrett's esophagus with intestinal metaplasia, and Prague classification of at least one circumferential centimeter of BE or a total BE segment length of at least 3 centimeters (C1+ or CXM3+) (BE arm) . OR b) If the subject does not have documented Prague Classification prior to screening, but the PI is convinced that the subject will meet the inclusion criteria based on previous documentation (for instance, mention of "long-segment BE," they may enroll the subject in the study at their discretion. The study upper endoscopy must confirm that the subject has C1+ or CXM3+ (BE arm). If (C1+ or CXM3+) is not observed at the time of study endoscopy, the subject may still be enrolled but not included in the data analysis with the BE cohort. The data may be analyzed in a separate cohort. OR c) Self-reported heartburn or regurgitation on at least a monthly basis for at least 6 months (GERD arm).

Exclusion Criteria:

1. Individuals with a diagnosis of an oropharynx, esophageal or gastro-esophageal tumor, or symptoms of dysphagia.

2. Any history of esophageal varices, stricture, or prior dilation of the esophagus.

3. Current use of anti-thrombotics (anti-coagulants and anti-platelet drugs) that cannot be safely discontinued for the appropriate drug-specific interval in the peri-administration period. Depending on the particular agent or reason for the anti-thrombotic therapy, it may not be necessary to discontinue anti-thrombotic agents. There could be circumstances where the drug may not need to be discontinued if the risk of bleeding is considered negligible (e.g. daily aspirin therapy). Physicians should use their clinical judgement and should consult guidelines such as those provided by the ASGE.

4. Known bleeding disorder.

5. Individuals who have had a myocardial infarction or any cardiac event < 6 months prior to enrollment.

6. Individuals who have had a cerebrovascular event < 6 months prior to enrollment in which swallowing was affected.

7. Prior ablative or resection therapy of the esophagus including radiofrequency ablation (RFA), photodynamic therapy (PDT), spray cryotherapy, endoscopic mucosal resection, and other ablation therapies.

8. Any history of esophageal surgery, except for uncomplicated fundoplication.

9. Do not need upper endoscopy as part of patient management.

10. Pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Univeristy of California, Los Angeles	Los Angeles	California	United States	90095
2	University of Colorado	Aurora	Colorado	United States	80045
3	Northwestern University	Chicago	Illinois	United States	60611
4	University of North Carolina	Chapel Hill	North Carolina	United States	27599-7080
5	Gastrointestinal Associates	Knoxville	Tennessee	United States	37909

Sponsors and Collaborators

• Medtronic - MITG

Investigators

• Study Director: Amanda Cafaro, BSN, Medtronic Clinical Research Director

Study Documents (Full-Text)

• Study Protocol - Dec 1, 2017
• Statistical Analysis Plan - Aug 20, 2018

More Information

Publications

None provided.

• Responsible Party: Medtronic - MITG
• ClinicalTrials.gov Identifier: NCT02395471
• Other Study ID Numbers: B-271
• First Posted: Mar 23, 2015
• Last Update Posted: Jul 30, 2019
• Last Verified: Jul 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Barrett Esophagus

Study Results

Participant Flow

Arm/Group Title	Patient Wth Barrett's	Patients With GERD
Arm/Group Description	Subjects presenting for routine endoscopic BE surveillance examinations Cytosponge™ Cell Collection Device: Cytosponge™ Cell Collection Device is indicated for use in the collection and retrieval of surface cells in the esophagus.	Subjects with gastroesophageal reflux disease (GERD) symptoms undergoing upper endoscopy for screening for BE Cytosponge™ Cell Collection Device: Cytosponge™ Cell Collection Device is indicated for use in the collection and retrieval of surface cells in the esophagus.
Period Title: Overall Study
STARTED	129	62
COMPLETED	122	59
NOT COMPLETED	7	3

Baseline Characteristics

Arm/Group Title	Patient Wth Barrett's	Patients With GERD	Total
Arm/Group Description	Subjects presenting for routine endoscopic BE surveillance examinations Cytosponge™ Cell Collection Device: Cytosponge™ Cell Collection Device is indicated for use in the collection and retrieval of surface cells in the esophagus.	Subjects with gastroesophageal reflux disease (GERD) symptoms undergoing upper endoscopy for screening for BE Cytosponge™ Cell Collection Device: Cytosponge™ Cell Collection Device is indicated for use in the collection and retrieval of surface cells in the esophagus.	Total of all reporting groups
Overall Participants	129	62	191
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64 (10.4)	54.2 (15.1)	60.8 (12.9)
Sex: Female, Male (Count of Participants)
Female	36 27.9%	39 62.9%	75 39.3%
Male	93 72.1%	23 37.1%	116 60.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 1.6%	4 6.5%	6 3.1%
Not Hispanic or Latino	127 98.4%	57 91.9%	184 96.3%
Unknown or Not Reported	0 0%	1 1.6%	1 0.5%
Race/Ethnicity, Customized (Count of Participants)
American Indian Or Alaska Native	0 0%	1 1.6%	1 0.5%
Asian	1 0.8%	2 3.2%	3 1.6%
Black or African American	0 0%	5 8.1%	5 2.6%
Native Hawaiian or Other Pacific Islander	0 0%	1 1.6%	1 0.5%
White	127 98.4%	52 83.9%	179 93.7%
Other	1 0.8%	2 3.2%	3 1.6%

Outcome Measures

1. Primary Outcome

Title	Procedure Preference and Acceptability Questionnaire and Visual Analog Scale
Description	The first primary objective of the study was to assess the acceptability of a novel, minimally invasive esophageal mucosal sampling technique, the Cytosponge™, in subjects undergoing surveillance of BE who have had at least a C1 or M3 segment confirmed, and 2) in subjects with GERD undergoing screening for BE. This includes measures of acceptability as demonstrated on the Impact of Event Scale, a Visual Analog Scale for Pain, and the subject's willingness to undergo repeat Cytosponge™ administration if it were offered to him/her. The Visual Analog Scale is measured from 0-100 scale for pain, 0 representing no pain and 100 representing the highest level of pain.
Time Frame	Immediately post procedure up to 7 days +/- 3 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Participant Cytosponge Procedure Acceptability
Arm/Group Description	Acceptability of the Cytosponge Procedure by all study subjects that underwent both Cytosponge and Endoscopy
Measure Participants	191
On scale of 0-10 (10-high), rate Cytosponge exper.	7.2 (2.5)
On scale of 0-10 (10-high), rate endoscopy exper.	8.5 (2.5)
Diff. between the two scales: (Cyto/Endoscop)	-1.3 (2.4)
Visual Analog Scale	16.2 (18.3)

2. Primary Outcome

Title	Number of Participants With Adequate Cytosponge™ Sample
Description	To assess the adequacy of cytology samples obtained by Cytosponge in this population after 1 sampling, and after 2 samplings if first sample inadequate.
Time Frame	Immediately post procedure up to 7 days +/- 3 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patient Wth Barrett's	Patients With GERD
Arm/Group Description	Subjects presenting for routine endoscopic BE surveillance examinations Cytosponge™ Cell Collection Device: Cytosponge™ Cell Collection Device is indicated for use in the collection and retrieval of surface cells in the esophagus.	Subjects with gastroesophageal reflux disease (GERD) symptoms undergoing upper endoscopy for screening for BE Cytosponge™ Cell Collection Device: Cytosponge™ Cell Collection Device is indicated for use in the collection and retrieval of surface cells in the esophagus.
Measure Participants	127	61
Count of Participants [Participants]	115 89.1%	56 90.3%

3. Secondary Outcome

Title	Operating Characteristics
Description	The operating characteristics of this technique against a gold standard of upper endoscopy with biopsies for endoscopic surveillance in subjects with BE who demonstrate an adequate sample on Cytosponge assessment.
Time Frame	Immediately post procedure up to 7 days +/- 3 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Operating Characteristics of Cytosponge™/TFF3 vs BE Diagnosis
Arm/Group Description	Sensitivity, Specificity, PPV, NPV, and Accuracy of Cytosponge™/TFF3 vs. the Gold Standard of Endoscopy for BE Diagnosis
Measure Participants	154
Sensitivity	75.5
Specificity	76.7
Positive Predictive Value	83.5
Accuracy	76

4. Secondary Outcome

Title	Cytosponge™ Operating Characteristics vs Worst Histology Ever
Description	The second secondary objective was to assess the operating characteristics of Cytosponge™ against the worst ever histology documented in the subject.
Time Frame	Immediately post procedure up to 7 days +/- 3 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cytosponge™ Operating Characteristics vs Worst Histology
Arm/Group Description	The second secondary objective was to assess the operating characteristics of Cytosponge™ against the worst ever histology documented in the subject.
Measure Participants	158
Sensitivity	77
Specificity	81
Positive Predictive Value	87.5
Negative Predictive Value	67.1
Accuracy	78.5

5. Secondary Outcome

Title	Cytosponge™ Operating Characteristics as a Function of Baseline Histology
Description	The third secondary objective was to assess the operating characteristics of Cytosponge™ as a function of baseline histology. At the outset of this study, no data was available regarding the accuracy of TFF3 in samples collected by Cytosponge™ in subjects with BE and more advanced disease (low-grade dysplasia and high-grade dysplasia). These subjects are at greatest risk for progression to cancer. We planned to collect pilot data on operating characteristics of the assay by degree of baseline dysplasia. We hypothesized that TFF3 would perform with similar operating characteristics in this group compared to non-dysplastic BE.
Time Frame	Immediately post procedure up to 7 days +/- 3 days

Outcome Measure Data

Analysis Population Description

Among study subjects with BE that exhibited HGD, there were no true negatives or false positives, therefore specificity of the assay was not calculated for this subgroup.

Arm/Group Title	Non-Dysplastic BE	Indefinite for Dysplasia	Low Grade Dysplasia	High Grade Dysplasia
Arm/Group Description	Non-Dysplastic BE	Indefinite for Dysplasia	Low Grade Dysplasia	High Grade Dysplasia
Measure Participants	77	13	10	6
Sensitivity	76.2	66.7	77.8	83.3
Specificity	64.3	100	0	NA
Accuracy	74.0	69.2	70.0	83.3

6. Secondary Outcome

Title	Summary of Abrasion, Bleeding, and Perforation Observed Via Endoscopy
Description	The fourth secondary objective was to assess the degree of mucosal abrasion following Cytosponge™ administration, using a standardized scale. The incidence is presented in the data below for abrasion, bleeding and perforation observed during Endoscopy.
Time Frame	Immediately post procedure up to 7 days +/- 3 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Incidence
Arm/Group Description	Incidence of Abrasion, Bleeding and Perforation observed via Endoscopy
Measure Participants	190
Abrasion	117 90.7%
Bleeding	58 45%
Bleeding-From Cytosponge contact site	14 10.9%
Bleeding-From Biopsy Site	56 43.4%
Perforation	0 0%
Any of These 3 Conditions	141 109.3%

7. Secondary Outcome

Title	Ongoing Safety Measures
Description	To collect and analyze ongoing safety measures of Cytosponge use in the target population.
Time Frame	Immediately post procedure up to 7 days +/- 3 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Incidence of AE's
Arm/Group Description	Incidence of AE's
Measure Participants	14
Not Coded	3 2.3%
Dyspepsia	1 0.8%
Vomiting	1 0.8%
Chest Discomfort	1 0.8%
Device Breakage	2 1.6%
Oropharyngeal Pain	4 3.1%
Throat Irritation	2 1.6%

Adverse Events

Time Frame	Subjects will be contacted 7 days (+/- 2 days) following the Cytosponge and upper endoscopy procedures. During this phone call, adverse events will be assessed and subjects will complete questionnaires. Participation in the study is complete when subjects have completed the follow-up phone call.
Arm/Group Title	Patient Wth Barrett's		Patients With GERD
Arm/Group Description	Subjects presenting for routine endoscopic BE surveillance examinations who had at least a C1 or M3 segment confirmed (or medically suspected). Cytosponge™ Cell Collection Device: Cytosponge™ Cell Collection Device is indicated for use in the collection and retrieval of surface cells in the esophagus.		Subjects with gastroesophageal reflux disease (GERD) symptoms undergoing screening for BE Cytosponge™ Cell Collection Device: Cytosponge™ Cell Collection Device is indicated for use in the collection and retrieval of surface cells in the esophagus.
All Cause Mortality
	Patient Wth Barrett's		Patients With GERD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/129 (0%)		0/62 (0%)
Serious Adverse Events
	Patient Wth Barrett's		Patients With GERD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/129 (1.6%)		0/62 (0%)
Product Issues
Sponge Detachment	2/129 (1.6%)	2	0/62 (0%)	0
Other (Not Including Serious) Adverse Events
	Patient Wth Barrett's		Patients With GERD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/129 (6.2%)		6/62 (9.7%)
Gastrointestinal disorders
Dyspepsia	0/129 (0%)	0	1/62 (1.6%)	1
Vomiting	0/129 (0%)	0	1/62 (1.6%)	1
General disorders
Chest Discomfort	1/129 (0.8%)	1	0/62 (0%)	0
Investigations
Not Coded	2/129 (1.6%)	2	1/62 (1.6%)	1
Product Issues
Device Breakage	2/129 (1.6%)	2	0/62 (0%)	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	2/129 (1.6%)	2	2/62 (3.2%)	2
Throat Irritation	1/129 (0.8%)	1	1/62 (1.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.